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bioRxiv · 10.1101/2022.08.02.502477

Brief synaptic inhibition persistently interrupts firing of fast-spiking interneurons

Chamberland, S.·Nebet, E. R.·Valero, M.·Hanani, M.·Egger, R.·Larsen, S. B.·Eyring, K. W.·Buzsaki, G.·Tsien, R. W.
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Abstract

Neurons perform input-output operations that integrate synaptic inputs with intrinsic electrical properties, operations generally constrained by the brevity of synaptic events. Here we report that sustained firing of CA1 hippocampal fast-spiking parvalbumin-expressing interneurons (PV-INs) can be persistently interrupted for up to several hundred milliseconds following brief GABAAR-mediated inhibition in vitro and in vivo. A single presynaptic neuron could interrupt PV-INs firing, occasionally with a single action potential (AP), and reliably with AP bursts. Experiments and computational modeling revealed that the persistent interruption of firing maintains neurons in a depolarized, quiescent state through a cell-autonomous mechanism. Strikingly, interrupted PV-INs are highly responsive to Schaffer collateral inputs. The persistent interruption of firing provides a disinhibitory circuit mechanism favoring spike generation in CA1 pyramidal cells. Overall, our results demonstrate that neuronal silencing can far outlast brief synaptic inhibition owing to well-tuned interplay between neurotransmitter release and postsynaptic membrane dynamics, a phenomenon impacting microcircuit function.

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Chamberland, S., Nebet, E. R., Valero, M., Hanani, M., Egger, R., Larsen, S. B., Eyring, K. W., Buzsaki, G., Tsien, R. W.. 2022-08-03. Brief synaptic inhibition persistently interrupts firing of fast-spiking interneurons. https://doi.org/10.1101/2022.08.02.502477

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