All-optical electrophysiology reveals brain-state dependent changes in hippocampal subthreshold dynamics and excitability
Jeong J Kim,
Mohammed A. Mostajo-Radji,
Katherine J Williams,
Samouil L Farhi,
Christopher D. Harvey,
Robert E. Campbell,
Adam E. Cohen
Posted 13 Mar 2018
bioRxiv DOI: 10.1101/281618 (published DOI: 10.1038/s41586-019-1166-7)
Posted 13 Mar 2018
A technology to record membrane potential from multiple neurons, simultaneously, in behaving animals will have a transformative impact on neuroscience research. Parallel recordings could reveal the subthreshold potentials and intercellular correlations that underlie network behavior. Paired stimulation and recording can further reveal the input-output properties of individual cells or networks in the context of different brain states. 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 vivo. 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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