Immunohistochemical localization of GABAB receptors in the rat central nervous system

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Abstract
The recent cloning of two γ-aminobutyric acidB (GABAB) receptor isoforms (GABABR1a/b), which are probably splice variants of the same gene transcript, allowed us to develop an antiserum that recognized the receptors in fixed tissue and to map their distribution in the rat central nervous system (CNS). We also investigated whether GABABR1 colocalizes with glutamic acid decarboxylase (GAD), a marker of GABAergic cell bodies and terminals. Although GABABR1-like immunoreactivity (GABABR1-LI) was distributed throughout the CNS, several distinct distribution patterns emerged: (1) all monoaminergic brainstem cell groups appeared to contain very high levels of GABABR1, (2) a very high intensity of GABABR1-LI was observed in the majority of the cholinergic regions in the CNS, with exception of motoneurons of the third through sixth cranial nerve nuclei, and (3) a low density of the receptor was observed in most of the nuclei that contain cell bodies of GABAergic projection neurons. The highest GABABR1 labeling was observed in the thalamus, interpeduncular nucleus and medial habenula. Cell bodies were labeled throughout the neuroaxis. We also observed dense neuropil labeling in many regions, suggesting that this receptor is localized in dendrites and/or axon terminals. However, in immunofluorescent double-labeling experiments for GABABR1 and GAD, we never observed GABABR1-LI in GAD-positive axon terminals; this result suggests that the GABABR1 may not function as an autoreceptor. Double labeling was observed in the cell bodies of Purkinje neurons and in some interneurons. In general, the immunohistochemical localization of the GABABR1 correlates well with physiologic and autoradiographic data on the distribution of GABAB receptors, but some critical differences were noted. Thus, it is likely that additional GABAB receptor subtypes remain to be identified. J. Comp. Neurol. 405:299–321, 1999.