Abstract/Details

The role of substantia nigra pars reticulata and subthalamic nucleus in mediating posture, movement, and seizure susceptibility: An interspecies comparison between rat and monkey


2001 2001

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Abstract (summary)

The neurons of the substantia nigra pars reticulata (SNpr) provide neuronal output from the basal ganglia and are subject to control from the subthalamic nucleus (STN). Most of the knowledge concerning the functional neuroanatomy of this system derives from rodent studies. The present series of studies sought to extend findings about basal ganglia function gained from rodent studies into primates.

Inhibition of rodent SNpr function is known to evoke contralaterally-directed postural and motor asymmetry, and to produce an anticonvulsant effect. To date there have been no site-specific behavioral studies of inhibition of rodent STN function. The first goal of these studies was to evaluate the site-specific effects of focal inhibition of rat STN. Microinjection of a GABAA receptor agonist (muscimol, 200 pmol) into rat STN produced a site-specific, contralaterally-directed postural asymmetry and protected against limbic motor seizures. These effects are consistent with convergent evidence that in the rat the STN provides an excitatory projection to SNpr.

The second aim of the present experiments was to extend these findings into the non-human primate by injecting muscimol (9nmol) into various locations within SNpr or STN in freely moving monkeys. Depending upon the location within SNpr, unilateral injections of muscimol induced contralateral choreiform dyskinesias, or contralaterally-directed dystonic postures. Furthermore, bilateral microinjection of muscimol (4.5 nmol) into SNpr protected against focally-evoked seizure manifestations. These effects are similar in nature to effects obtained with inhibition of the SNpr in the rat.

In contrast to results in the rat, however, injections of muscimol into the primate STN produced no behavioral abnormalities, whereas injections of GABA antagonist (bicuculline, 20 nmol) evoked contralateral hemiballistic dyskinesias. These findings suggest that unlike the rat, the primate STN exerts a negative influence on SNpr vis a vis the control of posture and movement, and argue against the direct extrapolation of results obtained from rodents to primates. Further, pharmacological manipulation of the monkey SNpr and STN provide novel models for producing dyskinetic and dystonic syndromes, and these areas may serve as targets for the treatment of such pathologies as Huntington's chorea, Parkinson's disease, dystonia, and epilepsy.

Indexing (details)


Subject
Neurology;
Pharmacology
Classification
0317: Neurology
0419: Pharmacology
Identifier / keyword
Health and environmental sciences; Biological sciences; Dystonia; GABA; Posture; Seizure; Substantia nigra pars reticulata; Subthalamic nucleus
Title
The role of substantia nigra pars reticulata and subthalamic nucleus in mediating posture, movement, and seizure susceptibility: An interspecies comparison between rat and monkey
Author
Dybdal, David J.
Number of pages
261
Publication year
2001
Degree date
2001
School code
0544
Source
DAI-B 62/05, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
9780493266121, 0493266127
Advisor
Gale, Karen
University/institution
Georgetown University Medical Center
University location
United States -- District of Columbia
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3016361
ProQuest document ID
275685953
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/275685953/abstract
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