The immunohistochemical distribution of the GABAA receptor α1, α2, α3, β2/3 and γ2 subunits in the human thalamus

Abstract

The GABAA receptor is the most abundant inhibitory receptor in the human brain and is assembled from a variety of different subunit subtypes which determines their pharmacology and physiology. To determine which GABAA receptor subunit proteins are found in the human thalamus we investigated the distribution of five major GABAA receptor subunits α1, α2, α3, β2,3 and γ2 using immunohistochemical techniques. The α1-, β2,3- and γ2- subunits which combine to form a benzodiazepine sensitive GABAA receptor showed the most intense levels of staining and were the most common subunits found throughout the human thalamus especially in the ventral and posterior nuclear groups. The next most intense staining was for the α3-subunit followed by the α2-subunit. The intralaminar nuclear group, the mediodorsal nucleus and the thalamic reticular nucleus contained α1-, β2,3- and γ2- subunits staining as well as the highest levels of the α2- and α3- subunits. The sensory dorsal lateral geniculate nucleus contained very high levels of α1- and β2,3- and γ2-subunits. The highest densities of GABAA receptors found throughout the thalamus which contained the subunits α1, β2,3, and γ2 included nuclei which are especially involved in the control or the modulation of the cortico-basal ganglia-thalamo-cortical motor circuits and are thus important in disorders such as Huntington's disease where the GABAergic projections of the basal ganglia are compromised. In addition the majority of receptors in the thalamic reticular nucleus contain α3 and γ2 subunits whilst the intralaminar nuclei contain high levels of α2 and α3 subunits.