All-optical electrophysiology reveals brain-state dependent changes in hippocampal subthreshold dynamics and excitability

Adam, Y.; Kim, J. J.; Lou, S.; Zhao, Y.; Brinks, D.; Wu, H.; Mostajo-Radji, M. A.; Kheifets, S.; Parot, V.; Chettih, S.; Williams, K. J.; Farhi, S. L.; Madisen, L.; Harvey, C. D.; Zeng, H.; Arlotta, P.; Campbell, R. E.; Cohen, A. E.

doi:10.1101/281618

bioRxiv · 10.1101/281618

All-optical electrophysiology reveals brain-state dependent changes in hippocampal subthreshold dynamics and excitability

Adam, Y.·Kim, J. J.·Lou, S.·Zhao, Y.·Brinks, D.·Wu, H.·Mostajo-Radji, M. A.·Kheifets, S.·Parot, V.·Chettih, S.·Williams, K. J.·Farhi, S. L.·Madisen, L.·Harvey, C. D.·Zeng, H.·Arlotta, P.·Campbell, R. E.·Cohen, A. E.

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Abstract

A technology to record membrane potential from multiple neurons, simultaneously, in behaving animals will have a transformative impact on neuroscience research1. Parallel recordings could reveal the subthreshold potentials and intercellular correlations that underlie network behavior2. Paired stimulation and recording can further reveal the input-output properties of individual cells or networks in the context of different brain states3. Genetically encoded voltage indicators are a promising tool for these purposes, but were so far limited to single-cell recordings with marginal signal to noise ratio (SNR) in vivo4-6. We developed improved near infrared voltage indicators, high speed microscopes and targeted gene expression schemes which enabled recordings of supra- and subthreshold voltage dynamics from multiple neurons simultaneously in mouse hippocampus, in vivo. The reporters revealed sub-cellular details of back-propagating action potentials, correlations in sub-threshold voltage between multiple cells, and changes in dynamics associated with transitions from resting to locomotion. In combination with optogenetic stimulation, the reporters revealed brain state-dependent changes in neuronal excitability, reflecting the interplay of excitatory and inhibitory synaptic inputs. These tools open the possibility for detailed explorations of network dynamics in the context of behavior.

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Adam, Y., Kim, J. J., Lou, S., Zhao, Y., Brinks, D., Wu, H., Mostajo-Radji, M. A., Kheifets, S., Parot, V., Chettih, S., Williams, K. J., Farhi, S. L., Madisen, L., Harvey, C. D., Zeng, H., Arlotta, P., Campbell, R. E., Cohen, A. E.. 2018-03-13. All-optical electrophysiology reveals brain-state dependent changes in hippocampal subthreshold dynamics and excitability. https://doi.org/10.1101/281618

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