INTRODUCTION: Effective neural signaling requires a balance of excitatory and inhibitory neurotransmission, both of which exhibit plasticity. GABAergic inhibition can be divided into synaptic (phasic) and extrasynaptic (tonic) components, each of which exhibits plastic properties. However, the mechanisms regulating tonic inhibition and its plasticity remain poorly understood.

AIM(S): We therefore investigated heterosynaptically induced plasticity of tonic currents in distinct subtypes of somatostatin-expressing interneurons (SST+IN).

METHOD(S): We studied CA1 hippocampal slices from SST-Cre × Ai14 mice. The tonic current density was determined from the current shift following picrotoxin application, normalized to the cell membrane capacitance. Cells were filled with biocytin and imaged by confocal microscopy to classify them as OLM-like or non-OLM. Using patch-clamp recordings and pharmacology, we measured tonic currents from SST+IN and induced heterosynaptic plasticity by a 3-minute NMDA (20μM) application.

RESULTS: Data show that non-OLM cells exhibited a lower tonic current density compared to OLM-like cells (p = 0.016), which further decreased after plasticity induction with NMDA (p = 0.005). On the contrary, OLM-like cells showed no significant changes after the same protocol. Next we examined α5-GABAAR contribution in the changes of tonic current density and found a significant increase in α5 subunit contribution in tonic current density in non-OLM cells after plasticity induction (p = 0.009), whereas OLM-like cells showed no change. No differences in α5 involvement in OLM and non-OLM groups were detected under control conditions or after plasticity induction.

CONCLUSIONS: Our results indicate that OLM and non-OLM SST INs show substantially distinct tonic current densities. Moreover, only non-OLM INs show NMDA-induced plasticity which strongly depends on expression of α5 subunit containing GABAA receptors.

FINANCIAL SUPPORT: Supported by Polish National Science Centre grant OPUS 2021/43/B/NZ4/01675