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Equalizing excitation–inhibition ratios across visual cortical neurons

2014; Nature Portfolio; Volume: 511; Issue: 7511 Linguagem: Inglês

10.1038/nature13321

1476-4687

Mingshan Xue, Bassam V. Atallah, Massimo Scanziani,

Photoreceptor and optogenetics research

Different amounts of excitation received by different pyramidal cells of primary visual cortex are matched by proportional amounts of inhibition. The balance between synaptic excitation and inhibition in the mammalian sensory cortex — known as the E/I ratio — is an important influence on both sensory processing and cognitive function. The mechanisms that establish and maintain the E/I ratio are still poorly understood. It is not clear whether each cortical neuron has the ability of individually regulating its own E/I ratio or if the E/I ratio is equalized across the pyramidal cell population. In a study of mouse primary visual cortex, Massimo Scanziani and colleagues show that E/I ratios are remarkably similar across different pyramidal cells despite large variations in the amplitudes of synaptic excitation and inhibition. This is achieved through matched inhibition mediated by parvalbumin-expressing but not by somatostatin-expressing interneurons. The relationship between synaptic excitation and inhibition (E/I ratio), two opposing forces in the mammalian cerebral cortex, affects many cortical functions such as feature selectivity and gain1,2. Individual pyramidal cells show stable E/I ratios in time despite fluctuating cortical activity levels. This is because when excitation increases, inhibition increases proportionally through the increased recruitment of inhibitory neurons, a phenomenon referred to as excitation–inhibition balance3,4,5,6,7,8,9. However, little is known about the distribution of E/I ratios across pyramidal cells. Through their highly divergent axons, inhibitory neurons indiscriminately contact most neighbouring pyramidal cells10,11. Is inhibition homogeneously distributed12 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 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 but not somatostatin-expressing inhibitory cells and results from the independent adjustment of synapses originating from individual parvalbumin-expressing cells 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 the cortex’s two opposing forces is stabilized not only in time but also in space.