Activation of parvalbumin-expressing cells generates larger inhibitory currents in burst-firing subicular neurons.
Subicular pyramidal cells can be classified into regular-firing and burst-firing based on their firing patterns.
Optogenetic stimulation of parvalbumin-expressing interneurons produces larger inhibitory postsynaptic currents in burst-firing neurons, while stimulation of somatostatin-expressing interneurons results in larger currents in regular-firing neurons.
Inhibitory postsynaptic currents from both types of interneurons critically depend on ω-agatoxin IVA-sensitive calcium channels.
Exposure to a μ opioid receptor agonist reduces the amplitude of inhibitory postsynaptic currents from both parvalbumin- and somatostatin-expressing cells.
The kinetics of the reduction in inhibitory currents differs between regular- and burst-firing neurons when activated by parvalbumin-expressing interneurons, but not when activated by somatostatin-expressing interneurons.
Simplified
The subiculum is a key region of the brain involved in the initiation of pathological activity in temporal lobe epilepsy, and local 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. 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 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.
Key numbers
2.4 nA
Amplitude of PV-opto IPSCs in BFs
Mean amplitude in burst-firing pyramidal cells from 42 mice.
1.7 nA
Amplitude of SOM-opto IPSCs in RFs
Mean amplitude in regular-firing pyramidal cells from 38 mice.
51.9%
Reduction of PV-opto IPSCs by DAMGO in RFs
Percentage of baseline in regular-firing neurons with 19 cells.
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