, 2009). These studies suggest that while selective attention can preferentially enhance the responses to the attended stimuli, a general increase

in vigilance may in fact reduce the overall response in order to accentuate representation of the relevant stimulus (Atiani et al., 2009). In contrast to the findings above, a drug discovery study in mouse visual cortex showed that the neuronal responses to drifting grating stimuli are much higher when the mouse was behaviorally active (running) than inactive (standing still) (Niell and Stryker, 2010). One factor that may contribute to the discrepancy among these experiments is the use of transient (e.g., a brief sound or tactile stimulus) versus sustained (e.g., drifting gratings) sensory stimuli, which evoke different degrees of neuronal adaptation (Harris selleck and Thiele, 2011), as strong adaptation is observed primarily in behaviorally inactive states (Castro-Alamancos, 2004a). More importantly, the modulation of sensory responses by different behaviors—selective attention to a single stimulus, nonselective increase in vigilance, and general behavioral arousal (e.g., running)—may be mediated by different mechanisms, involving partially overlapping but nonidentical sets of neuromodulatory inputs. Testing this hypothesis will require simultaneous measurement of activity of both the neuromodulatory systems and the sensory neurons under the

different behavioral paradigms. Optogenetic manipulation of each neuromodulatory system (Figures 4C and 4D) will also reveal its impact on the activity of sensory neurons within each behavioral context. While it is well accepted that the aroused, attentive states are favorable for sensory processing, what are the functions of the synchronized brain states? In particular, why is sleep so universal in the animal isothipendyl kingdom (Cirelli and Tononi, 2008), given that the loss of responsiveness to environmental stimuli makes the animal more vulnerable to predator attacks?

The importance of sleep can be appreciated from the severe effects of sleep deprivation on cognitive functions and general health. Prolonged total sleep deprivation is known to be lethal in flies (Shaw et al., 2002) and rats (Rechtschaffen and Bergmann, 2002), although some of the harmful effects may be attributable to the stress induced by the experimental methods of deprivation. Specifically, one function of sleep may be energy conservation or brain recuperation (Siegel, 2005). A recent study showed that the ATP concentration surges in the first few hours of sleep, and the level of surge is correlated with the EEG delta activity during NREM sleep (Dworak et al., 2010). However, the cause for this energy surge may not be a simple reduction of neuronal activity. We know that during NREM sleep many neurons remain highly active, and the difference from the awake state resides more in the spatiotemporal pattern than in the overall level of neural activity.