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bioRxiv · 10.64898/2026.10.05.756595

Large-scale all-optical electrophysiology links excitability and connectivity to circuit dynamics in vivo

Qi, Y.·Parot, V. J.·Wu, X.·Plutkis, S. E.·Lavis, L. D.·Cohen, A. E.
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Abstract

To understand neural computations, one would like to relate circuit dynamics to neuronal intrinsic excitability and connectivity. We developed tools for large-scale all-optical electrophysiology and applied them to approximately 300 layer 1 interneurons per mouse in vivo. Across two mice, targeted stimulation and voltage imaging identified 1,469 inhibitory and 5,752 directed electrical connections among 14,312 tested pairs. Presynaptic identity was more strongly associated with inhibitory post-synaptic potential (IPSP) amplitude, whereas postsynaptic identity was more strongly associated with IPSP decay time. Gap junctional and synaptic interactions had distinct spatiotemporal kernels, with corresponding signatures in spontaneous activity. Excitability measured under optogenetic stimulus predicted spiking responses to subthreshold voltage, depolarization rate, and spike history during spontaneous firing. Genetic subtypes also showed different behavioral-state-dependent voltage-to-spike relationships despite similar population-average subthreshold voltages. These measurements link cellular properties and pairwise interactions to spontaneous circuit dynamics, establishing an approach for functional circuit mapping in vivo.

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Qi, Y., Parot, V. J., Wu, X., Plutkis, S. E., Lavis, L. D., Cohen, A. E.. 2026-10-12. Large-scale all-optical electrophysiology links excitability and connectivity to circuit dynamics in vivo. https://doi.org/10.64898/2026.10.05.756595

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