Multiple layers of diversity govern the cell type specificity of GABAergic input received by mouse subicular pyramidal neurons

Abstract

AbstractThe subiculum is a key region of the brain involved in the initiation of pathological activity in temporal lobe epilepsy, and local GABAergic inhibition is essential to prevent subicular‐originated epileptiform discharges. Subicular pyramidal cells may be easily distinguished into two classes based on their different firing patterns. Here, we have compared the strength of the GABAa receptor‐mediated inhibitory postsynaptic currents received by regular‐ vs. burst‐firing subicular neurons and their dynamic modulation by the activation of μ opioid receptors. We have taken advantage of the sequential re‐patching of the same cell to initially classify pyramidal neurons according to their firing patters, and then to measure GABAergic events triggered by the optogenetic stimulation of parvalbumin‐ and somatostatin‐expressing interneurons. Activation of parvalbumin‐expressing cells generated larger responses in postsynaptic burst‐firing neurons whereas the opposite was observed for currents evoked by the stimulation of somatostatin‐expressing interneurons. In all cases, events depended critically on ω‐agatoxin IVA‐ but not on ω‐conotoxin GVIA‐sensitive calcium channels. Optogenetic GABAergic input originating from both parvalbumin‐ and somatostatin‐expressing cells was reduced in amplitude following the exposure to a μ opioid receptor agonist. The kinetics of this pharmacological sensitivity was different in regular‐ vs. burst‐firing neurons, but only when responses were evoked by the activation of parvalbumin‐expressing neurons, whereas no differences were observed when somatostatin‐expressing cells were stimulated. In conclusion, our results show that a high degree of complexity regulates the organizing principles of subicular GABAergic inhibition, with the interaction of pre‐ and postsynaptic diversity at multiple levels. imageKey points Optogenetic stimulation of parvalbumin‐ and somatostatin‐expressing interneurons (PVs and SOMs) triggers inhibitory postsynaptic currents (IPSCs) in both regular‐ and burst‐firing (RFs and BFs) subicular pyramidal cells. The amplitude of optogenetically evoked IPSCs from PVs (PV‐opto IPSCs) is larger in BFs whereas IPSCs generated by the light activation of SOMs (SOM‐opto IPSCs) are larger in RFs. Both PV‐ and SOM‐opto IPSCs critically depend on ω‐agatoxin IVA‐sensitive P/Q type voltage‐gated calcium channels, whereas no major effects are observed following exposure to ω‐conotoxin GVIA, suggesting no significant involvement of N‐type channels. The amplitude of both PV‐ and SOM‐opto IPSCs is reduced by the probable pharmacological activation of presynaptic μ opioid receptors, with a faster kinetics of the effect observed in PV‐opto IPSCs from RFs vs. BFs, but not in SOM‐opto IPSCs. These results help us understand the complex interactions between different layers of diversity regulating GABAergic input onto subicular microcircuits.