The following references were utilized by Prof. Dr. Frederick Carrick for his lecture on the Sensory Systems Module 11. Of interest to learners is the integration of the mesolimbic and substantianigral dominergic activating systems in concert with perception and sensory integration.
Prof. Dr. Carrick's reading requirements for the Sensory Systems Module are DeJong's Neurological Examination, Lippincott-Raven Chapters 5-8

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1. Alais, D.; van, der Smagt MJ; van, den Berg AV; van, de Grind WA. Local and global factors affecting the coherent motion of gratings presented in multiple apertures.
Vision-Res. 1998 Jun; 38(11): 1581-91; ISSN: 0042-6989.
ENGLAND. Using stimuli composed of two independent gratings viewed through multiple apertures, we investigate a number of parameters affecting the integration of locally ambiguous motions into globally coherent motion. In four experiments, we varied local factors (grating spatial frequency, speed, contrast, duty cycle, orientation) and global factors (degree of similarity and common fate between the gratings, and symmetry in the configuration of the grating pattern) and examined their effects on global motion coherence. Our results, confirming accounts offered by previous investigators, indicate that local competition between motion signals generated by contours (ambiguous) and their line terminations (unambiguous) is important in determining global motion coherence in multiple-aperture stimuli. Our results also indicate that global factors can affect perceived coherence independently of local motion signals, suggesting the involvement of higher-level motion areas and a role for non-motion processes such as those involved in pattern and form perception. Comparing motion coherence with other two-dimensional (2-D) stimuli (plaids) shows that 2-D multiple-aperture stimuli are not analogous and that coherence models derived from plaid stimuli do not account for the data.
3. Arden, G. B.; Wolf, J. E.; Tsang, Y. Does dark adaptation exacerbate diabetic retinopathy? Evidence and a linking hypothesis. Vision-Res. 1998 Jun; 38(11):
1723-9; ISSN: 0042-6989.
ENGLAND. The paper reviews evidence that before any change in diabetics' fundi, changes occur to blood flow, ERG and visual functions. In the case of colour vision and contrast sensitivity, the changes are partially reversed by breathing oxygen, and therefore are the result of retinal hypoxia. There are also other evidences that hypoxia is a major factor in the development of diabetic retinopathy (DR). Therefore in diabetics with early retinopathy, but normal photopic vision, functional disturbance might appear in dark adaptation, since in such circumstances, (as shown by Linsenmeier and his colleagues) the already low retinal PO2 markedly decreases. This hypothesis has been tested and results consistent with the hypothesis (and with a number of older reports) have been obtained. The significance of this finding to early DR is discussed, and a mechanism suggested whereby prolonged periods of hypoxia during dark adaptation could generate changes in retinal capillaries. Such periods occur each night, and their elimination in diabetics could be therapeutic.
4. Arden, G. B.; Wolf, J. E.; Tsang, Y. Does dark adaptation exacerbate diabetic retinopathy? Evidence and a linking hypothesis. Vision-Res. 1998 Jun; 38(11):
1723-9; ISSN: 0042-6989.
ENGLAND. The paper reviews evidence that before any change in diabetics' fundi, changes occur to blood flow, ERG and visual functions. In the case of colour vision and contrast sensitivity, the changes are partially reversed by breathing oxygen, and therefore are the result of retinal hypoxia. There are also other evidences that hypoxia is a major factor in the development of diabetic retinopathy (DR). Therefore in diabetics with early retinopathy, but normal photopic vision, functional disturbance might appear in dark adaptation, since in such circumstances, (as shown by Linsenmeier and his colleagues) the already low retinal PO2 markedly decreases. This hypothesis has been tested and results consistent with the hypothesis (and with a number of older reports) have been obtained. The significance of this finding to early DR is discussed, and a mechanism suggested whereby prolonged periods of hypoxia during dark adaptation could generate changes in retinal capillaries. Such periods occur each night, and their elimination in diabetics could be therapeutic.
5. Armstrong, D. G.; Hussain, S. K.; Middleton, J.; Peters, E. J.; Wunderlich, R. P.; Lavery, L. A. Vibration perception threshold: are multiple sites of testing superior to single site testing on diabetic foot examination? Ostomy-Wound-Manage. 1998
May; 44(5): 70-4, 76; ISSN: 0889-5899.
UNITED-STATES. Vibration perception threshold (VPT) values, measured at different anatomic locations on the foot and ankle, and the time to assess VPT and sensory perception using two difference modalities in 102 diabetic patients were compared. VPT was evaluated at the great toe, fifth metatarsal and ankle. Differences in VPT at these three sites, in addition to differences in duration of testing comparing single site (great toe) to multiple sites, and to standard SWMF testing were assessed. No significant difference in VPT between the great toe and fifth metatarsal was found for patients both with and without loss of protective sensation (LOPS). Mean VPT was significantly higher at the ankle compared with both the great toes and fifth metatarsals. However, the difference between ankle and great toe was not significant between patients with and without LOPS [3.9 +/- 11.2 (12%) vs. 3.0 +/- 10.8 (16%) volts, respectively, p > 0.6]. Testing of one site took approximately half the time of Semmes-Weinstein 10-gram monofilament wire SWMF testing (40.5 +/- 16.9 vs. 22.3 +/- 9.1 seconds, p < 0.01) and less than one third the time of three-site VPT testing (10.5 +/- 26.1 vs. 22.3 +/- 9.1 seconds, p < 0.01). There may not be a significant practical benefit in multiple site VPT testing when compared with single site testing on the great toe alone. The value of multiple site testing is further called into question when one notes that the great toe VPT remains the only site tested for sensitivity and specificity for ulceration.
6. Armstrong, D. G.; Hussain, S. K.; Middleton, J.; Peters, E. J.; Wunderlich, R. P.; Lavery, L. A. Vibration perception threshold: are multiple sites of testing superior to single site testing on diabetic foot examination? Ostomy-Wound-Manage. 1998
May; 44(5): 70-4, 76; ISSN: 0889-5899.
UNITED-STATES. Vibration perception threshold (VPT) values, measured at different anatomic locations on the foot and ankle, and the time to assess VPT and sensory perception using two difference modalities in 102 diabetic patients were compared. VPT was evaluated at the great toe, fifth metatarsal and ankle. Differences in VPT at these three sites, in addition to differences in duration of testing comparing single site (great toe) to multiple sites, and to standard SWMF testing were assessed. No significant difference in VPT between the great toe and fifth metatarsal was found for patients both with and without loss of protective sensation (LOPS). Mean VPT was significantly higher at the ankle compared with both the great toes and fifth metatarsals. However, the difference between ankle and great toe was not significant between patients with and without LOPS [3.9 +/- 11.2 (12%) vs. 3.0 +/- 10.8 (16%) volts, respectively, p > 0.6]. Testing of one site took approximately half the time of Semmes-Weinstein 10-gram monofilament wire SWMF testing (40.5 +/- 16.9 vs. 22.3 +/- 9.1 seconds, p < 0.01) and less than one third the time of three-site VPT testing (10.5 +/- 26.1 vs. 22.3 +/- 9.1 seconds, p < 0.01). There may not be a significant practical benefit in multiple site VPT testing when compared with single site testing on the great toe alone. The value of multiple site testing is further called into question when one notes that the great toe VPT remains the only site tested for sensitivity and specificity for ulceration.
7. Azzi, M.; Betancur, C.; Sillaber, I.; Spangel, R.; Rostene, W.; Berod, A. Repeated administration of the neurotensin receptor antagonist SR 48692 differentially regulates mesocortical and mesolimbic dopaminergic systems. J-Neurochem. 1998
Sep; 71(3): 1158-67; ISSN: 0022-3042.
UNITED-STATES. The purpose of the present study was to investigate the effects of repeated administration of the neurotensin receptor antagonist, SR 48692, on the activity of the mesocortical and mesolimbic dopaminergic (DA) systems. We showed that daily administration of SR 48692 for 15 days (1 mg/kg i.p.) to Wistar rats increased the expression of tyrosine hydroxylase mRNA and protein in the ventral mesencephalon. Simultaneous in vivo microdialysis in the shell part of the nucleus accumbens (AcbSh) and the medial prefrontal cortex (mPFC) revealed that blockade of neurotensin receptors for 15 days decreased basal extracellular levels of DA (approximately 50%) and its metabolites in the AcbSh, whereas no modification in DA levels was observed in the mPFC. In animals submitted to a forced swimming stress, which preferentially enhanced extracellular DA levels in the mPFC, treatment with SR 48692 failed to affect the stress-induced increase in DA. Moreover, given that glucocorticoids can modulate the activity of mesencephalic DA neurons, we examined the effect of the same SR 48692 treatment on corticosterone levels in dialysates from the AcbSh. We found that repeated SR 48692 did not affect the basal levels of free corticosterone, but significantly reduced the increase induced by forced swimming stress. The present results demonstrate that repeated treatment with SR 48692 modulates selectively the DA mesolimbic system when compared with the mesocortical pathway. These findings suggest that long-term treatment with selective neurotensin receptor antagonists could have potential clinical utility in the treatment of neuropsychiatric disorders associated with hyperactivity of the mesolimbic DA systems or the hypothalamic-pituitary-adrenal axis.. EC 1.14.16.2; 0; 0; 0; 0; 146362-70-1; 50-22-6; 51-61-6.
8. Behrendt, R. P. Underconstrained perception: a theoretical approach to the nature and
function of verbal hallucinations. Compr-Psychiatry. 1998 Jul; 39(4): 236-48;
ISSN: 0010-440X.
UNITED-STATES. We do not see the world as it is. Perception forms a
subjective image of the world in a language that has proven to be adaptive to our
interaction with the external world. Perception is mainly determined by current
needs of the organism and goals of behavior. Sensory processing itself does not
culminate in perception and is not essential for perception, since perception
derives from representations of internal symbols and their features. The current
stimulation of sensory organs does, however, constrain our perception.
Perception might be less constrained by the external world in cases of (1)
increased attention, (2) decreased sensory stimulation, or (3) facilitated formation
of cortical associations between representations of expectations and internal
symbols. Hallucinations are perceptions that are underconstrained by external
sensory stimulation. Verbal hallucinations that allow the patient to infer about his
self-image might constitute the core psychopathology in a subset of
schizophrenia. Commenting and discussing voices might be perceived under the
pressure of increased attention to environmental factors that relate to the patient's
social fears and wishes. Secondarily, delusions about the possession of thoughts
and disorders of self-experience may develop.
9. Behrendt, R. P. Underconstrained perception: a theoretical approach to the nature and
function of verbal hallucinations. Compr-Psychiatry. 1998 Jul; 39(4): 236-48;
ISSN: 0010-440X.
UNITED-STATES. We do not see the world as it is. Perception forms a
subjective image of the world in a language that has proven to be adaptive to our
interaction with the external world. Perception is mainly determined by current
needs of the organism and goals of behavior. Sensory processing itself does not
culminate in perception and is not essential for perception, since perception
derives from representations of internal symbols and their features. The current
stimulation of sensory organs does, however, constrain our perception.
Perception might be less constrained by the external world in cases of (1)
increased attention, (2) decreased sensory stimulation, or (3) facilitated formation
of cortical associations between representations of expectations and internal
symbols. Hallucinations are perceptions that are underconstrained by external
sensory stimulation. Verbal hallucinations that allow the patient to infer about his
self-image might constitute the core psychopathology in a subset of
schizophrenia. Commenting and discussing voices might be perceived under the
pressure of increased attention to environmental factors that relate to the patient's
social fears and wishes. Secondarily, delusions about the possession of thoughts
and disorders of self-experience may develop.
