Synaptic Cooperativity Regulates Persistent Network Activity in Neocortex

During behavioral quiescence, the neocortex generates spontaneous slow oscillations, which may consist of up-states and down-states. Up-states are short epochs of persistent activity that resemble the activated neocortex during arousal and cognition. Neural activity in neocortical pathways can trigger up-states, but the variables that control their occurrence are poorly understood. We used thalamocortical slices from adult mice to explore the role of thalamocortical and intracortical synaptic cooperativity (the number of coincident afferents) in driving up-states. Cooperativity was adjusted by varying the intensity of electrical or blue-light stimuli in pathways that express channelrhodopsin-2. We found that optogenetics greatly improves the study of thalamocortical pathways in slices because it produces thalamocortical responses that resemble those observed in vivo. The results indicate that more synaptic cooperativity, caused by either thalamocortical or intracortical fast AMPA-receptor excitation, leads to more robust inhibition of up-states because it drives stronger feedforward inhibition. Conversely, during strong synaptic cooperativity that suppresses up-states, blocking fast excitation, and as a result the feedforward inhibition it drives, unmasks up-states entirely mediated by slow NMDA-receptor excitation. Regardless of the pathway's origin, cooperativity mediated by fast excitation is inversely related to the ability of excitatory synaptic pathways to trigger up-states in neocortex.