GABAρ selective antagonist TPMPA partially inhibits GABA-mediated currents recorded from neurones and astrocytes in mouse striatum.

Abstract The neostriatum plays a central role in motor coordination where nerve cells operate neuronal inhibition through GABAergic transmission. The neostriatum expresses a wide range of GABA-A subunits, including GABAρ1 and ρ2 which are restricted to a fraction of GABAergic interneurons and astrocytes. Spontaneous postsynaptic currents (sPSCs) evoked by 4-aminopyridine (4-AP) were recorded from neurones of the dorsal neostriatum, and their frequency was reduced > 50% by the selective GABAρ antagonist (1,2,5,6-Tetrahydropyridine-4-yl) methylphosphinic acid (TPMPA). Additionally, we recorded GABA evoked currents from astrocytes in vitro and in situ . Astrocytes in vitro showed modulation by pentobarbital and desensitization upon consecutive applications of GABA. However, modulation by pentobarbital was absent and no significant desensitization was detected from astrocytes in situ . Moreover, TPMPA-sensitive GABA-currents that were insensitive to bicuculline were also recorded from astrocytes in situ , consistent with our previous study where GABAρ expression was demonstrated. Finally, we assessed the mRNA expression of GABAρ3, through different stages of postnatal development; double immunofluorescence disclosed GABAρ3 expression in calretinin-positive interneurons as well as in astrocytes (>70%). These results add new information about the participation of GABAρ subunits in neostriatal interneurons and astrocytes.