10. Belin, P.; McAdams, S.; Smith, B.; Savel, S.; Thivard, L.; Samson, S.; Samson, Y. The
functional anatomy of sound intensity discrimination. J-Neurosci. 1998 Aug 15;
18(16): 6388-94; ISSN: 0270-6474.
UNITED-STATES. The human neuroanatomical substrate of sound intensity
discrimination was investigated by combining psychoacoustics and functional
neuroimaging. Seven normal subjects were trained to detect deviant sounds
presented with a slightly higher intensity than a standard harmonic sound, using a
Go/No Go paradigm. Individual psychometric curves were carefully assessed
using a three-step psychoacoustic procedure. Subjects were scanned while
passively listening to the standard sound and while discriminating changes in
sound intensity at four different performance levels (d' = 1.5, 2.5, 3.5, and 4.5).
Analysis of regional cerebral blood flow data outlined activation, during the
discrimination conditions, of a right hemispheric frontoparietal network already
reported in other studies of selective or sustained attention to sensory input, and
in which activity appeared inversely proportional to intensity discriminability.
Conversely, a right posterior temporal region included in secondary auditory
cortex was activated during discrimination of sound intensity independently of
performance level. These findings suggest that discrimination of sound intensity
involves two different cortical networks: a supramodal right frontoparietal
network responsible for allocation of sensory attentional resources, and a region
of secondary auditory cortex specifically involved in sensory computation of
sound intensity differences.
11. Belin, P.; McAdams, S.; Smith, B.; Savel, S.; Thivard, L.; Samson, S.; Samson, Y. The
functional anatomy of sound intensity discrimination. J-Neurosci. 1998 Aug 15;
18(16): 6388-94; ISSN: 0270-6474.
UNITED-STATES. The human neuroanatomical substrate of sound intensity
discrimination was investigated by combining psychoacoustics and functional
neuroimaging. Seven normal subjects were trained to detect deviant sounds
presented with a slightly higher intensity than a standard harmonic sound, using a
Go/No Go paradigm. Individual psychometric curves were carefully assessed
using a three-step psychoacoustic procedure. Subjects were scanned while
passively listening to the standard sound and while discriminating changes in
sound intensity at four different performance levels (d' = 1.5, 2.5, 3.5, and 4.5).
Analysis of regional cerebral blood flow data outlined activation, during the
discrimination conditions, of a right hemispheric frontoparietal network already
reported in other studies of selective or sustained attention to sensory input, and
in which activity appeared inversely proportional to intensity discriminability.
Conversely, a right posterior temporal region included in secondary auditory
cortex was activated during discrimination of sound intensity independently of
performance level. These findings suggest that discrimination of sound intensity
involves two different cortical networks: a supramodal right frontoparietal
network responsible for allocation of sensory attentional resources, and a region
of secondary auditory cortex specifically involved in sensory computation of
sound intensity differences.
12. Bezard, E.; Bioulac, B.; Gross, C. E. Glutamatergic compensatory mechanisms in
experimental parkinsonism. Prog-Neuropsychopharmacol-Biol-Psychiatry. 1998
May; 22(4): 609-23; ISSN: 0278-5846.
ENGLAND. 1. Injection cannulae allowing access to the SNc were implanted
bilaterally in four monkeys. Once animals had recovered from the operation, daily
low-dose treatment with MPTP was started. 2. Group I comprised two monkeys
under treatment with MPTP, but still asymptomatic. Group II comprised two
monkeys treated with MPTP and presenting clinical symptoms. 3. Both groups
received daily intracranial injections of kynurenic acid in order to block the
glutamatergic afferents to the SNc. 4. In the first group of asymptomatic
monkeys, kynurenic acid induced parkinsonian motor abnormalities. In the second
group of symptomatic monkeys, it increased the severity of clinical signs. 5.
Glutamatergic inputs to the SNc would therefore appear to be implicated in
compensatory phenomena at different stages of experimental parkinsonism.. 0; 0;
28289-54-5; 492-27-3.
13. Blakemore, S. J.; Rees, G.; Frith, C. D. How do we predict the consequences of our
actions? A functional imaging study. Neuropsychologia. 1998 Jun; 36(6): 521-9;
ISSN: 0028-3932.
ENGLAND. Humans are readily able to distinguish expected and unexpected
sensory events. Whether a single mechanism underlies this ability is unknown.
The most common type of expected sensory events are those generated as a
consequence of self-generated actions. Using H2 15O PET, we studied brain
responses to such predictable sensory events (tones) and to similar unpredictable
events and especially how the processing of predictable sensory events is
modified by the context of a causative self-generated action. Increases in activity
when the tones were unpredictable were seen in the inferior and superior temporal
lobe bilaterally, the right parahippocampal gyrus and right parietal cortex. Self-
generated actions produced activity in a number of motor and premotor areas,
including dorsolateral prefrontal cortex. We observed an interaction between the
predictability of stimuli and self-generated actions in several areas, including the
medial posterior cingulate cortex, left insula, dorsomedial thalamus, superior
colliculus and right inferior temporal cortex. This modulation of activity
associated with stimulus predictability in the context of self-generated actions
implies that these areas may be involved in self-monitoring processes. Detection
of expected stimuli and the detection of the sensory consequences of self-
generated actions appear to be functionally distinct processes, and are carried out
in different cortical areas. These observations support theoretical approaches to
cognition that postulate the existence of a self-monitoring system.. 0; 7732-18-5.
14. Blakemore, S. J.; Rees, G.; Frith, C. D. How do we predict the consequences of our
actions? A functional imaging study. Neuropsychologia. 1998 Jun; 36(6): 521-9;
ISSN: 0028-3932.
ENGLAND. Humans are readily able to distinguish expected and unexpected
sensory events. Whether a single mechanism underlies this ability is unknown.
The most common type of expected sensory events are those generated as a
consequence of self-generated actions. Using H2 15O PET, we studied brain
responses to such predictable sensory events (tones) and to similar unpredictable
events and especially how the processing of predictable sensory events is
modified by the context of a causative self-generated action. Increases in activity
when the tones were unpredictable were seen in the inferior and superior temporal
lobe bilaterally, the right parahippocampal gyrus and right parietal cortex. Self-
generated actions produced activity in a number of motor and premotor areas,
including dorsolateral prefrontal cortex. We observed an interaction between the
predictability of stimuli and self-generated actions in several areas, including the
medial posterior cingulate cortex, left insula, dorsomedial thalamus, superior
colliculus and right inferior temporal cortex. This modulation of activity
associated with stimulus predictability in the context of self-generated actions
implies that these areas may be involved in self-monitoring processes. Detection
of expected stimuli and the detection of the sensory consequences of self-
generated actions appear to be functionally distinct processes, and are carried out
in different cortical areas. These observations support theoretical approaches to
cognition that postulate the existence of a self-monitoring system.. 0; 7732-18-5.
15. Bonci, A.; Grillner, P.; Mercuri, N. B.; Bernardi, G. L-Type calcium channels mediate
a slow excitatory synaptic transmission in rat midbrain dopaminergic neurons. J-
Neurosci. 1998 Sep 1; 18(17): 6693-703; ISSN: 0270-6474.
UNITED-STATES. Patch pipettes were used to record whole-cell synaptic
currents under voltage-clamp in dopaminergic neurons in slices of rat substantia
nigra pars compacta and ventral tegmental area. We report that dihydropyridines
(DHPs), L-type Ca2+ channel antagonists, depressed a slow EPSC (EPSCslow)
evoked by a train of focally delivered electrical stimuli. In fact, the amplitude of
the EPSCslow was reduced by the DHP antagonists nifedipine (1-100 microM),
nimodipine (1-100 microM), and isradipine (30 nM-100 microM) in a
concentration-dependent and reversible manner. On the other hand, Bay-K 8644
(1 microM), an L-type Ca2+ channel agonist, increased the EPSCslow. The DHPs
depressed the EPSCslow only when the high-frequency stimulation that was used
to evoke this synaptic current lasted >70 msec. On the other hand, Bay-K 8644
increased the amplitude of the EPSCslow only when it was evoked by a train <70
msec. Moreover, the DHPs did not affect the EPSCfast, the IPSCfast, and the
IPSCslow. The inhibition of the EPSCslow caused by the DHPs is attributed to
presynaptic mechanisms because (1) the inward current generated by exogenously
administered glutamate was not affected and (2) the EPSCslow was reduced to a
similar degree even when the activation state of postsynaptic L-type Ca2+
channels was changed by holding the neurons at -100, -60, and +30 mV. Finally, a
DHP-sensitive component of the EPSCslow could even be detected after the
blockade of N-, Q-, and P-type Ca2+ channels by the combination of omega-
conotoxin GVIA, omega-agatoxin IVA, and omega-conotoxin MVIIC. Taken
together, these results indicate that under certain patterns of synaptic activity, L-
type Ca2+ channels regulate the synaptic release of excitatory amino acids on the
dopaminergic neurons of the ventral mesencephalon.. 0; 0; 0; 51-61-6; 71145-03-
4.
16. Bosworth, C. F.; Sample, P. A.; Gupta, N.; Bathija, R.; Weinreb, R. N. Motion
automated perimetry identifies early glaucomatous field defects. Arch-
Ophthalmol. 1998 Sep; 116(9): 1153-8; ISSN: 0003-9950.
UNITED-STATES. OBJECTIVE: To determine if motion automated perimetry
can identify early glaucomatous visual field defects in patients with suspected
glaucoma (by disc), those with ocular hypertension, and those with primary
open-angle glaucoma. METHODS: Motion automated perimetry, a foveally
centered motion test, and standard visual field tests were conducted on one
randomly selected eye of normal patients (n = 38), patients with suspected
glaucoma (by disc) (n = 28), patients with ocular hypertension (n = 18), and
patients with primary open-angle glaucoma (n = 21). Subjects' performance on
both motion tests were compared with their performance on standard perimetry.
RESULTS: Perimetric motion thresholds significantly distinguished the groups
(P< or =.001), while the foveally centered motion test was unable to separate
them (P< or =.32). Of the total patients, 90.5% of those with glaucoma, 39.3% of
those with suspected glaucoma, 27.8% of those with ocular hypertension, and
5.3% of the normal subjects had abnormal results on motion automated perimetry
testing. Perimetric motion thresholds were significantly correlated with standard
visual field thresholds (P< or =.001). CONCLUSION: Motion automated
perimetry identifies visual field defects in patients who already show standard
visual field loss as well as in a moderate percentage of those with suspected
glaucoma and ocular hypertension, indicating that the testing of discrete locations
might be necessary for increased diagnostic utility.
17. Bosworth, C. F.; Sample, P. A.; Gupta, N.; Bathija, R.; Weinreb, R. N. Motion
automated perimetry identifies early glaucomatous field defects. Arch-
Ophthalmol. 1998 Sep; 116(9): 1153-8; ISSN: 0003-9950.
UNITED-STATES. OBJECTIVE: To determine if motion automated perimetry
can identify early glaucomatous visual field defects in patients with suspected
glaucoma (by disc), those with ocular hypertension, and those with primary
open-angle glaucoma. METHODS: Motion automated perimetry, a foveally
centered motion test, and standard visual field tests were conducted on one
randomly selected eye of normal patients (n = 38), patients with suspected
glaucoma (by disc) (n = 28), patients with ocular hypertension (n = 18), and
patients with primary open-angle glaucoma (n = 21). Subjects' performance on
both motion tests were compared with their performance on standard perimetry.
RESULTS: Perimetric motion thresholds significantly distinguished the groups
(P< or =.001), while the foveally centered motion test was unable to separate
them (P< or =.32). Of the total patients, 90.5% of those with glaucoma, 39.3% of
those with suspected glaucoma, 27.8% of those with ocular hypertension, and
5.3% of the normal subjects had abnormal results on motion automated perimetry
testing. Perimetric motion thresholds were significantly correlated with standard
visual field thresholds (P< or =.001). CONCLUSION: Motion automated
perimetry identifies visual field defects in patients who already show standard
visual field loss as well as in a moderate percentage of those with suspected
glaucoma and ocular hypertension, indicating that the testing of discrete locations
might be necessary for increased diagnostic utility.
