Figure 2.
Cholinergic modulation of cortical state. (a) Experimental setup for electrophysiological recordings to reveal the role of ACh in cortical desynchronization and decorrelation (Chen et al., 2015). In one experiment, the neuronal activator Channelrhodopsin (ChR2) is expressed in ChAT-expressing neurons of the basal forebrain and blue light stimulation over V1 is used to selectively release ACh in V1. In the same mice, the neuronal activity suppressor Archaerhodopsin (Arch) is expressed in somatostatin-expressing V1 neurons, and green light stimulation used to selectively suppress SOM neurons. Neuronal responses and LFPs are recorded in V1 before, during and after blue light, or simultaneous blue and green light, stimulation through the objective. (Inset) Image of Arch-GFP expression in V1. Scale bar, 50 μm. (b) LFP desynchronization during ChAT-ChR2 stimulation at t = 0 s (arrow) (top) is blocked by simultaneous SOM-Arch stimulation (green bar) (bottom). Traces were low-pass filtered (< 5 Hz). Thus, ACh release leads to desynchronization of responses, and activating SOM neurons is critical for mediating the effects of ACh. (c) Schematic illustrating the suggested circuit mechanisms underlying cholinergic modulated temporal dynamics in the superficial layers of V1. The various inhibitory neuron types (including SOM; parvalbumin-expressing, PV; vasoactive intestinal peptide-expressing, VIP; layer 1, L1) have complex inhibitory relationships with one another. PV and SOM neurons inhibit pyramidal (PYR) neurons, while SOM neurons also inhibit PV neurons. Desynchronization and decorrelation of pyramidal neuron responses following ACh release arises primarily due to the inhibitory-disinhibitory effects of PV and SOM neurons mediated through the action of ACh on SOM neurons. The effect of ACh on VIP and L1 neurons requires higher concentrations of ACh. Green ovals indicate cholinergic receptors. Red and white circles indicate inhibitory and excitatory synapses, respectively. Adapted from Chen et al. (2015).