Figure 4.

Circuit effects of rapid and slow modulation of cortical state. A. Recent investigations have revealed that disinhibition may be a significant mechanism modulating the responsiveness of cortical pyramidal cells [55–57,82]. The proposed microcircuit consists of VIP-containing interneurons inhibiting SOM and PV interneurons, resulting in enhanced responsiveness of postsynaptic pyramidal cells. VIP interneurons are modulated by several ionotropic pathways (nicotinic, 5HT3A, glu), which may allow for the rapid modulation of these neurons. B. Multiplicative gain modulation is a major mechanism by which the input-output relationship of cortical neurons may be modulated. Multiplicative gain modulation can be achieved by changes in the mean membrane potential in the presence of membrane potential variance [61]. C. Suppression of ongoing fluctuations in network activity can result in a significant increase in the reliability of cortical responses to sensory stimuli. Illustrated here are the local field potentials evoked in S1 in response to whisker stimulation either with (M1 stim) or without (control) optogenetic stimulation of feedback pathways from M1 to S1. D. The activation of cortical networks may result in selective propagation of neuronal activity by enhancing synchronization, which allows temporal summation of synaptic responses to bring the postsynaptic neuron to firing threshold. B is adapted from [43]; C is from [8]; D is from [75].