Equalizing Excitation-Inhibition Ratios across Visual Cortical Neurons

The relationship between synaptic excitation and inhibition (E/I ratio), two opposing forces in the mammalian cerebral cortex, affects many cortical functions like feature selectivity and gain(1,2). Individual pyramidal cells show stable E/I ratios in time despite fluctuating cortical activity levels because when excitation increases, inhibition increases proportionally through the increased recruitment of inhibitory neurons, a phenomenon referred to as excitation-inhibition balance(3–9). However, little is known about the distribution of E/I ratios across pyramidal cells. Through their highly divergent axons inhibitory neurons indiscriminately contact most neighboring pyramidal cells(10,11). Is inhibition homogeneously distributed or is it individually matched to the different amounts of excitation received by distinct pyramidal cells? Here we discover that pyramidal cells in layer 2/3 of mouse primary visual cortex (V1) each receive inhibition in a similar proportion to their excitation. As a consequence E/I ratios are equalized across pyramidal cells. This matched inhibition is mediated by parvalbumin-expressing (PV) but not somatostatin-expressing (SOM) inhibitory neurons and results from the independent adjustment of synapses originating from the same PV cell but targeting different pyramidal cells. Furthermore, this match is activity-dependent as it is disrupted by perturbing pyramidal cell activity. Thus, the equalization of E/I ratios across pyramidal cells reveals an unexpected degree of order in the spatial distribution of synaptic strengths and indicates that the relationship between cortex’s two opposing forces is stabilized not only in time but also in space.