Expression of the GABA(A) receptor gamma4-subunit gene in discrete nuclei within the zebra finch song system.

The acquisition, production and maintenance of song by oscine birds is a form of audition-dependent learning that, in many ways, resembles the process by which humans learn to speak. In songbirds, the generation of structured song is determined by the activity of two interconnected neuronal pathways (the anterior forebrain pathway and the vocal motor pathway), each of which contains a number of discrete nuclei that together form the song system. It is becoming increasingly evident that inhibitory GABAergic mechanisms are indispensable in counterbalancing the excitatory actions of glutamate and, thus, likely shape the neuronal firing patterns of neurons within this network. Furthermore, there is compelling evidence for the involvement of GABA(A) receptors, although the molecular composition of these has, to date, remained elusive. Here we describe the isolation of a complementary DNA for the zebra finch GABA(A) receptor gamma4 subunit, and map the expression pattern of the corresponding gene within the zebra finch (Taeniopygia guttata) brain. Our findings show, remarkably, that the gamma4-subunit transcript is highly enriched in the major nuclei of the song system, including the lateral magnocellular nucleus of the anterior nidopallium (LMAN), the medial magnocellular nucleus of the anterior nidopallium (MMAN), Area X, the robust nucleus of the arcopallium (RA) and the HVC (used as the proper name), as well as Field L, which innervates the area surrounding HVC. In summary, we have demonstrated the presence of the mRNA for the gamma4 subunit of the GABA(A) receptor, the major inhibitory receptor in brain, in most of the nuclei of the two neural circuits that mediate song production in the zebra finch. This not only marks the beginning of the characterization of the GABA(A) receptor subtype(s) that mediates the actions of GABA in the song system but it also provides a robust molecular marker with which to distinguish song system-specific brain structures.