Voltage imaging and optogenetics reveal behavior dependent changes in hippocampal dynamics

A technology to record membrane potential from multiple neurons, simultaneously, in behaving animals will have a transformative impact on neuroscience research(1, 2). 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(3-5). 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 and correlations in sub-threshold voltage between multiple cells. 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.