Differential effects of cholinergic and noradrenergic neuromodulation on spontaneous cortical network dynamics

• Application of CCh or NE increased spontaneous activity in acute cortical slices.
• CCh mediated increase was blocked by muscarinic M1 receptor antagonist.
• NE induced a plasticity-mediated, outlasting increase in spontaneous activity.
• The outlasting effect of NE was mediated by deep layers of cortex.
• Both agents increased the spatiotemporal complexity of activity.

Cholinergic and noradrenergic neuromodulation play a key role in determining overall behavioral state by shaping the underlying cortical network dynamics. The effects of these systems on synaptic and intrinsic cellular targets are quite diverse and a comprehensive understanding of how these neuromodulators regulate (spontaneous) cortical network activity has remained elusive. Here, we used multielectrode electrophysiology in vitro to investigate the effect of these neuromodulators on spontaneous network dynamics in acute slices of mouse visual cortex. We found that application of Carbachol (CCh) and Norepinephrine (NE) both enhanced the spontaneous network dynamics by increasing (1) the activity levels, (2) the temporal complexity of the network activity, and (3) the spatial complexity by decorrelating the network activity over a wide range of neuromodulator concentrations (1 μM, 10 μM, 50 μM, and 100 μM). Interestingly, we found that cholinergic neuromodulation was limited to the presence of CCh in the bath whereas the effects of NE, in particular for higher concentrations, induced plasticity that caused outlasting effects most prominently in the deep cortical layers. Together, these results provide a comprehensive network-level understanding of the similarities and differences of cholinergic and noradrenergic modulation of spontaneous network dynamics.