Cell type-specific distribution of GABAA receptor subtypes in the mouse dorsal striatum

The striatum is the main input nucleus of the basal ganglia, mediating motor and cognitive functions. Striatal projection neurons are GABAergic medium spiny neurons (MSN), expressing either the dopamine receptor type 1 (D-1-R MSN) and forming the direct, movement-promoting pathway, or dopamine receptor type 2 (D-2-R MSN), forming the indirect movement-suppressing pathway. Locally, activity and synchronization of MSN are modulated by several subtypes of GABAergic and cholinergic interneurons. Overall, GABAergic circuits in the striatum remain poorly characterized, and little is known about the intrastriatal connectivity of interneurons and the distribution of GABA(A) receptor (GABA(A)R) subtypes, distinguished by their subunit composition, in striatal synapses. Here, by using immunofluorescence in mouse tissue, we investigated the distribution of GABA(A)Rs containing the alpha(1), alpha(2), or alpha(3) subunit in perisomatic synapses of striatal MSN and interneurons, as well as the innervation pattern of D1R- and D2R-MSN soma and axonal initial segment (AIS) by GABAergic and cholinergic interneurons. Our results show that perisomatic GABAergic synapses of D1R- and D2R-MSN contain the GABA(A)R alpha(1) and/or alpha(2) subunits, but not the alpha(3) subunit; D2R-MSN have significantly more alpha(1)-GABA(A)Rs on their soma than D1R-MSN. Further, interneurons have few perisomatic synapses containing alpha(2)-GABA(A)Rs, whereas alpha(3)-GABA(A)Rs (along with the alpha(1)-GABA(A)Rs) are abundant in perisomatic synapses of CCK+, NPY+/SOM+, and vAChT(+) interneurons. Each MSN and interneuron population analyzed received a distinct pattern of GABAergic and cholinergic innervation, complementing this postsynaptic heterogeneity. In conclusion, intra-striatal GABAergic circuits are distinguished by cell-type specific innervation patterns, differential expression and postsynaptic targeting of GABA(A)R subtypes.