| First Author | Borjas NC | Year | 2024 |
| Journal | J Physiol | Volume | 602 |
| Issue | 17 | Pages | 4195-4213 |
| PubMed ID | 39141819 | Mgi Jnum | J:359474 |
| Mgi Id | MGI:7788307 | Doi | 10.1113/JP286679 |
| Citation | Borjas NC, et al. (2024) Multiple layers of diversity govern the cell type specificity of GABAergic input received by mouse subicular pyramidal neurons. J Physiol 602(17):4195-4213 |
| abstractText | The 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 mu 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 omega-agatoxin IVA- but not on omega-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 mu 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. KEY 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 omega-agatoxin IVA-sensitive P/Q type voltage-gated calcium channels, whereas no major effects are observed following exposure to omega-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 mu 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. |
