Distinct tonic inhibition and its plasticity in hippocampal OLM and non-OLM somatostatin-positive interneurons

Extrasynaptic GABA A receptors (GABA A Rs) mediating tonic inhibition are critically involved in the regulation of neuronal activity, synaptic plasticity and hippocampus-dependent learning and memory. Tonic inhibition itself was found to undergo plastic changes but the description of this plasticity in distinct subclasses of hippocampal interneurons (INs) remains incomplete. In the present study, we combined whole-cell electrophysiology with morphological reconstruction of biocytin-filled neurons to investigate plasticity of tonic GABAergic currents, induced by brief (3 min) NMDA administration, in oriens-lacunosum moleculare (OLM) and non-OLM subclasses of somatostatin-positive (SST+) INs in the hippocampal CA1 region. We found that, under control conditions, tonic current density was significantly larger in OLM than in non-OLM INs. Brief NMDA receptor activation significantly enhanced tonic current density in a subset of non-OLM SST+ INs, distinguished as the upper-median in the cumulative distribution, whereas tonic current density in OLM cells showed no plastic changes upon NMDA treatment. Since in the hippocampus, GABAergic plasticity often involves α5-containing GABA A Rs (α5-GABA A Rs), we used the selective α5-GABA A R inverse agonist L-655,708 and found that NMDA treatment increased the relative contribution of α5-GABA A Rs to tonic currents in non-OLM INs. These data altogether demonstrate that, whereas non-OLM SST+ INs show lower tonic current density than OLM cells, the former subgroup is characterized by greater susceptibility to NMDA-induced changes in tonic current density and these plastic changes are associated with an increased contribution of α5-GABA A Rs. The presented observations suggest a clear functional specialization of non-OLM and OLM SST+ INs in the regulation of hippocampal network activity.