Activation of axon initial segmental GABAA receptors inhibits action potential generation in neocortical GABAergic interneurons

Abstract Ionotropic GABA A receptors expressing at the axon initial segment (AIS) of glutamatergic pyramidal cell (PC) in the cortex plays critical roles in regulating action potential generation. However, it remains unclear whether these receptors also express at the AIS of cortical GABAergic interneurons. In mouse prefrontal cortical slices, we performed experiments at the soma and AIS of the two most abundant GABAergic interneurons: parvalbumin (PV) and somatostatin (SST) positive neurons. Local application of GABA at the perisomatic axonal regions could evoke picrotoxin-sensitive currents with a reversal potential near the Cl − equilibrium potential. Puffing agonists to outside-out patches excised from AIS confirmed the expression of GABA A receptors. Further pharmacological experiments revealed that GABA A receptors in AIS of PV neurons contain α1 subunits, different from those containing α2/3 in AIS and α4 in axon trunk of layer-5 PCs. Cell-attached recording at the soma of PV and SST neurons revealed that the activation of AIS GABA A receptors inhibits the action potential generation induced by synaptic stimulation. Together, our results demonstrate that the AIS of PV and SST neurons express GABA A receptors with distinct subunit composition, which exert an inhibitory effect on neuronal excitability in these inhibitory interneurons.