18. Bowyer, J. F.; Frame, L. T.; Clausing, P.; Nagamoto Combs, K.; Osterhout, C. A.;
Sterling, C. R.; Tank, A. W. Long-term effects of amphetamine neurotoxicity on
tyrosine hydroxylase mRNA and protein in aged rats. J-Pharmacol-Exp-Ther.
1998 Aug; 286(2): 1074-85; ISSN: 0022-3565.
UNITED-STATES. Four injections (intraperitoneal) of 3 mg/kg amphetamine (2
hr apart) produced pronounced hyperthermia and sustained decreases in
dopamine levels and tyrosine hydroxylase (TH) protein levels in the striatum of
15-month-old male rats. A partial recovery of striatal dopamine levels was
observed at 4 months after amphetamine. In contrast, TH mRNA and TH protein
levels in the midbrain were unaffected at all time points tested up to 4 months
after amphetamine treatment. The number of TH-immunopositive cells in the
midbrain was also unchanged at 4 months after amphetamine, even though the
number of TH-positive axons in the striatum remained dramatically decreased at
this time point. Interestingly, TH-immunopositive cell bodies were observed 4
months after amphetamine in the lateral caudate/putamen, defined anteriorly by
the genu of the corpus collosum and posteriorly by the junction of the anterior
commissures; these striatal TH-positive cells were not observed in saline- or
amphetamine-treated rats that did not become hyperthermic. In addition, low
levels (orders of magnitude lower than that present in the midbrain) of TH mRNA
were detected using reverse transcription-polymerase chain reaction in the
striatum of these amphetamine-treated rats. Our results suggest that even though
there is a partial recovery of striatal dopamine levels, which occurs within 4
months after amphetamine treatment, this recovery is not associated with
increased TH gene expression in the midbrain. Furthermore, new TH-positive
cells are generated in the striatum at this 4-month time point.. EC 1.14.16.2; EC
1.2.1.9; 0; 0; 300-62-9; 51-61-6.
19. Brandt, T.; Bartenstein, P.; Janek, A.; Dieterich, M. Reciprocal inhibitory visual-
vestibular interaction. Visual motion stimulation deactivates the parieto-insular
vestibular cortex. Brain. 1998 Sep; 121( Pt 9): 1749-58; ISSN: 0006-8950.
ENGLAND. The vestibular system--a sensor of head accelerations--cannot
detect self-motion at constant velocity and thus requires supplementary visual
information. The perception of self-motion during constant velocity movement is
completely dependent on visually induced vection. This can be linear vection or
circular vection (CV). CV is induced by large-field visual motion stimulation
during which the stationary subject perceives the moving surroundings as being
stable and himself as being moved. To determine the unknown cortical visual-
vestibular interaction during CV, we conducted a PET activation study on CV in
10 human volunteers. The PET images of cortical areas activated during visual
motion stimulation without CV were compared with those with CV. Hitherto, CV
was explained neurophysiologically by visual-vestibular convergence with
activation of the vestibular nuclei, thalamic subnuclei and vestibular cortex. If CV
were mediated by the vestibular cortex, one would expect that an adequate visual
motion stimulus would activate both the visual and vestibular cortex. Contrary to
this expectation, it was shown for the first time that visual motion stimulation
with CV not only activates a medial parieto-occipital visual area bilaterally,
separate from middle temporal/medial superior temporal areas, it also
simultaneously deactivates the parieto-insular vestibular cortex. There was a
positive correlation between the perceived intensity of CV and relative changes in
regional CBF in parietal and occipital areas. These findings support a new
functional interpretation: reciprocal inhibitory visual-vestibular interaction as a
multisensory mechanism for self-motion perception. Inhibitory visual-vestibular
interaction might protect visual perception of self-motion from potential
vestibular mismatches caused by involuntary head accelerations during
locomotion, and this would allow the dominant sensorial weight during self-
motion perception to shift from one sensory modality to the other.
20. Brandt, T.; Bartenstein, P.; Janek, A.; Dieterich, M. Reciprocal inhibitory visual-
vestibular interaction. Visual motion stimulation deactivates the parieto-insular
vestibular cortex. Brain. 1998 Sep; 121( Pt 9): 1749-58; ISSN: 0006-8950.
ENGLAND. The vestibular system--a sensor of head accelerations--cannot
detect self-motion at constant velocity and thus requires supplementary visual
information. The perception of self-motion during constant velocity movement is
completely dependent on visually induced vection. This can be linear vection or
circular vection (CV). CV is induced by large-field visual motion stimulation
during which the stationary subject perceives the moving surroundings as being
stable and himself as being moved. To determine the unknown cortical visual-
vestibular interaction during CV, we conducted a PET activation study on CV in
10 human volunteers. The PET images of cortical areas activated during visual
motion stimulation without CV were compared with those with CV. Hitherto, CV
was explained neurophysiologically by visual-vestibular convergence with
activation of the vestibular nuclei, thalamic subnuclei and vestibular cortex. If CV
were mediated by the vestibular cortex, one would expect that an adequate visual
motion stimulus would activate both the visual and vestibular cortex. Contrary to
this expectation, it was shown for the first time that visual motion stimulation
with CV not only activates a medial parieto-occipital visual area bilaterally,
separate from middle temporal/medial superior temporal areas, it also
simultaneously deactivates the parieto-insular vestibular cortex. There was a
positive correlation between the perceived intensity of CV and relative changes in
regional CBF in parietal and occipital areas. These findings support a new
functional interpretation: reciprocal inhibitory visual-vestibular interaction as a
multisensory mechanism for self-motion perception. Inhibitory visual-vestibular
interaction might protect visual perception of self-motion from potential
vestibular mismatches caused by involuntary head accelerations during
locomotion, and this would allow the dominant sensorial weight during self-
motion perception to shift from one sensory modality to the other.
21. Britten, K. H. Clustering of response selectivity in the medial superior temporal area
of extrastriate cortex in the macaque monkey. Vis-Neurosci. 1998 May; 15(3):
553-8; ISSN: 0952-5238.
ENGLAND. Ever since being described by Mountcastle (Mountcastle, 1957),
columnar organization of sensory cortical areas has provided key leverage into
understanding the functional organization of neocortex. Columnar or clustered
organization of neurons sharing like properties is now known to be widespread,
and probably universal in primary sensory areas. Visual cortex in primates
consists of a primary area and a large number of secondary areas, which are
organized in a manner both hierarchical and parallel (Felleman & Van Essen, 1991;
Young, 1993; Young et al., 1995). One major component in the organization of
extrastriate visual cortex appears to be the division into dorsal and ventral
"streams" of processing (Ungerleider & Mishkin, 1982), each of which is
organized hierarchically. Within each, columnar organization exists at early stages,
but becomes less clear at higher levels. Columnar organization has been described
at the highest level of the ventral stream, inferotemporal cortex (IT, Saleem et al.,
1993; Fujita & Fujita, 1996; Tanaka, 1996), but has not been well characterized at
the higher levels of the dorsal stream. Hints of such organization are found in the
literature (Saito et al., 1986; Lagae et al., 1994), but systematic measurements are
needed. In this paper, I report the existence of clustered organization in the medial
superior temporal area (MST) of the dorsal stream, which is arguably the highest
dominantly visual area on this pathway. I have measured the selectivity of both
single- and multiple-unit activity along oblique electrode penetrations through this
area to three different kinds of optic flow stimuli, and find that nearby neurons are
more similar in their tuning than are more distant ones. This observation
documents the existence of some form of clustered organization and supports the
importance of this area in the processing of optic flow information.
22. Britten, K. H. Clustering of response selectivity in the medial superior temporal area
of extrastriate cortex in the macaque monkey. Vis-Neurosci. 1998 May; 15(3):
553-8; ISSN: 0952-5238.
ENGLAND. Ever since being described by Mountcastle (Mountcastle, 1957),
columnar organization of sensory cortical areas has provided key leverage into
understanding the functional organization of neocortex. Columnar or clustered
organization of neurons sharing like properties is now known to be widespread,
and probably universal in primary sensory areas. Visual cortex in primates
consists of a primary area and a large number of secondary areas, which are
organized in a manner both hierarchical and parallel (Felleman & Van Essen, 1991;
Young, 1993; Young et al., 1995). One major component in the organization of
extrastriate visual cortex appears to be the division into dorsal and ventral
"streams" of processing (Ungerleider & Mishkin, 1982), each of which is
organized hierarchically. Within each, columnar organization exists at early stages,
but becomes less clear at higher levels. Columnar organization has been described
at the highest level of the ventral stream, inferotemporal cortex (IT, Saleem et al.,
1993; Fujita & Fujita, 1996; Tanaka, 1996), but has not been well characterized at
the higher levels of the dorsal stream. Hints of such organization are found in the
literature (Saito et al., 1986; Lagae et al., 1994), but systematic measurements are
needed. In this paper, I report the existence of clustered organization in the medial
superior temporal area (MST) of the dorsal stream, which is arguably the highest
dominantly visual area on this pathway. I have measured the selectivity of both
single- and multiple-unit activity along oblique electrode penetrations through this
area to three different kinds of optic flow stimuli, and find that nearby neurons are
more similar in their tuning than are more distant ones. This observation
documents the existence of some form of clustered organization and supports the
importance of this area in the processing of optic flow information.
23. Britten, K. H.; Newsome, W. T. Tuning bandwidths for near-threshold stimuli in area
MT. J-Neurophysiol. 1998 Aug; 80(2): 762-70; ISSN: 0022-3077.
UNITED-STATES. It is not known whether psychophysical performance
depends primarily on small numbers of neurons optimally tuned to specific visual
stimuli, or on larger populations of neurons that vary widely in their properties.
Tuning bandwidths of single cells can provide important insight into this issue,
yet most bandwidth measurements have been made using suprathreshold visual
stimuli, whereas psychophysical measurements are frequently obtained near
threshold. We therefore examined the directional tuning of cells in the middle
temporal area (MT, or V5) using perithreshold, stochastic motion stimuli that we
have employed extensively in combined psychophysical and physiological
studies. The strength of the motion signal (coherence) in these displays can be
varied independently of its direction. For each MT neuron, we characterized the
directional bandwidth by fitting Gaussian functions to directional tuning data
obtained at each of several motion coherences. Directional bandwidth increased
modestly as the coherence of the stimulus was reduced. We then assessed the
ability of MT neurons to discriminate opposed directions of motion along six
equally spaced axes of motion spanning 180 degrees. A signal detection analysis
yielded neurometric functions for each axis of motion, from which neural
thresholds could be extracted. Neural thresholds remained surprisingly low as the
axis of motion diverged from the neuron's preferred-null axis, forming a plateau of
high to medium sensitivity that extended approximately 45 degrees on either side
of the preferred-null axis. We conclude that directional tuning remains broad in
MT when motion signals are reduced to near-threshold values. Thus directional
information is widely distributed in MT, even near the limits of psychophysical
performance. These observations support models in which relatively large
numbers of signals are pooled to inform psychophysical decisions.
24. Britten, K. H.; Newsome, W. T. Tuning bandwidths for near-threshold stimuli in area
MT. J-Neurophysiol. 1998 Aug; 80(2): 762-70; ISSN: 0022-3077.
UNITED-STATES. It is not known whether psychophysical performance
depends primarily on small numbers of neurons optimally tuned to specific visual
stimuli, or on larger populations of neurons that vary widely in their properties.
