Glutamic Acid Decarboxylase Isoform 65 Immunoreactivity in the Motor Thalamus of Humans and Monkeys: γ-Aminobutyric Acidergic Connections and Nuclear Delineations

The neurotransmitter gamma-aminobutyric acid (GABA) plays an important role in the motor thalamic nuclei. This report analyzes the distribution of the GABA-producing enzyme glutamic acid decarboxylase isoform 65 (GAD65), stained with monoclonal antibody, in human and rhesus monkey thalami and compares it with staining patterns of some widely used cytoskeletal and calcium binding protein markers. GAD65 immunoreactivity distinctly labeled two systems: fibers and terminals of basal ganglia thalamic afferents and local circuit neurons, revealing fine features of GABAergic circuitry in the human thalamus. Gross distribution patterns of GAD65 were identical in human and rhesus monkey thalami. The area displaying specific staining of large-caliber beaded fibers coincided with nigro- and pallidothalamic afferent territories previously identified in monkeys with anterograde tracers. Accordingly, a similarly stained region in the human thalamus was considered basal ganglia territory. Except for cytoarchitecture, no specific markers differentiating between the nigro- and pallidothalamic projection zones within this territory were found. GAD65 staining in the cerebellar afferent territory reflected organization of its local circuit neuron network, distinguishing it from adjacent nuclei. Specific GAD65 staining pattern and negative calcium binding protein immunoreactivity identify the cerebellar afferent territory in humans. It is subdivided further into ventral and dorsal regions based on the cytoskeletal protein SMI31 staining pattern. The nuclear outlines revised according to the results are compared with those of Hassler (Schaltenbrand G and Bailey P [1959] Einfuhrung in die stereotaktishen Operationen mit einem Atlas des menschlichen Gehirns, vol 3. Stuttgart: Thieme) and discussed in light of the ongoing controversy regarding delineations of the motor thalamic nuclei in humans. J. Comp. Neurol. 519:2811-2837, 2011. (C) 2011 Wiley-Liss, Inc.