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Global enhancement of cortical excitability following coactivation of large neuronal populations

Significance Propagating cortical waves that evoke correlated firing of large neuronal populations may cause long-term modification of neural circuits in the brain. Using optogenetic stimulation, we found that repetitive coactivation of large populations of mouse cortical neurons led to enhanced excitability of cortical neurons in both coactivated areas and distant areas that were not coactivated, including those in the contralateral cortices. This global enhancement of neuronal excitability caused by local neuronal stimulation was accompanied by the potentiation of excitatory synaptic transmission, suggesting activity-dependent synaptic plasticity. The corticothalamocortical circuit could contribute to the propagation of this enhancement effect. These results show that the repetitive correlated excitation of large neuronal populations could lead to global enhancement of neuronal excitability. Correlated activation of cortical neurons often occurs in the brain and repetitive correlated neuronal firing could cause long-term modifications of synaptic efficacy and intrinsic excitability. We found that repetitive optogenetic activation of neuronal populations in the mouse cortex caused enhancement of optogenetically evoked firing of local coactivated neurons as well as distant cortical neurons in both ipsilateral and contralateral hemispheres. This global enhancement of evoked responses required coactivation of a sufficiently large population of neurons either within one cortical area or distributed in several areas. Enhancement of neuronal firing was saturable after repeated episodes of coactivation, diminished by inhibition of N-methyl-d-aspartic acid receptors, and accompanied by elevated excitatory postsynaptic potentials, all consistent with activity-induced synaptic potentiation. Chemogenetic inhibition of neuronal activity of the thalamus decreased the enhancement effect, suggesting thalamic involvement. Thus, correlated excitation of large neuronal populations leads to global enhancement of neuronal excitability.