Tuning bandwidths of single cells can provide important insight into this issue,
yet most bandwidth measurements have been made using suprathreshold visual
stimuli, whereas psychophysical measurements are frequently obtained near
threshold. We therefore examined the directional tuning of cells in the middle
temporal area (MT, or V5) using perithreshold, stochastic motion stimuli that we
have employed extensively in combined psychophysical and physiological
studies. The strength of the motion signal (coherence) in these displays can be
varied independently of its direction. For each MT neuron, we characterized the
directional bandwidth by fitting Gaussian functions to directional tuning data
obtained at each of several motion coherences. Directional bandwidth increased
modestly as the coherence of the stimulus was reduced. We then assessed the
ability of MT neurons to discriminate opposed directions of motion along six
equally spaced axes of motion spanning 180 degrees. A signal detection analysis
yielded neurometric functions for each axis of motion, from which neural
thresholds could be extracted. Neural thresholds remained surprisingly low as the
axis of motion diverged from the neuron's preferred-null axis, forming a plateau of
high to medium sensitivity that extended approximately 45 degrees on either side
of the preferred-null axis. We conclude that directional tuning remains broad in
MT when motion signals are reduced to near-threshold values. Thus directional
information is widely distributed in MT, even near the limits of psychophysical
performance. These observations support models in which relatively large
numbers of signals are pooled to inform psychophysical decisions.
25. Burke, R. E.; Kholodilov, N. G. Programmed cell death: does it play a role in
Parkinson's disease? Ann-Neurol. 1998 Sep; 44(3 Suppl 1): S126-33; ISSN: 0364-
5134.
UNITED-STATES. In recent years, the possibility that programmed cell death
(PCD), which is mediated by genetic programs intrinsic to the cell, may underlie
the degeneration of neurons that occurs in Parkinson's disease (PD) and allied
disorders has become an important hypothesis. Although PCD was originally
identified in tissues as a normal developmental phenomenon, there is no question
that it can also occur in neurologic disease and models thereof. The possibility
that PCD could occur in dopamine neurons in degenerative disease is made
plausible by the observations that natural cell death, with the morphology of
apoptosis, does occur in these neurons and that this event is regulated by
developmental target interactions. In addition, it has been shown that apoptotic
death can be induced in these neurons in some animal models of parkinsonism. We
have shown, for example, that apoptosis can be induced during development by
intrastriatal injection of the neurotoxin 6-hydroxydopamine. Other investigators
have shown that apoptosis can be induced in a chronic model of 1-methyl-4-
phenyl-1,2,3,6-tetrahydropyride toxicity. However, investigations in human PD
brains have yielded mixed results thus far, with some investigators identifying
evidence of apoptotic death but others not. Further investigation of human
postmortem tissue will benefit from a more complete understanding of the
molecular basis of PCD in dopamine neurons, such that its molecular features can
be investigated, rather than strictly relying on the morphologic markers presently
available.. 51-61-6.
26. Carpenter, M. G.; Bellos, A.; Patla, A. E. Is backward stepping over obstacles
achieved through a simple temporal reversal of forward stepping? Int-J-Neurosci.
1998 Apr; 93(3-4): 189-96; ISSN: 0020-7454.
ENGLAND. The main purpose of the study was to examine whether backward
stepping over obstacles was a simple temporal reversal of kinematic and muscle
activation patterns found in forward obstacle avoidance. Obstacle avoidance was
used as a probe to represent one aspect of walking over variable terrain.
Kinematics, trajectories and muscle activation profiles for forward versus
backward stepping over obstacles revealed that the simple reversal of locomotor
patterns observed for level walking cannot be applied to obstacle avoidance.
However, key kinematic data and limb trajectories for backward leading limb
stepping were found to be similar to existing forward trailing limb data. Therefore,
it appears that stepping over obstacles requires a complex upper level
reorganization of the basic locomotor pattern based on biomechanical and sensory
feedback.
27. Carpenter, M. G.; Bellos, A.; Patla, A. E. Is backward stepping over obstacles
achieved through a simple temporal reversal of forward stepping? Int-J-Neurosci.
1998 Apr; 93(3-4): 189-96; ISSN: 0020-7454.
ENGLAND. The main purpose of the study was to examine whether backward
stepping over obstacles was a simple temporal reversal of kinematic and muscle
activation patterns found in forward obstacle avoidance. Obstacle avoidance was
used as a probe to represent one aspect of walking over variable terrain.
Kinematics, trajectories and muscle activation profiles for forward versus
backward stepping over obstacles revealed that the simple reversal of locomotor
patterns observed for level walking cannot be applied to obstacle avoidance.
However, key kinematic data and limb trajectories for backward leading limb
stepping were found to be similar to existing forward trailing limb data. Therefore,
it appears that stepping over obstacles requires a complex upper level
reorganization of the basic locomotor pattern based on biomechanical and sensory
feedback.
28. Cases, O.; Lebrand, C.; Giros, B.; Vitalis, T.; De Maeyer, E.; Caron, M. G.; Price, D.
J.; Gaspar, P.; Seif, I. Plasma membrane transporters of serotonin, dopamine, and
norepinephrine mediate serotonin accumulation in atypical locations in the
developing brain of monoamine oxidase A knock-outs. J-Neurosci. 1998 Sep 1;
18(17): 6914-27; ISSN: 0270-6474.
UNITED-STATES. Genetic loss or pharmacological inhibition of monoamine
oxidase A (MAOA) in mice leads to a large increase in whole-brain levels of
serotonin (5-HT). Excess 5-HT in mouse neonates prevents the normal barrel-like
clustering of thalamic axons in the somatosensory cortex. Projection fields of other
neuron populations may develop abnormally. In the present study, we have
analyzed the localization of 5-HT immunolabeling in the developing brain of
MAOA knock-out mice. We show numerous atypical locations of 5-HT during
embryonic and postnatal development. Catecholaminergic cells of the substantia
nigra, ventral tegmental area, hypothalamus, and locus ceruleus display transient
5-HT immunoreactivity. Pharmacological treatments inhibiting specific
monoamine plasma membrane transporters and genetic crosses with mice lacking
the dopamine plasma membrane transporter show that the accumulation of 5-HT
in these catecholaminergic cells is attributable to 5-HT uptake via the dopamine or
the norepinephrine plasma membrane transporter. In the telencephalon, transient
5-HT immunolabeling is observed in neurons in the CA1 and CA3 fields of the
hippocampus, the central amygdala, the indusium griseum, and the deep layers of
the anterior cingulate and retrosplenial cortices. In the diencephalon, primary
sensory nuclei, as well as the mediodorsal, centrolateral, oval paracentral,
submedial, posterior, and lateral posterior thalamic nuclei, are transiently 5-HT
immunolabeled. The cortical projections of these thalamic nuclei are also labeled.
In the brainstem, neurons in the lateral superior olivary nucleus and the
anteroventral cochlear nucleus are transiently 5-HT immunolabeled. None of these
structures appear to express the monoamine biosynthetic enzyme L-aromatic
amino acid decarboxylase. The administration of monoamine plasma membrane
transporter inhibitors indicates that the 5-HT immunolabeling in these structures
is attributable to an uptake of 5-HT by the 5-HT plasma membrane transporter.
This points to neuron populations that form highly precise projection maps that
could be affected by 5-HT during specific developmental stages.. EC 1.4.3.4; 0; 0;
0; 0; 0; 136253-20-8; 50-67-9; 51-41-2; 51-61-6.
29. Chan, P. K.; Leung, C. K.; Yung, W. H. Differential expression of pre- and
postsynaptic GABA(B) receptors in rat substantia nigra pars reticulata neurones.
Eur-J-Pharmacol. 1998 May 22; 349(2-3): 187-97; ISSN: 0014-2999.
NETHERLANDS. Whole-cell recordings were made from substantia nigra pars
reticulata in rat midbrain slices to study the functional expression of pre- and
postsynaptic GABA(B) receptors in GABA output neurones. Baclofen (up to
300 microM) dose-dependently activated a weak current which was insensitive to
tetrodotoxin and Ca2+-free solution but blocked by Ba2+ and 2-OH-saclofen. The
maximum current activated by baclofen (30 microM) was 43.0 +/- 4.5 pA (n =
27), representing only 23% of that in dopamine neurones. Baclofen (1-30
microM) also reduced the frequency of the GABA(A) receptor-mediated
miniature inhibitory postsynaptic currents while the distribution of their
amplitudes was unaffected. This presynaptic effect of baclofen, prominent at a
concentration as low as 1 microM, was sensitive to 2-OH-saclofen and occluded
by Cd2+, but was unaffected by Ba2+. The results suggest a predominant role of
the presynaptic GABA(B) receptors in substantia nigra pars reticulata. The
relative abundance of pre- and postsynaptic GABA(B) receptor subtypes in this
brain region may also be important in mediating the anticonvulsant effect of
baclofen in rats.. 0; 0; 0; 1134-47-0.
30. Charvet, I.; Hemming, F. J.; Feuerstein, C.; Saxod, R. Mosaic distribution of
chondroitin and keratan sulphate in the developing rat striatum: possible
involvement of proteoglycans in the organization of the nigrostriatal system.
Brain-Res-Dev-Brain-Res. 1998 Aug 8; 109(2): 229-44; ISSN: 0165-3806.
NETHERLANDS. The striatum of the mammalian basal ganglia is composed of
two neurochemically distinct compartments termed patches and matrix that
contribute overall to a mosaic organization. Glycosaminoglycans (GAGs), the
sugar moieties of proteoglycans, provide specific spatio-temporal guidance cues
during the development of several functional neural systems. However, their
distribution within the nigrostriatal system has not been investigated yet. Here,
the immunohistochemical distributions of unsulphated (C0S), 4-sulphated (C4S)
and 6-sulphated chondroitin (C6S) and keratan sulphate (KS) were examined in
the developing neostriatum of rat and compared with the distribution of
dopaminergic terminals. All the chondroitin sulphate (CS) isomers are
homogeneously expressed in the embryonic striatum. After birth, C0S and C6S
reveal the striatal mosaic in being preferentially expressed within the matrix
compartment and in boundaries around patches whereas the C4S epitope is
present in both compartments, with a slight patchy distribution. KS expression is
detected first in the patches during the early postnatal period and subsequently
only in the matrix compartment. All these GAG expressions disappear as the
brain matures except for C4S which remains high throughout adult life.
Furthermore, studies within the developing medial forebrain bundle reveal that CS
isomers, but not KS, are expressed in and around the dopamine axonal tract but
show similar developmental patterns of distribution which do not appear to be
specifically associated with the nigrostriatal pathway. These results suggest a
possible implication of proteoglycans during the development of the striatum and
may be useful for understanding the complex cellular and molecular interactions in
degeneration and plasticity of the nigrostriatal circuit in Parkinson's disease.
Copyright 1998 Elsevier Science B.V.. 0; 0; 0; 9007-27-6; 9056-36-4.
31. Cropper, S. J. Detection of chromatic and luminance contrast modulation by the
visual system. J-Opt-Soc-Am-A-Opt-Image-Sci-Vis. 1998 Aug; 15(8): 1969-86;
ISSN: 1084-7529.
UNITED-STATES. The data presented in this paper examine the ability of
observers to detect a modulation in the contrast of chromatic and luminance
gratings as a function of the carrier contrast, duration, and spatial frequency. The
nature of the signal underlying this ability is investigated by examining both the
paradigm used to make the measurement and the effect of grating masks on
performance in the tasks. The results show that observers' ability to discriminate
amplitude modulation from an unmodulated carrier is dependent on carrier
contrast but only up to approximately 5-8 times carrier-detection threshold.
