Serotonergic blockers did not prevent the disappearance of slow waves upon waking (Figures 5E, blue; Figure S5C), validating a role for norepinephrine in switching cortical dynamics. We conclude that arousal dramatically transforms the temporal pattern of spontaneous synaptic inputs in cortical networks. Local

recurrent networks appear able to generate a relatively constant level of background synaptic input. Our study demonstrates that wakeful patterns of synaptic input can occur independent of primary and secondary sensory thalamic nuclei, contrary to the idea that global brain states PF-06463922 in vivo influence local cortical networks via thalamic afferents (Hirata and Castro-Alamancos, 2010 and Steriade et al., 1993b). Cholinergic selleck products modulation was also unnecessary to achieve awake cortical dynamics. We found that ACh more noticeably impacts sensory-evoked responses, a capacity that may subserve attentional focusing on selected stimuli. In contrast, the powerful influence of arousal on cortical dynamics required norepinephrine. Electrical stimulation

of nonspecific intralaminar thalamic nuclei, which diffusely project across cortex, initially implicated them in arousal (reviewed in Van der Werf et al., 2002). Lesions of intralaminar nuclei do not, however, alter EEG patterns (Buzsaki et al., 1988 and Vanderwolf and Stewart, 1988). Indeed, we found that wakefulness still profoundly affected cortical dynamics after our thalamic lesions, which severed connections between cortex and the central lateral intralaminar nucleus, the most investigated for a role in arousal. Our results do not rule out possible contributions of the central medial nucleus, parafascicular complex, or rhomboid nucleus. These, much however, seem unlikely given that sparse axons

from these intralaminar nuclei avoid L4 (Van der Werf et al., 2002), where we investigated mechanism. Moreover, these projections would have to act through L2/3-L4 and L5/6-L4 synapses, which are also anatomically sparse and, in those rare instances when observed, substantially (∼2–6 fold) weaker than L4-L4 synapses (Gottlieb and Keller, 1997, Lefort et al., 2009 and Schubert et al., 2003). A more likely explanation for the switch in cortical dynamics, therefore, is that NE directly modulates synapses among L4 neurons. Electrical stimulation of cholinergic nuclei is sufficient to produce awake-like cortical activity in anesthetized animals (Goard and Dan, 2009, Metherate et al., 1992 and Steriade et al., 1993a). We found, however, that cholinergic modulation is unnecessary to achieve wakeful cortical dynamics. Our experiments do not rule out possible behavioral contexts in which natural ACh release could alter dynamics.