Theory of Neuronal Perturbome: Linking Connectivity to Coding via Perturbations

To unravel the functional properties of the brain, we need to untangle how neurons interact with each other and coordinate in large-scale recurrent networks. One way to address this question is to measure the functional influence of individual neurons on each other by perturbing them in vivo. Application of such single-neuron perturbations in mouse visual cortex has recently revealed feature-specific suppression between excitatory neurons, despite the presence of highly specific excitatory connectivity, which was deemed to underlie feature-specific amplification. Here, we studied which connectivity profiles are consistent with these seemingly contradictory observations, by modelling the effect of single-neuron perturbations in large-scale neuronal networks. Our numerical simulations and mathematical analysis revealed that, contrary to the prima facie assumption, neither inhibition-dominance nor broad inhibition alone were sufficient to explain the experimental findings; instead, strong and functionally specific excitatory-inhibitory connectivity was necessary, consistent with recent findings in the primary visual cortex of rodents. Such networks had a higher capacity to encode and decode natural images in turn, which was accompanied by the emergence of response gain nonlinearities at the population level. Our study provides a general computational framework to investigate how single-neuron perturbations are linked to cortical connectivity and sensory coding, and paves the road to map the perturbome of neuronal networks in future studies.