Interrogation of inter-layer neuronal connectivity via cross-region all-optical physiology with high temporal resolution

Abstract

AbstractThe interrogation of functional neural circuits is crucial for uncovering how the brain works during diverse behaviours. Multi-area neurophysiological measurement systems with high temporal resolution are indispensable, especially for dissecting inter-region functional connectivity. Here, we develop a cross-region all-optical physiology system (CRAOP) that enables the simultaneous recording and manipulation of single-neuron activities in multiple brain areas. Based on spatiotemporal multiplexing, our system enables all-optical analysis in the cortex and hippocampus with a high frame rate and minimal time delay in inter-layer imaging and photostimulation. Combined with behavioural experiments, CRAOP provides all-optical evidence linking behavioural responses to neuronal connectivity in the primary visual cortex (V1) in live mice. Furthermore, we demonstrate that CRAOP can perturb the activity response of interregional cortical neurons to sensory stimuli according to their functional signatures. Overall, CRAOP provides an optical approach for mapping interlayer connectivity at the single-neuron level and for modifying neuronal responses in behaving animals.