Variable colocalisation of GABAA receptor subunits and glycine receptors on neurons in the human hypoglossal nucleus

The hypoglossal nucleus, the nucleus of the twelfth cranial nerve, is located dorsally in the midline of the medulla oblongata. The hypoglossal nucleus contains lower motor neurons which innervate the tongue muscles that control tongue movements involved in speech production, swallowing, mastication and associated respiratory movements. GABA(A) and glycine receptors are heteropentameric ionotropic receptors that facilitate fast-response, inhibitory neurotransmission in the mammalian brain and spinal cord. We investigated the immunohistochemical distribution of the GABA(A) receptor alpha(1), alpha(2), beta(2,3) subunits and glycine receptors as well as their relationship to the vesicular GABA transporter (VGAT) in the human hypoglossal nucleus at the light and confocal laser scanning microscope levels. The results showed that all of the GABA(A) receptor subunits as well as glycine receptor display punctate labelling indicative of synapses on the soma and dendritic membranes of large neurons within the hypoglossal nucleus. On average, approximately 50% of glycine receptors were co localised with GABA(A) receptor alpha(1) subunits. Also on average GABA(A) alpha(2) and beta(2,3) subunits were colocalised with approximately 30% of glycine receptor subunits. VGAT positive terminals were associated with both GABA(A) and glycine receptor types. Both glycinergic and GABAergic positive puncta were found adjacent to VGAT terminallike staining. These results suggest that inhibition of human hypoglossal motor neurons occurs not only through complex interaction of separated GABA(A)R and glycine receptor regions, but also through synapses containing both inhibitory receptor types co-existing at the same synaptic sites.