GABAergic interneurons in the ventral motor and caudal intralaminar thalamic nuclei in primates: A potential source of GABAergic dysfunction in parkinsonism? Pubblico

Abstract

Despite extensive research, our understanding of the pathophysiology of the basal ganglia-thalamocortical functional circuitry in Parkinson’s Disease (PD) remains incomplete. Key features of parkinsonism are an increased GABAergic inhibition of the ventral motor thalamic nuclei, namely the ventral anterior and ventral lateral (VA/VL) nuclear group, and significant cell loss in the intralaminar centromedian and parafascicular nuclei (CM/Pf). According to current models of the basal ganglia circuitry, this increased thalamic inhibition originates from an abnormally overactive GABAergic tone from the basal ganglia output nuclei. A less studied source of GABA in the VA/VL are the inhibitory GABAergic interneurons. Because these interneurons are absent from the more easily studied rodent motor thalamus, little is known about their anatomy, function, or role in this thalamic region, and in the centromedian/parafascicular (CM/Pf) nuclear group, another main target of basal ganglia outflow in primates.

In order to further characterize the prevalence and potential degeneration of these interneurons in the motor thalamus of normal and parkinsonian monkeys, we performed an unbiased stereological count of interneurons and thalamocortical cells in VA/VL and CM/Pf by immunostaining with anti-GABA and anti-NeuN, respectively, in 3 control and 3 MPTP- (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-) treated parkinsonian monkeys. Data indicate that GABAergic interneurons account 12-14% of neurons in the basal ganglia-receiving motor thalamus (BGMT), 19-20% of neurons in the cerebellar-receiving motor thalamus (CbMT), 9-10% of neurons in the CM, and 7-8% of neurons in the Pf, without any significant difference between control and parkinsonian monkeys. Results of this study set the stage for a deeper understanding of the functional integration of GABAergic interneurons in the physiology and pathophysiology of the basal ganglia-thalamocortical circuitry in normal and parkinsonian state.

Table of Contents

Table of Contents

Introduction………………………………………………………………………………………..1

Materials and Methods…………………………………………………………………………….7

Results……………………………………………………………………………………………15

Discussion……………………………………………………………………………...………...21

References………………………………………………………………………………………..34

Tables & Figures:

Table 1…………………………………………………………………………………….8

Table 2…………………………………………………………………………………...11

Figure 1…………………………………………………………………………………..11

Figure 2…………………………………………………………………………………..13

Table 3…………………………………………………………………………………...16

Figure 3…………………………………………………………………………………..17

Figure 4…………………………………………………………………………………..19

Figure 5…………………………………………………………………………………..20

About this Master's Thesis

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School	Laney Graduate School
Department	Biological and Biomedical Sciences
Subfield / Discipline	Neuroscience
Degree	M.S.
Submission	Master's Thesis
Language	English
Research Field	Biology, Neuroscience
Parola chiave	GABA Primate Stereology Parkinson's Disease
Committee Chair / Thesis Advisor	John Hepler, Emory University Yoland Smith, Emory University
Committee Members	Francisco Alvarez, Emory University Yoland Smith, Emory University Leah Roesch, Emory University Adriana Galvan, Emory University

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