Inhibitory neurons are a Central Controlling regulator in the effective cortical microconnectome

Abstract The brain is a network system in which excitatory and inhibitory neurons keep the activity balanced in the highly non-uniform connectivity pattern of the microconnectome. It is well known that the relative percentage of inhibitory neurons is much smaller than excitatory neurons. So, in general, how the inhibitory neurons can keep the balance with the surrounding excitatory neurons is an important question. We observed effective networks, reflecting causal interactions, of ~1000 neurons in cortical acute slices. Surprisingly, we found that inhibitory neurons are not only located at more central positions than excitatory neurons but also have stronger controlling ability of other neurons than excitatory neurons. Besides, we found that the precedence in centrality and controlling ability of inhibitory neurons are well observed in deep cortical layers by comparing with distribution of neurons coloured by NeuN immunostaining data. Preceding the observation, we also found that inhibitory neurons show higher firing rate than excitatory neurons, and that their firing rate also closely obey a log-normal distribution as previously known about excitatory neurons. Additionally, their connectivity strengths also obeyed a log-normal distribution. In summary, within the network interaction of huge numbers of neurons, inhibitory neurons seem to produce a central controlling system that sustains the homeostatic behavior of the brain. A similar evaluation in different life stages and in disease states etc. will not only provide deeper understandings in the homeostasis of the brain, but also will provide a selective and effective way to stimulate individual neurons to modulate neuropsychiatry or neurodegeneration disease states.