GABA RECEPTORS IN THE THALAMUS

Summary

Principal Investigator: Yoland Smith
Affiliation: Emory University
Country: USA
Abstract: The basal ganglia and thalamus are interconnected through a series of loops that process and convey basal ganglia outflow to either frontal cortical regions via the ventral motor nuclei or back to the striatum via the caudal intralaminar group, namely the centre median (CM) and parafascicular (Pf) nuclei. Although the existence of a thalamostriatal system has long been established, the role of these projections in the functional circuitry of the basal ganglia remains enigmatic. For the first four years of this grant, we focused our interest on the sources and chemical nature of basal ganglia and brainstem synaptic inputs that control the activity of thalamostriatal neurons. Both the internal globus pallidus (GPi) and the substantia nigra pays reticulata (SNr) provide GABAergic afferents to specific regions of CM/Pf. In addition, the pedunculopontine tegmental nucleus (PPN) is the source of highly heterogeneous chemical inputs to CM/Pf, some of them co-localize GABA and acetylcholine. In addition, neurons in CM/Pf, as in most thalamic nuclei, are endowed with intrinsic GABAergic influences from the reticular nucleus and local interneurons. Electrophysiological data show that GABA plays a crucial role in regulating thalamic activity. However, the exact mechanisms by which GABA mediates its effects on thalamic neurons are complex and still matter of speculation. In order to further characterize this issue, we propose to use state-of- the-art immunocytochemical procedures at the electron microscopic level to elucidate the subsynaptic and subcellular localization of GABA-A and GABA-B receptors in the basal ganglia-receiving territories of the ventral motor thalamic nuclei and CM/PF in monkeys. Abnormal increased GABAergic outflow from the basal ganglia to the thalamus is a cardinal feature of Parkinson's disease pathophysiology. Such increased activity likely results in downregulation of postsynaptic GABA receptors in basal ganglia receiving thalamic nuclei. In order to elucidate this issue, another goal of this project is to compare the pattern of subsynaptic localization of GABA-A and GABA-B receptors in CM/Pf and ventral motor nuclei of normal monkeys and animal models of Parkinson's disease. This series of studies should provide a comprehensive analysis of GABA receptors localization at specific synaptic sites in basal ganglia-receiving thalamic nuclei in primates. Such information is critical for the interpretation of functional studies and a better understanding of the pathophysiological changes generated at pallidothalamic and nigrothalamic synapses in Parkinson's disease.
Funding Period: 1998-07-01 - 2006-04-30
more information: NIH RePORT

Top Publications

  1. ncbi GABA(B) receptors in the centromedian/parafascicular thalamic nuclear complex: an ultrastructural analysis of GABA(B)R1 and GABA(B)R2 in the monkey thalamus
    Rosa M Villalba
    Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30322, USA
    J Comp Neurol 496:269-87. 2006
  2. pmc Differential synaptology of vGluT2-containing thalamostriatal afferents between the patch and matrix compartments in rats
    Dinesh V Raju
    Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30322, USA
    J Comp Neurol 499:231-43. 2006
  3. pmc Glutamate and GABA receptors and transporters in the basal ganglia: what does their subsynaptic localization reveal about their function?
    A Galvan
    Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, USA
    Neuroscience 143:351-75. 2006
  4. pmc The thalamostriatal systems: anatomical and functional organization in normal and parkinsonian states
    Yoland Smith
    Yerkes National Primate Research Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, USA
    Brain Res Bull 78:60-8. 2009
  5. pmc Dopaminergic denervation and spine loss in the striatum of MPTP-treated monkeys
    Rosa M Villalba
    Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, NE Atlanta, GA 30322, USA
    Exp Neurol 215:220-7. 2009
  6. pmc Striatal spine plasticity in Parkinson's disease: pathological or not?
    Y Smith
    Yerkes National Primate Research Center and Department of Neurology, Emory University, Atlanta, GA 30322, USA
    Parkinsonism Relat Disord 15:S156-61. 2009

Scientific Experts

Detail Information

Publications6

  1. ncbi GABA(B) receptors in the centromedian/parafascicular thalamic nuclear complex: an ultrastructural analysis of GABA(B)R1 and GABA(B)R2 in the monkey thalamus
    Rosa M Villalba
    Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30322, USA
    J Comp Neurol 496:269-87. 2006
    ..Overall, these findings provide evidence for multiple sites where GABA(B) receptors could modulate GABAergic and glutamatergic transmission in the primate CM/PF complex...
  2. pmc Differential synaptology of vGluT2-containing thalamostriatal afferents between the patch and matrix compartments in rats
    Dinesh V Raju
    Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30322, USA
    J Comp Neurol 499:231-43. 2006
    ..These observations pave the way for understanding differential regulatory mechanisms of striatal outflow from the patch and matrix compartments by thalamostriatal afferents...
  3. pmc Glutamate and GABA receptors and transporters in the basal ganglia: what does their subsynaptic localization reveal about their function?
    A Galvan
    Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, USA
    Neuroscience 143:351-75. 2006
    ....
  4. pmc The thalamostriatal systems: anatomical and functional organization in normal and parkinsonian states
    Yoland Smith
    Yerkes National Primate Research Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, USA
    Brain Res Bull 78:60-8. 2009
    ..Although the available clinical evidence is encouraging, these procedures remain empirical at this stage because of the limited understanding of the thalamostriatal systems...
  5. pmc Dopaminergic denervation and spine loss in the striatum of MPTP-treated monkeys
    Rosa M Villalba
    Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, NE Atlanta, GA 30322, USA
    Exp Neurol 215:220-7. 2009
    ....
  6. pmc Striatal spine plasticity in Parkinson's disease: pathological or not?
    Y Smith
    Yerkes National Primate Research Center and Department of Neurology, Emory University, Atlanta, GA 30322, USA
    Parkinsonism Relat Disord 15:S156-61. 2009
    ..Future studies are needed to further characterize the mechanisms underlying striatal spine plasticity, and determine if it represents a pathological feature or compensatory process of PD...