The state of somatosensory cortex during neuromodulation 3 4 5 6

34 During behavioral quiescence, such as slow wave sleep and anesthesia, the neocortex is 35 in a deactivated state characterized by the presence of slow oscillations. During arousal, slow 36 oscillations are absent and the neocortex is in an activated state that greatly impacts information 37 processing. Neuromodulators acting in neocortex are believed to mediate these state changes, but 38 the mechanisms are poorly understood. We investigated the actions of noradrenergic and 39 cholinergic activation on slow oscillations, cellular excitability and synaptic inputs in 40 thalamocortical slices of somatosensory cortex. The results show that neuromodulation abolishes 41 slow oscillations, dampens the excitability of principal cells, and rebalances excitatory and 42 inhibitory synaptic inputs in thalamocortical-recipient layers IV-III. Sensory cortex is much more 43 selective about the inputs that can drive it. The source of neuromodulation is critically important 44 in determining this selectivity. Cholinergic activation suppresses the excitatory and inhibitory 45 conductances driven by thalamocortical and intracortical inputs. Noradrenergic activation 46 suppresses the excitatory conductance driven by intracortical inputs but not by thalamocortical 47 inputs, and enhances the inhibitory conductance driven by thalamocortical inputs but not by 48 intracortical inputs. Thus, noradrenergic activation emphasizes thalamocortical (sensory) inputs 49 relative to intracortical inputs, while cholinergic activation suppresses both. 50 51 52 53 INTRODUCTION 54