Compressive sensing of functional connectivity maps from patterned optogenetic stimulation of neuronal ensembles

Mapping functional connectivity between neurons is an essential step toward probing the neural computa-tions mediating behavior. Accurately determining synaptic connectivity maps in populations of neurons is challenging in terms of yield, accuracy, and experimental time. Here, we developed a compressive sensing approach to reconstruct synaptic connectivity maps based on random two-photon cell-targeted optogenetic stimulation and membrane voltage readout of many putative postsynaptic neurons. Using a biophysical network model of interconnected populations of excitatory and inhibitory neurons, we characterized mapping recall and precision as a function of network observability, sparsity, number of neurons stimulated, off-target stimulation, synaptic reliability, propagation latency, and network topology. We found that mapping can be achieved with far fewer measurements than the standard pairwise sequential approach, with network sparsity and synaptic reliability serving as primary determinants of the performance. Our results suggest a rapid and efficient method to reconstruct functional connectivity of sparsely connected neuronal networks.