Distribution and binding parameters of GABAA receptors in the thalamic nuclei of Macaca mulatta and changes caused by lesioning in the globus pallidus and reticular thalamic nucleus.

摘要

Ascending output from the basal ganglia to the primate motor thalamus is carried by GABAergic nigro- and pallido-thalamic pathways, which interact with intrinsic thalamic GABAergic systems represented in primates by local circuit neurons and axons of the reticular thalamic nucleus. Disease-triggered pathological processes in the basal ganglia can compromise any of these pathways either directly or indirectly, yet the effects of basal ganglia lesioning on its thalamic afferent-receiving territories has not been studied in primates. Two GABA(A) receptor ligands, [(3)H]muscimol and [(3)H]flunitrazepam, were used to study the distribution and binding properties of the receptor in intact monkeys, those with kainic acid lesions in the globus pallidus, and those with ibotenic acid lesions in the reticular nucleus using quantitative autoradiographic technique on cryostat sections of fresh frozen brain tissue. In control monkeys the binding affinities for [(3)H]muscimol averaged 50 nM in the thalamic nuclei and86 nM in the basal ganglia while the binding densities varied (maximum density of binding sites [Bmax] range of 99.4-1000.1 fmol/mg of tissue). Binding affinities and Bmax values for [(3)H]flunitrazepam averaged 2.02 nM and 81-113 fmol/mg of tissue, respectively. Addition of 100-microM GABA increased average affinity to 1.35 nM whereas Bmax values increased anywhere from 1-50% in different nuclei. Zolpidem (100 nM) decreased binding by 68-80%. Bmax values for both ligands were decreased at the two survival times in both medial and lateral globus pallidus implying involvement of both nuclei in the lesion. Statistically significant, 40% decrease (P=0.055) of Bmax for [(3)H]muscimol was observed in the ventral anterior nucleus pars densicellularis (VAdc, the main pallidal projection territory in the thalamus) 1 week after globus pallidus lesioning and a 36% decrease (P=0.017) 4 months post-lesioning. In contrast, [(3)H]flunitrazepam Bmax values in the VAdc of the same animals were increased by 23% (P=0.021) at 1week and 28% (P=0.005) 4 months postlesion, respectively. One week after the reticular nucleus lesioning, the binding densities of [(3)H]muscimol and [(3)H]flunitrazepam were decreased in the thalamic nuclei receiving projections from the lesioned reticular nucleus sector by approximately 50% (P<0.05) and 10-33% (P<0.05), respectively. The results suggest that different GABA(A) receptor subtypes are associated with different GABAergic systems in the thalamus which react differently to deafferentation.