Discrimination is, however, independent of spatial frequency [10-1 cycles per
degree (cpd) component-frequency range], carrier color, and, most surprisingly,
stimulus duration (1000-30 ms). This set of experiments compliments data from
previous papers and assimilates many of the conclusions drawn from this
previous data. There is absolutely no evidence for the existence of a distortion
product mediating performance under any of the current conditions, and the data
seriously question whether the visual system might use such a signal even if it
does exist under more extreme conditions than those used here. The evidence
suggests that the visual system detects variations in both chromatic and luminance
contrast by means of a mechanism operating locally upon the spatial structure of
the carrier.
32. Cropper, S. J. Detection of chromatic and luminance contrast modulation by the
visual system. J-Opt-Soc-Am-A-Opt-Image-Sci-Vis. 1998 Aug; 15(8): 1969-86;
ISSN: 1084-7529.
UNITED-STATES. The data presented in this paper examine the ability of
observers to detect a modulation in the contrast of chromatic and luminance
gratings as a function of the carrier contrast, duration, and spatial frequency. The
nature of the signal underlying this ability is investigated by examining both the
paradigm used to make the measurement and the effect of grating masks on
performance in the tasks. The results show that observers' ability to discriminate
amplitude modulation from an unmodulated carrier is dependent on carrier
contrast but only up to approximately 5-8 times carrier-detection threshold.
Discrimination is, however, independent of spatial frequency [10-1 cycles per
degree (cpd) component-frequency range], carrier color, and, most surprisingly,
stimulus duration (1000-30 ms). This set of experiments compliments data from
previous papers and assimilates many of the conclusions drawn from this
previous data. There is absolutely no evidence for the existence of a distortion
product mediating performance under any of the current conditions, and the data
seriously question whether the visual system might use such a signal even if it
does exist under more extreme conditions than those used here. The evidence
suggests that the visual system detects variations in both chromatic and luminance
contrast by means of a mechanism operating locally upon the spatial structure of
the carrier.
33. Dai, M.; Tepper, J. M. Do silent dopaminergic neurons exist in rat substantia nigra in
vivo? Neuroscience. 1998 Aug; 85(4): 1089-99; ISSN: 0306-4522.
UNITED-STATES. A subpopulation of inactive or "silent" dopaminergic
neurons has been reported to exist in vivo in rat substantia nigra, comprising up to
50% of nigral dopaminergic neurons. The existence of this large proportion of
silent neurons has been inferred from various experimental manipulations, but
never demonstrated directly. In the present study, striatal or medial forebrain
bundle stimulation was used to activate antidromically substantia nigra
dopaminergic neurons in vivo. Antidromic spikes of dopaminergic neurons
observed by extracellular single-unit recordings in the absence of spontaneous
activity were employed as indicators of the presence of a silent cell. A total of
312 dopamine neurons were recorded, including 190 neurons that could be
antidromically activated from the striatum and/or the medial forebrain bundle. All
neurons exhibited spontaneous activity. The firing rates were unimodally
distributed about the mean of 4 spikes/s, and very few cells were observed to fire
at less than 0.5 spikes/s. The numbers of spontaneously active and antidromically
activated dopaminergic neurons per track were recorded and compared with the
number of antidromically responding silent dopaminergic neurons per track after
systemic apomorphine administration. Under control conditions, 0.80 +/- 0.10 or
1.36 +/- 0.13 spontaneously active neurons per track could be antidromically
activated at 1.0 mA by striatal or medial forebrain bundle stimulation,
respectively. After apomorphine completely suppressed spontaneous activity,
0.69 +/- 0.08 and 1.39 +/- 0.14 antidromic neurons per track were detected by
stimulating the striatum or medial forebrain bundle respectively at 1.0 mA,
demonstrating that silent dopaminergic neurons can be reliably identified through
antidromic activation. In sharp contrast to previous reports, these data suggest
that silent neurons do not comprise a substantial proportion of the total number
of dopaminergic neurons in the substantia nigra. Reverse chi2 analysis revealed
that, if they exist at all, silent dopaminergic neurons make up less than 2% of the
dopaminergic cells in the substantia nigra. These findings are related to current
theories of the mechanisms of action of antipsychotic drugs and the maintenance
of near-normal levels of dopamine in the striatum following large-scale loss of
nigral dopaminergic neurons.. 0; 51-61-6; 58-00-4.
34. Date, I.; Aoi, M.; Tomita, S.; Collins, F.; Ohmoto, T. GDNF administration induces
recovery of the nigrostriatal dopaminergic system both in young and aged
parkinsonian mice. Neuroreport. 1998 Jul 13; 9(10): 2365-9; ISSN: 0959-4965.
ENGLAND. Glial cell line-derived neurotrophic factor (GDNF) is a member of
the transforming growth factor beta superfamily and acts as a neurotrophic factor
for the nigrostriatal dopaminergic system. GDNF was injected stereotaxically into
the striatum of young (2 months old) and aged (12 months old) C57BL/6 mice
that were treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) 1
week earlier. Immunocytochemical and neurochemical analyses showed significant
recovery of the nigrostriatal dopaminergic system both in young and in aged mice.
Since Parkinson's disease is a neurodegenerative disorder mainly affecting elderly
people, this result demonstrates the potential usefulness of GDNF in treating
Parkinson's disease.. EC 1.14.16.2; 0; 0; 0; 0; 28289-54-5; 51-61-6.
35. David, V.; Durkin, T. P.; Cazala, P. Rewarding effects elicited by the microinjection
of either AMPA or NMDA glutamatergic antagonists into the ventral tegmental
area revealed by an intracranial self-administration paradigm in mice. Eur-J-
Neurosci. 1998 Apr; 10(4): 1394-402; ISSN: 0953-816X.
FRANCE. In order to study the functional role of the trans-synaptic neuronal
interaction between glutamatergic afferents and mesolimbic dopaminergic neurons
in internal reward processes, BALB/c male mice were unilaterally implanted with
a guide-cannula, the tip of which was positioned 1.5 mm above the ventral
tegmental area (VTA). On each day of the following experimental period, a
stainless steel injection cannula was inserted into the VTA in order to study the
eventual self-administration behaviour of either the competitive N-methyl-D-
aspartate antagonist, D(-)-2-amino-7-phosphonoheptanoic acid (AP-7) or the
alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid antagonist, 6,7-
dinitroquinoxaline-2,3-dione (DNQX) (3 ng/50 nL) using a spatial discrimination
task in a Y maze. Mice rapidly discriminated between the arm enabling a
microinjection of either of these glutamatergic antagonists and the neutral arm of
the maze, and a robust self-administration of either of these compounds was
observed from the first session of acquisition. These data provide strong evidence
that the intra-VTA microinjection of either of these subclasses of glutamatergic
antagonist produces an effect which is interpreted centrally by the experimental
subjects as being highly rewarding. Once the self-administration response had
been fully acquired by the experimental subjects, preinjection of the dopaminergic
D2 antagonist, sulpiride (50 mg/kg i.p.), 30 min before the test, produced a rapid
extinction of the self-administration response. This latter result demonstrates the
dopaminergic D2 receptor dependence of this intra-VTA self-administration of
both of these subclasses of glutamatergic antagonist. We conclude that the
different glutamatergic afferent neuronal inputs to the VTA globally exert, in vivo,
via the mediation of interposed endogenous GABAergic interneurons, a tonic
trans-synaptic inhibitory regulation of neuronal activity in the mesolimbic
dopaminergic pathway and that this complex neuronal interaction in the VTA
plays a significant functional part in the modulation of internal reward processes..
0; 0; 0; 0; 0; 15676-16-1; 2379-57-9; 76726-92-6; 85797-13-3.
36. Demb, J. B.; Boynton, G. M.; Best, M.; Heeger, D. J. Psychophysical evidence for a
magnocellular pathway deficit in dyslexia. Vision-Res. 1998 Jun; 38(11): 1555-9;
ISSN: 0042-6989.
ENGLAND. The relationship between reading ability and psychophysical
performance was examined to test the hypothesis that dyslexia is associated with
a deficit in the magnocellular (M) pathway. Speed discrimination thresholds and
contrast detection thresholds were measured under conditions (low mean
luminance, low spatial frequency, high temporal frequency) for which
psychophysical performance presumably depends on M pathway integrity.
Dyslexic subjects had higher psychophysical thresholds than controls in both the
speed discrimination and contrast detection tasks, but only the differences in
speed thresholds were statistically significant. In addition, there was a strong
correlation between individual differences in speed thresholds and reading rates.
These results support the hypothesis for an M pathway abnormality in dyslexia,
and suggest that motion discrimination may be a more sensitive psychophysical
predictor of dyslexia than contrast sensitivity.
37. Demb, J. B.; Boynton, G. M.; Best, M.; Heeger, D. J. Psychophysical evidence for a
magnocellular pathway deficit in dyslexia. Vision-Res. 1998 Jun; 38(11): 1555-9;
ISSN: 0042-6989.
ENGLAND. The relationship between reading ability and psychophysical
performance was examined to test the hypothesis that dyslexia is associated with
a deficit in the magnocellular (M) pathway. Speed discrimination thresholds and
contrast detection thresholds were measured under conditions (low mean
luminance, low spatial frequency, high temporal frequency) for which
psychophysical performance presumably depends on M pathway integrity.
Dyslexic subjects had higher psychophysical thresholds than controls in both the
speed discrimination and contrast detection tasks, but only the differences in
speed thresholds were statistically significant. In addition, there was a strong
correlation between individual differences in speed thresholds and reading rates.
These results support the hypothesis for an M pathway abnormality in dyslexia,
and suggest that motion discrimination may be a more sensitive psychophysical
predictor of dyslexia than contrast sensitivity.
38. Diana, M.; Melis, M.; Muntoni, A. L.; Gessa, G. L. Mesolimbic dopaminergic decline
after cannabinoid withdrawal. Proc-Natl-Acad-Sci-U-S-A. 1998 Aug 18; 95(17):
10269-73; ISSN: 0027-8424.
UNITED-STATES. The mesolimbic dopamine system has recently been
implicated in the long-term aversive consequences of withdrawal from major drugs
of abuse. In the present study we sought to determine whether mesolimbic
dopamine neurons are involved in the neurobiologic mechanisms underlying
withdrawal from chronic cannabinoid exposure. Rats were treated chronically with
the major psychoactive ingredient of hashish and marijuana, Delta9-
tetrahydrocannabinol (Delta9-THC). Administration of the cannabinoid
antagonist SR 141716A precipitated an intense behavioral withdrawal syndrome,
whereas abrupt Delta9-THC suspension failed to produce overt signs of
abstinence. In contrast, both groups showed a reduction in dopamine cells activity
as indicated by extracellular single unit recordings from antidromically identified
meso-accumbens dopamine neurons. The administration of Delta9-THC to
spontaneously withdrawn rats restored neuronal activity. Conversely, SR
141716A produced a further decrease of spontaneous activity in cannabinoid-
treated although it was ineffective in control rats. These data indicate that
withdrawal from chronic cannabinoid administration is associated with reduced
dopaminergic transmission in the limbic system, similar to that observed with
other addictive drugs; these changes in neuronal plasticity may play a role in drug
craving and relapse into drug addiction.. 1972-08-3; 51-61-6.
39. Drevets, W. C.; Ongur, D.; Price, J. L. Neuroimaging abnormalities in the subgenual
prefrontal cortex: implications for the pathophysiology of familial mood
disorders. Mol-Psychiatry. 1998 May; 3(3): 220-6, 190-1; ISSN: 1359-4184.
