A deep learning framework for inference of single-trial neural population dynamics from calcium imaging with subframe...

In many areas of the brain, neural populations act as a coordinated network whose state is tied to behavior on a millisecond timescale. Two-photon (2p) calcium imaging is a powerful tool to probe such network-scale phenomena. However, estimating the network state and dynamics from 2p measurements has proven challenging because of noise, inherent nonlinearities and limitations on temporal resolution. Here we describe Recurrent Autoencoder for Discovering Imaged Calcium Latents (RADICaL), a deep learning method to overcome these limitations at the population level. RADICaL extends methods that exploit dynamics in spiking activity for application to deconvolved calcium signals, whose statistics and temporal dynamics are quite distinct from electrophysiologically recorded spikes. It incorporates a new network training strategy that capitalizes on the timing of 2p sampling to recover network dynamics with high temporal precision. In synthetic tests, RADICaL infers the network state more accurately than previous methods, particularly for high-frequency components. In 2p recordings from sensorimotor areas in mice performing a forelimb reach task, RADICaL infers network state with close correspondence to single-trial variations in behavior and maintains high-quality inference even when neuronal populations are substantially reduced.