Internally generated activity may

reflect arousal, attention, anticipation of reward, or other nonsensory signals related to the behavioral state of an organism. How do global brain states alter activity in local cortical networks, and what are the cellular mechanisms responsible for such changes in cortical processing? The most overtly observable brain states are perhaps found in the sleep-wake cycle, with substantial behavioral and perceptual differences between sleeping, drowsy, and alert states. Brain potentials (electroencephalogram; EEG) exhibit prominent slow-wave oscillations (<2 Hz) during natural deep sleep and under anesthesia but not during wakefulness (Steriade et al., 1993b). EEG slow waves derive from relatively click here synchronous discharges of large populations of neurons (Steriade et al., 2001). These discharges are separated by periods of synaptic quiescence, during which virtually all of the thousands of synapses contacting a neuron are inactive. Intracellular Palbociclib purchase recording affords a unique view of network activity, reporting the activity

of these numerous connected cells. The resulting membrane potential (Vm) modulates the impact of subsequent synaptic inputs. In anesthetized animals, Vm at the time of a sensory stimulus strongly influences the amplitude of postsynaptic potentials as well as the number and relative timing of action potentials evoked (Petersen et al., 2003 and Sachdev et al., 2004). In slice, synapses more or less effectively transmit sensory information depending on cortical Vm (Rigas and Castro-Alamancos, 2009 and Watson et al., 2008). Therefore, instantaneous Vm may influence anatomically connected cells’ functional connectivity (Haider and McCormick, 2009) perhaps subserving high-level functions. The temporal patterns of synaptic inputs (network dynamics) during wakefulness are less clear. Heroic sharps recordings initially provided several examples of neurons in multimodal association areas of cat neocortex that exhibit pronounced slow-wave fluctuations

during natural sleep but not wakefulness (Steriade et al., 2001). oxyclozanide Wakefulness was characterized instead by persistent depolarization and high action potential discharge rates. In contrast, a later whole-cell study described low-frequency fluctuations in layer 2/3 pyramidal neurons in rodent primary somatosensory cortex during “quiet wakefulness” (Petersen et al., 2003; see also Poulet and Petersen, 2008), though these have yet to be directly compared to those during sleep/anesthesia. The earlier cat studies observed no slow-wave synaptic patterns during wakefulness, but cell types were unidentified. How arousal affects individual neurons of different types is unresolved. The mechanism by which arousal may alter cortical dynamics is also unclear. Electrical stimulation of the brainstem cholinergic center innervating the thalamus enhances thalamic discharge and tonically depolarizes cortical neurons (Steriade et al.