ENGLAND. The prefrontal cortex (PFC) ventral to the genu of the corpus
callosum has been implicated in the modulation of visceral responses to stressful
and emotionally provocative stimuli, based upon analysis of lesion effects
involving this area in humans and experimental animals. In a recent magnetic
resonance imaging (MRI) study of familial mood disorders, we demonstrated that
the mean grey matter volume of this cortex is abnormally reduced in subjects with
major depressive disorder (MDD) and bipolar disorder, irrespective of their
treatment status or current mood state. Moreover, in preliminary
histopathological assessments of subgenual PFC tissue taken post mortem from
subjects with MDD and bipolar disorder we obtained results suggesting that this
decrement in grey matter volume is associated with a reduction in glia without an
equivalent loss of neurons. The potential functional significance of these
neuroimaging and microscopic abnormalities is discussed with respect to evidence
that subgenual PFC dysfunction may disturb stress-related autonomic and
neuroendocrine responses and reward-related mesolimbic dopamine function.
These data may thus hold important implications for the development of neural
models of mood disorders that can account for the abnormal hedonic,
motivational, neuroendocrine, and autonomic manifestations evident in these
idiopathic conditions.
40. Driver, J.; Spence, C. Crossmodal attention. Curr-Opin-Neurobiol. 1998 Apr; 8(2):
245-53; ISSN: 0959-4388.
ENGLAND. Most selective attention research has considered only a single
sensory modality at a time, but in the real world, our attention must be
coordinated crossmodally. Recent studies reveal extensive crossmodal links in
attention across the various modalities (i.e. audition, vision, touch and
proprioception). Attention typically shifts to a common location across the
modalities, despite the vast differences in their initial coding of space. These
spatial synergies in attention can be maintained even when receptors are realigned
across the modalities by changes in posture. Some crossmodal integration can arise
preattentively. The mechanisms underlying these crossmodal links can be
examined in a convergent manner by integrating behavioural studies of normal
subjects and brain-damaged patients with neuroimaging and neurophysiological
studies.
41. Driver, J.; Spence, C. Crossmodal attention. Curr-Opin-Neurobiol. 1998 Apr; 8(2):
245-53; ISSN: 0959-4388.
ENGLAND. Most selective attention research has considered only a single
sensory modality at a time, but in the real world, our attention must be
coordinated crossmodally. Recent studies reveal extensive crossmodal links in
attention across the various modalities (i.e. audition, vision, touch and
proprioception). Attention typically shifts to a common location across the
modalities, despite the vast differences in their initial coding of space. These
spatial synergies in attention can be maintained even when receptors are realigned
across the modalities by changes in posture. Some crossmodal integration can arise
preattentively. The mechanisms underlying these crossmodal links can be
examined in a convergent manner by integrating behavioural studies of normal
subjects and brain-damaged patients with neuroimaging and neurophysiological
studies.
42. Dugast, C.; Souliere, F.; Schmitt, P.; Casanovas, J. M.; Fattaccini, C. M.; Mocaer, E.;
Lesourd, M.; Renaud, B.; Artigas, F.; Hamon, M.; Chouvet, G. Is the potent 5-
HT1A receptor agonist, alnespirone (S-20499), affecting dopaminergic systems in
the rat brain? Eur-J-Pharmacol. 1998 Jun 5; 350(2-3): 171-80; ISSN: 0014-2999.
NETHERLANDS. The effects of the new methoxy-chroman 5-HT1A receptor
agonist, alnespirone (S-20499), on the dopamine systems in the rat brain were
assessed in vivo by means of electrophysiological and neurochemical techniques.
Cumulative doses of alnespirone (0.032-4.1 mg kg(-1), i.v.) did not modify the
spontaneous firing rate of dopamine neurons in the substantia nigra as well as in
the ventral tegmental area. The local application of alnespirone (0.1-10 microM)
by reverse microdialysis into the dorsal striatum did not affect the dopamine
output but induced a moderate, although dose-independent, increase of 5-HT (5-
hydroxytryptamine, serotonin) concentrations in the dialysate. As expected of a
5-HT1A receptor agonist, intraperitoneal (i.p.) administration of alnespirone at 2-
32 mg kg(-1) markedly decreased 5-HT turnover in the striatum. Parallel
measurements of dopamine turnover showed that alnespirone exerted no effect
except at the highest dose (32 mg kg(-1), i.p.) for which a significant increase was
observed. Interestingly, both alnespirone-induced reduction in 5-HT turnover and
increase in dopamine turnover could be prevented by pretreatment with the
selective 5-HT1A receptor antagonist WAY-100635 (N-[2-[4-(2-
methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexa ne carboxamide).
Altogether, these data indicate that alnespirone does not exert any direct influence
on central dopamine systems. The enhanced dopamine turnover due to
alnespirone at high dose appeared to result from 5-HT1A receptor stimulation,
further supporting the idea that this receptor type may play a key role in 5-HT-
dopamine interactions in brain.. EC 4.1.1.-; 0; 0; 0; 0; 0; 112692-38-3; 143413-
68-7; 51-61-6; 56-69-9; 63-84-3.
43. Duke, C. C.; Crewther, S. G.; Lawson, M. L.; Henry, L.; Kiely, P. M.; West, S. J.;
Crewther, D. P. Motion perception in global versus local attentional modes. Aust-
N-Z-J-Ophthalmol. 1998 May; 26 Suppl 1: S114-6; ISSN: 0814-9763.
AUSTRALIA. PURPOSE: Global and local attention are two forms of selective
visual attention which activate different areas of the cortex. The purpose of this
experiment was to test subjects' motion coherence thresholds under conditions of
global or local attention. It was hypothesized that thresholds in global attention
would be lower than in local attention. METHODS: Eleven adult subjects
participated in this study. Subjects were required to identify direction of motion
at variable coherence levels, while simultaneously identifying either the global or
local letter. Three velocities were used for coherent motion (3, 6 and 18 degrees/s).
RESULTS: The results showed that letter identification (global or local) did not
significantly affect motion coherence thresholds; however, thresholds were
significantly higher at 18 degrees/s than in the lower velocities. CONCLUSIONS:
These results highlight the attentional limitations of visual information shown by
increased motion coherence thresholds when two objects must be identified
simultaneously in a brief display.
44. Duke, C. C.; Crewther, S. G.; Lawson, M. L.; Henry, L.; Kiely, P. M.; West, S. J.;
Crewther, D. P. Motion perception in global versus local attentional modes. Aust-
N-Z-J-Ophthalmol. 1998 May; 26 Suppl 1: S114-6; ISSN: 0814-9763.
AUSTRALIA. PURPOSE: Global and local attention are two forms of selective
visual attention which activate different areas of the cortex. The purpose of this
experiment was to test subjects' motion coherence thresholds under conditions of
global or local attention. It was hypothesized that thresholds in global attention
would be lower than in local attention. METHODS: Eleven adult subjects
participated in this study. Subjects were required to identify direction of motion
at variable coherence levels, while simultaneously identifying either the global or
local letter. Three velocities were used for coherent motion (3, 6 and 18 degrees/s).
RESULTS: The results showed that letter identification (global or local) did not
significantly affect motion coherence thresholds; however, thresholds were
significantly higher at 18 degrees/s than in the lower velocities. CONCLUSIONS:
These results highlight the attentional limitations of visual information shown by
increased motion coherence thresholds when two objects must be identified
simultaneously in a brief display.
45. Edwards, M.; Badcock, D. R.; Smith, A. T. Independent speed-tuned global-motion
systems. Vision-Res. 1998 Jun; 38(11): 1573-80; ISSN: 0042-6989.
ENGLAND. Several experiments were conducted to investigate the role of speed
in global-motion processing; the extraction of the direction of motion of a small
subset of coherently-moving (signal) dots in a stimulus in which the other (noise)
dots move in random directions. The specific aim of the experiments was to
determine whether multiple speed-tuned global-motion systems exist. The results
of these experiments are: (1) when the signal dots were chosen from a group of
dots moving at 1.2 degrees s-1, the speed of additional-noise dots had to be below
4.8 degrees s-1 for them to affect global-motion extraction; (2) the addition of
static dots did not impair the extraction of a global-motion signal carried by dots
moving at 1.2 degrees s-1; (3) noise dots moving at 1.2 degrees s-1 impaired the
extraction of a global-motion signal from dots moving at 10.8 degrees s-1, though
not to the same extent as dots moving at a higher speed; and (4) these results were
dependent upon speed, not spatial-step size or luminance contrast. These results
are interpreted as indicating that global-motion extraction occurs within at least
two independent speed tuned systems. One of these systems is sensitive to high
speeds and the other to low speeds.
46. Edwards, M.; Badcock, D. R.; Smith, A. T. Independent speed-tuned global-motion
systems. Vision-Res. 1998 Jun; 38(11): 1573-80; ISSN: 0042-6989.
ENGLAND. Several experiments were conducted to investigate the role of speed
in global-motion processing; the extraction of the direction of motion of a small
subset of coherently-moving (signal) dots in a stimulus in which the other (noise)
dots move in random directions. The specific aim of the experiments was to
determine whether multiple speed-tuned global-motion systems exist. The results
of these experiments are: (1) when the signal dots were chosen from a group of
dots moving at 1.2 degrees s-1, the speed of additional-noise dots had to be below
4.8 degrees s-1 for them to affect global-motion extraction; (2) the addition of
static dots did not impair the extraction of a global-motion signal carried by dots
moving at 1.2 degrees s-1; (3) noise dots moving at 1.2 degrees s-1 impaired the
extraction of a global-motion signal from dots moving at 10.8 degrees s-1, though
not to the same extent as dots moving at a higher speed; and (4) these results were
dependent upon speed, not spatial-step size or luminance contrast. These results
are interpreted as indicating that global-motion extraction occurs within at least
two independent speed tuned systems. One of these systems is sensitive to high
speeds and the other to low speeds.
47. Erhardt, S.; Andersson, B.; Nissbrandt, H.; Engberg, G. Inhibition of firing rate and
changes in the firing pattern of nigral dopamine neurons by gamma-
hydroxybutyric acid (GHBA) are specifically induced by activation of GABA(B)
receptors. Naunyn-Schmiedebergs-Arch-Pharmacol. 1998 Jun; 357(6): 611-9;
ISSN: 0028-1298.
GERMANY. Previous studies have shown that administration of gamma-
hydroxybutyric acid (GHBA) or the GABA(B) receptor agonist baclofen are
associated with a decrease in firing rate, a regularisation of firing pattern and a
decrease in burst activity of midbrain dopamine (DA) neurons in the substantia
nigra (SN). In the present study we compared the ability of the novel GABA(B)
receptor antagonist SCH 50911 and the selective antagonist of GHBA binding
sites, NCS-382, to antagonise the effects of baclofen or GHBA, respectively, on
the neuronal activity of DA neurons in anaesthetised rats. SCH 50911 (75 mg/kg,
i.v.) was found to antagonise the decrease in firing rate, the regularisation of firing
rhythm and the decrease of burst activity in DA cells, induced by baclofen (1-32
mg/kg, i.v.) or GHBA (12.5-1600 mg/kg, i.v.). NCS-382 (100 mg/kg, i.v.) did not
affect the baclofen-induced changes in neuronal activity. Neither was the drug able
to influence the GHBA-induced alterations in firing rate or in burst activity,
although NCS-382 to some extent antagonised the regularisation of the firing
pattern observed following low doses of GHBA (< or =100 mg/kg). The results of
the present study give further support for the notion that the GHBA-induced
changes in neuronal activity of nigral dopamine neurons are mediated by
stimulation of GABA(B) receptors.. 0; 0; 0; 0; 0; 0; 0; 0; 1134-47-0; 131733-92-
1; 502-85-2; 51-61-6.
48. Figlewicz, D. P.; Patterson, T. A.; Johnson, L. B.; Zavosh, A.; Israel, P. A.; Szot, P.
Dopamine transporter mRNA is increased in the CNS of Zucker fatty (fa/fa) rats.
Brain-Res-Bull. 1998 Jun; 46(3): 199-202; ISSN: 0361-9230.
UNITED-STATES. The obese Zucker fa/fa rat is characterized by
hyperinsulinemia, obesity, and altered monoamine metabolism in the central
nervous system (CNS). It has been proposed that the changes in monoamine
metabolism may contribute to the metabolic pathophysiology of these animals.
Because it has been reported that insulin may regulate the catecholamine reuptake
transporters, which terminate monoaminergic synaptic signaling, in the present
study we tested whether messenger ribonucleic acid (mRNA) levels for the
noradrenergic (NE) or dopaminergic (DA) transporters were altered in obese fa/fa
vs. lean Fa/Fa Zucker rats. We found significantly elevated DA transporter levels
in both the ventral tegmental area/substantia nigra pars compacta (VTA/SNc) and
zona incerta (ZI) of obese Zucker fa/fa rats (164 +/- 24% of control levels, p =
.024; and 316 +/- 61% of control levels, p = .019, respectively). Measurement of
mRNA for tyrosine hydroxylase (TH), the rate-limiting enzyme for NE and DA
synthesis revealed no effect of the fa gene in either NE or DA neurons. These
findings suggest that increased DA clearance, and perhaps decreased DA signaling,
may occur in the obese Zucker fa/fa rat.. EC 1.14.16.2; 0; 0; 0.
49. Fushimi, M.; Niiyama, Y.; Fujiwara, R.; Satoh, N.; Hishikawa, Y. Some sensory
stimuli generate spontaneous K-complexes. Psychiatry-Clin-Neurosci. 1998 Apr;
52(2): 150-2; ISSN: 1323-1316.
AUSTRALIA. The present study was performed in order to determine whether
spontaneous K-complex are induced by sensory stimuli. Electroencephalogram
(EEG) segments in stage 2 sleep containing an evoked K-complex or spontaneous
K-complex were separately averaged with respect to the peak of N300, one of the
main components constituting the K-complex. Small negative and positive
components were found immediately before the main components of spontaneous
K-complex in averaged EEG. These two components were judged to correspond
to N100 and P200 induced by the sound stimulus. The present findings suggest
that the spontaneous K-complex is not a spontaneous phenomenon but that it is
induced by sensory stimuli.
50. Fushimi, M.; Niiyama, Y.; Fujiwara, R.; Satoh, N.; Hishikawa, Y. Some sensory
stimuli generate spontaneous K-complexes. Psychiatry-Clin-Neurosci. 1998 Apr;
52(2): 150-2; ISSN: 1323-1316.
AUSTRALIA. The present study was performed in order to determine whether
spontaneous K-complex are induced by sensory stimuli. Electroencephalogram
(EEG) segments in stage 2 sleep containing an evoked K-complex or spontaneous
K-complex were separately averaged with respect to the peak of N300, one of the
main components constituting the K-complex. Small negative and positive
components were found immediately before the main components of spontaneous
K-complex in averaged EEG. These two components were judged to correspond
to N100 and P200 induced by the sound stimulus. The present findings suggest
that the spontaneous K-complex is not a spontaneous phenomenon but that it is
induced by sensory stimuli.
51. Garcia Perez, M. A.; Sierra Vazquez, V. The optimal motion stimulus: comments on
Watson and Turano (1995) [letter]. Vision-Res. 1998 Jun; 38(11): 1611-21; ISSN:
0042-6989.
ENGLAND. Watson and Turano (Vision Research 1995;35:325-336) described
experimental research aimed at determining the motion stimulus that the visual
system detects best. They reported conflicting results in the determination of the
optimal spatial size and they interpreted them as an effect of probability
summation. They also reported disagreement with earlier results of Watson et al.
(Nature 1983;302:419-422). This study shows (i) that probability summation is
not responsible for those results and (ii) that they can be explained as a
consequence of the method that was used to search for the optimal stimulus.
52. Garcia Perez, M. A.; Sierra Vazquez, V. The optimal motion stimulus: comments on
Watson and Turano (1995) [letter]. Vision-Res. 1998 Jun; 38(11): 1611-21; ISSN:
0042-6989.
ENGLAND. Watson and Turano (Vision Research 1995;35:325-336) described
experimental research aimed at determining the motion stimulus that the visual
system detects best. They reported conflicting results in the determination of the
optimal spatial size and they interpreted them as an effect of probability
summation. They also reported disagreement with earlier results of Watson et al.
(Nature 1983;302:419-422). This study shows (i) that probability summation is
not responsible for those results and (ii) that they can be explained as a
consequence of the method that was used to search for the optimal stimulus.
53. Gash, D. M.; Zhang, Z.; Gerhardt, G. Neuroprotective and neurorestorative
properties of GDNF. Ann-Neurol. 1998 Sep; 44(3 Suppl 1): S121-5; ISSN: 0364-
5134.
UNITED-STATES. Glial cell line-derived neurotrophic factor (GDNF) promotes
recovery of the injured nigrostriatal dopamine system and improves motor
functions in both rodent and nonhuman primate models of Parkinson's disease
(PD). The neurorestorative effects of a single administration of GDNF last for at
least 1 month and can be maintained in rhesus monkeys by monthly injections.
Adult midbrain dopamine neurons stimulated by GDNF show increased cell size,
neurite extent, and expression of phenotypic markers. In parkinsonian nonhuman
primates, GDNF treatment improves three of the cardinal features of PD:
bradykinesia, rigidity, and postural instability. Although intracerebral
administration is necessary because of the blood-brain barrier, intraventricular,
intrastriatal, and intranigral routes of administration have been found to be
efficacious in rodents and nonhuman primates. GDNF also induces
neuroprotective changes in dopamine neurons which are active within hours after
trophic factor administration. The powerful neuroprotective and neurorestorative
properties of GDNF seen in preclinical studies suggest that trophic factors may
play an important role in treating PD.. 0; 0; 0; 0; 51-61-6.
54. Gerber, B.; Smith, B. H. Visual modulation of olfactory learning in honeybees. J-Exp-
Biol. 1998 Jul; 201( Pt 14): 2213-7; ISSN: 0022-0949.
ENGLAND. We use classical conditioning of the honeybee (Apis mellifera)
proboscis extension reflex with a visual (A) and an olfactory (X) conditioned
stimulus in a blocking paradigm. Typically, learning about one element (X) of a
compound (AX) is decreased (blocked) if the other component (A) has previously
been rewarded alone. Our results show that visual pretraining did not produce
blocking in honeybees: instead, forward pairings of A with a reward increased
subsequent learning about X relative to a backward pairing control. This finding
violates the independence assumption, which holds that elements of inter-modal
compound stimuli change associative strength independently of each other.
Furthermore, it is at odds with common theories of conditioning that predict
blocking and assume that the elements of a compound stimulus rely on one
common internal reinforcing signal. Taking the functional anatomy of the
honeybee brain into account, we suggest that vision and olfaction may not rely on
the same internal reinforcing signal; compound interactions might thus reflect the
wiring of the honeybee nervous system and the biological significance of different
sensory modalities during natural behaviour.
55. Gerber, B.; Smith, B. H. Visual modulation of olfactory learning in honeybees. J-Exp-
Biol. 1998 Jul; 201( Pt 14): 2213-7; ISSN: 0022-0949.
ENGLAND. We use classical conditioning of the honeybee (Apis mellifera)
proboscis extension reflex with a visual (A) and an olfactory (X) conditioned
stimulus in a blocking paradigm. Typically, learning about one element (X) of a
compound (AX) is decreased (blocked) if the other component (A) has previously
been rewarded alone. Our results show that visual pretraining did not produce
blocking in honeybees: instead, forward pairings of A with a reward increased
subsequent learning about X relative to a backward pairing control. This finding
violates the independence assumption, which holds that elements of inter-modal
compound stimuli change associative strength independently of each other.
Furthermore, it is at odds with common theories of conditioning that predict
blocking and assume that the elements of a compound stimulus rely on one
common internal reinforcing signal. Taking the functional anatomy of the
honeybee brain into account, we suggest that vision and olfaction may not rely on
the same internal reinforcing signal; compound interactions might thus reflect the
wiring of the honeybee nervous system and the biological significance of different
sensory modalities during natural behaviour.
56. Ghee, M.; Baker, H.; Miller, J. C.; Ziff, E. B. AP-1, CREB and CBP transcription
factors differentially regulate the tyrosine hydroxylase gene. Brain-Res-Mol-
Brain-Res. 1998 Mar 30; 55(1): 101-14; ISSN: 0169-328X.
NETHERLANDS. The tyrosine hydroxylase (TH) gene encodes the rate-limiting
enzyme in the biosynthesis of catecholamines. We have investigated the roles of
two elements of the TH promoter, the TH-'Fat Specific Element' (TH-FSE) which
binds the Fos-Jun complex, and the cAMP Response Element (CRE), which
binds CREB and the co-activator protein, CREB Binding Protein (CBP) in
regulating TH gene transcription. In PC12 cells, the TH-FSE was required for
induction by NGF while the CRE was required for induction by cAMP. We show
that both elements can function independently and contribute strongly to TH
promoter basal activity in PC12 cells. We employed transient expression in the
F9 teratocarcinoma cell line to vary experimentally the levels of the nuclear
regulators implicated in TH control by the PC12 studies. In F9 cells, the TH
promoter was strongly activated by Fos and Jun, and by PKA-stimulated CREB
protein. In F9 and NIH3T3 cells, CBP, a co-activator which targets Fos-Jun and
PKA-stimulated CREB, also induced the TH promoter. Immunohistochemical
studies in rat brain regions enriched in dopaminergic neurons, including the
midbrain and olfactory bulb (OB), suggest that Fos-Jun and CREB make
differential contributions to TH gene activity in different tissues. Whereas changes
in Fos protein levels parallel decreases in TH protein upon olfactory deprivation,
CBP levels remain unchanged. This suggests that CRE-associated factors,
including CBP, are not major regulators in the OB. In contrast, the presence of
CREB and the absence of Fos immunoreactivity in midbrain dopaminergic cells
suggests that the CRE is the primary regulator in this region.. EC 1.14.16.2; EC
2.3.1.28; EC 2.7.10.-; 0; 0; 0; 0; 0; 0; 0; 0; 51-61-6; 60-92-4.
57. Gillner, S.; Mallot, H. A. Navigation and acquisition of spatial knowledge in a virtual
maze. J-Cogn-Neurosci. 1998 Jul; 10(4): 445-63; ISSN: 0898-929X.
UNITED-STATES. Spatial behavior in humans and animals includes a wide
variety of behavioral competences and makes use of a large number of sensory
cues. Here we studied the ability of human subjects to search locations, to find
shortcuts and novel paths, to estimate distances between remembered places, and
to draw sketch maps of the explored environment; these competences are related
to goal-independent memory of space, or cognitive maps. Information on spatial
relations was restricted to two types: a visual motion sequence generated by
simulated movements in a virtual maze and the subject's own movement decisions
defining the path through the maze. Visual information was local (i.e., no global
landmarks or compass information was provided). Other position and movement
information (vestibular or proprioceptive) was excluded. The amount of visual
information provided was varied over four experimental conditions. The results
indicate that human subjects are able to learn a virtual maze from sequences of
local views and movements. The information acquired is local, consisting of
recognized positions and movement decisions associated to them. Although
simple associations of this type can be shown to be present in some subjects,
more complete configurational knowledge is acquired as well. The results are
discussed in a view-based framework of navigation and the representation of
spatial knowledge by means of a view graph.
58. Gillner, S.; Mallot, H. A. Navigation and acquisition of spatial knowledge in a virtual
maze. J-Cogn-Neurosci. 1998 Jul; 10(4): 445-63; ISSN: 0898-929X.
UNITED-STATES. Spatial behavior in humans and animals includes a wide
variety of behavioral competences and makes use of a large number of sensory
cues. Here we studied the ability of human subjects to search locations, to find
shortcuts and novel paths, to estimate distances between remembered places, and
to draw sketch maps of the explored environment; these competences are related
to goal-independent memory of space, or cognitive maps. Information on spatial
relations was restricted to two types: a visual motion sequence generated by
simulated movements in a virtual maze and the subject's own movement decisions
defining the path through the maze. Visual information was local (i.e., no global
landmarks or compass information was provided). Other position and movement
information (vestibular or proprioceptive) was excluded. The amount of visual
information provided was varied over four experimental conditions. The results
indicate that human subjects are able to learn a virtual maze from sequences of
local views and movements. The information acquired is local, consisting of
recognized positions and movement decisions associated to them. Although
simple associations of this type can be shown to be present in some subjects,
more complete configurational knowledge is acquired as well. The results are
discussed in a view-based framework of navigation and the representation of
spatial knowledge by means of a view graph.
59. Gorelick, A. B.; Koshy, S. S.; Hooper, F. G.; Bennett, T. C.; Chey, W. D.; Hasler, W.
L. Differential effects of amitriptyline on perception of somatic and visceral
stimulation in healthy humans. Am-J-Physiol. 1998 Sep; 275(3 Pt 1): G460-6;
ISSN: 0002-9513.
UNITED-STATES. Tricyclic antidepressants treat chronic pain both in patients
with somatic illness and with functional bowel disorders. We compared the effects
of amitriptyline on perception of cutaneous and gastrointestinal stimulation to
assess differential analgesic effects of tricyclics on somatic and visceral pain.
Cutaneous electrical stimulation and rectal and esophageal distension were
performed before and after 21 days of double-blind 50 mg amitriptyline vs.
placebo in healthy volunteers. Amitriptyline increased currents that elicited
cutaneous threshold, moderate discomfort, and moderate pain compared with
basal (P < 0.05), whereas placebo had no effect. Amitriptyline had no effect on
perception of rectal and esophageal distension and did not alter luminal
compliance; thus the lack of effect on perception is not due to altered visceral
elastic wall properties. In conclusion, amitriptyline reduces perception of
cutaneous stimulation but does not alter visceral perception or compliance. This
investigation demonstrates differential effects of tricyclics on somatic and visceral
afferent function in healthy humans and provides insight into mechanisms of
action in chronic pain both from somatic disease and from functional bowel
disorders.. 50-48-6.
60. Gorelick, A. B.; Koshy, S. S.; Hooper, F. G.; Bennett, T. C.; Chey, W. D.; Hasler, W.
L. Differential effects of amitriptyline on perception of somatic and visceral
stimulation in healthy humans. Am-J-Physiol. 1998 Sep; 275(3 Pt 1): G460-6;
ISSN: 0002-9513.
UNITED-STATES. Tricyclic antidepressants treat chronic pain both in patients
with somatic illness and with functional bowel disorders. We compared the effects
of amitriptyline on perception of cutaneous and gastrointestinal stimulation to
assess differential analgesic effects of tricyclics on somatic and visceral pain.
Cutaneous electrical stimulation and rectal and esophageal distension were
performed before and after 21 days of double-blind 50 mg amitriptyline vs.
placebo in healthy volunteers. Amitriptyline increased currents that elicited
cutaneous threshold, moderate discomfort, and moderate pain compared with
basal (P < 0.05), whereas placebo had no effect. Amitriptyline had no effect on
perception of rectal and esophageal distension and did not alter luminal
compliance; thus the lack of effect on perception is not due to altered visceral
elastic wall properties. In conclusion, amitriptyline reduces perception of
cutaneous stimulation but does not alter visceral perception or compliance. This
investigation demonstrates differential effects of tricyclics on somatic and visceral
afferent function in healthy humans and provides insight into mechanisms of
action in chronic pain both from somatic disease and from functional bowel
disorders.. 50-48-6.
61. Gros, B. L.; Blake, R.; Hiris, E. Anisotropies in visual motion perception: a fresh
look. J-Opt-Soc-Am-A-Opt-Image-Sci-Vis. 1998 Aug; 15(8): 2003-11; ISSN:
1084-7529.
UNITED-STATES. We measured motion-detection and motion-discrimination
performance for different directions of motion, using stochastic motion sequences.
Random-dot cinematograms containing 200 dots in a circular aperture were used
as stimuli in a two-interval forced-choice procedure. In the motion-detection
experiment, observers judged which of two intervals contained weak coherent
motion, the other internal containing random motion only. In the direction-
discrimination experiment, observers viewed a standard direction of motion
followed by comparison motion in a slightly different direction. Observers
indicated whether the comparison was clockwise or counterclockwise, relative to
the standard. Twelve directions of motion were tested in the detection task and
five standard directions (three cardinal directions and two oblique directions) in
the discrimination task. Detection thresholds were invariant with direction of
motion, but direction-discrimination thresholds were significantly higher for
motion in oblique directions, even at low-coherence levels. Results from control
conditions ruled out monitor artifacts and indicate that the oblique effect is
relative to retinal coordinates. These results have broad implications for
computational and physiological models of motion perception.
62. Gros, B. L.; Blake, R.; Hiris, E. Anisotropies in visual motion perception: a fresh
look. J-Opt-Soc-Am-A-Opt-Image-Sci-Vis. 1998 Aug; 15(8): 2003-11; ISSN:
1084-7529.
UNITED-STATES. We measured motion-detection and motion-discrimination
performance for different directions of motion, using stochastic motion sequences.
Random-dot cinematograms containing 200 dots in a circular aperture were used
as stimuli in a two-interval forced-choice procedure. In the motion-detection
experiment, observers judged which of two intervals contained weak coherent
motion, the other internal containing random motion only. In the direction-
discrimination experiment, observers viewed a standard direction of motion
followed by comparison motion in a slightly different direction. Observers
indicated whether the comparison was clockwise or counterclockwise, relative to
the standard. Twelve directions of motion were tested in the detection task and
five standard directions (three cardinal directions and two oblique directions) in
the discrimination task. Detection thresholds were invariant with direction of
motion, but direction-discrimination thresholds were significantly higher for
motion in oblique directions, even at low-coherence levels. Results from control
conditions ruled out monitor artifacts and indicate that the oblique effect is
relative to retinal coordinates. These results have broad implications for
computational and physiological models of motion perception.
63. Gu, M.; Owen, A. D.; Toffa, S. E.; Cooper, J. M.; Dexter, D. T.; Jenner, P.;
Marsden, C. D.; Schapira, A. H. Mitochondrial function, GSH and iron in
neurodegeneration and Lewy body diseases. J-Neurol-Sci. 1998 Jun 11; 158(1):
24-9; ISSN: 0022-510X.
NETHERLANDS. The cause of neuronal loss in patients with idiopathic
Parkinson's disease is unknown. Oxidative stress and complex I deficiency have
both been identified in the substantia nigra in Parkinson's disease but their place in
the sequence of events resulting in dopaminergic cell death is uncertain. We have
analysed respiratory chain activity, iron and reduced glutathione concentrations in
Parkinson's disease substantia innominata and in the cingulate cortex of patients
with Parkinson's disease, Alzheimer's disease and dementia with Lewy bodies to
investigate their association with neuronal death and Lewy body formation. No
abnormalities of mitochondrial function, iron or reduced glutathione levels were
identified in Parkinson's disease substantia innominata or cingulate cortex.
Mitochondrial function also appeared to be unchanged in cingulate cortex from
patients with Alzheimer's disease and from patients with dementia with Lewy
bodies, however, iron concentrations were mildly increased in both, and reduced
glutathione decreased only in Alzheimer's disease. These results confirm the
anatomic specificity of the complex I deficiency and decreased levels of reduced
glutathione within the Parkinson's disease brain and suggest that these parameters
are not associated with cholinergic cell loss in Parkinson's disease nor with Lewy
body formation in this or other diseases. We propose that our data support a
'two-hit' hypothesis for the cause of neuronal death in Parkinson's disease.. EC
1.6.99.2; 0; 51-61-6; 70-18-8; 7439-89-6.
64. Harden, D. G.; King, D.; Finlay, J. M.; Grace, A. A. Depletion of dopamine in the
prefrontal cortex decreases the basal electrophysiological activity of mesolimbic
dopamine neurons. Brain-Res. 1998 May 25; 794(1): 96-102; ISSN: 0006-8993.
NETHERLANDS. One hypothesis regarding the etiology of schizophrenia
proposes that disruption of the dopaminergic innervation of the prefrontal cortex
leads to an increase in dopamine (DA) transmission in subcortical regions. In the
present study, we examined the effect of 6-hydroxydopamine lesions of the
medial prefrontal cortex (mPFC) dopamine innervation on the spontaneous
electrophysiological activity of ventral tegmental DA neurons recorded in vivo.
DA cell activity was assessed along three dimensions: (1) the relative proportion
of DA neurons exhibiting spontaneous activity, (2) their basal firing rate, and (3)
the mean percentage of spikes fired in bursts. In lesioned rats, DA neurons in the
ventral tegmental area (VTA) exhibited a significantly slower mean firing rate, as
well as a significant reduction in the percentage of spikes fired in bursts relative to
controls. In contrast, depletion of DA in the mPFC did not have a significant
effect on the relative proportion of VTA DA neurons exhibiting spontaneous
activity. We suggest that by reducing the basal electrophysiological activity of
VTA DA neurons, mPFC DA depletion may lead to an increase in the level of
responsivity of the system to excitatory stimuli. Thus, the magnitude of increase
in action potential-dependent DA release that occurs in response to a challenge
may be augmented in lesioned rats. Copyright 1998 Elsevier Science B.V. All
rights reserved.. 1199-18-4; 51-61-6.
65. Heidbreder, C.; Feldon, J. Amphetamine-induced neurochemical and locomotor
responses are expressed differentially across the anteroposterior axis of the core
and shell subterritories of the nucleus accumbens. Synapse. 1998 Aug; 29(4): 310-
22; ISSN: 0887-4476.
UNITED-STATES. The administration of psychostimulants increases dopamine
(DA) release within the nucleus accumbens (NAC), a terminal projection site of
mesolimbic DA neurons, originating in the ventral tegmental area (VTA). Recent
evidence demonstrates that two subdivisions of the NAC, the dorsolateral core
and the ventromedial shell, can be distinguished by morphological and
immunohistochemical differences, as well as by their distinct anatomical
connections. It has been suggested that these two subregions subserve different
functions that are related to goal-directed behaviors, stimulus-reward associations,
and reinforcement induced by addictive drugs. The shell region, in particular,
modulates inputs from the limbic system, whereas the core is preferentially
innervated by nuclei that process motor information. In the present study, we
sought to investigate if (1) the direct infusion of d-amphetamine (AMPH) by
reverse microdialysis into either the core or shell of the NAC across its
anteroposterior axis differentially affects dialysate DA and 5-HT levels, and (2)
these subterritories also subserve different behavioral functions. Following the
determination of basal DA and 5-HT levels, four increasing concentrations of
AMPH (0.05, 0.10, 0.50, 1.00 microM) were substituted for the dialysis
perfusate for 60 min each. Movement units were detected by an infrared sensor
and were transmitted through a motion interface to an activity monitor analyzer.
AMPH produced a dose-dependent increase in locomotor activity after
microinfusion into either the rostral shell, caudal shell or core of the NAC. The
potency of the AMPH-induced locomotor activating effect was significantly
higher in the rostral shell of the NAC compared with the caudal shell and the core.
The lowest concentrations of AMPH (0.05, 0.1 microM) produced an equipotent
decrease in dialysate DA in either the rostral shell, caudal shell, or core. At 1.0
microM, however, AMPH selectively increased DA in the rostral shell, whereas