Integrated Calendar

"Sensory disconnection" – conditions when the same sensory stimulus does not reliably affect behavior or subjective experience - is a defining feature of sleep, and similar processes may occur during light anesthesia or during cognitive lapses in wakefulness. What are the changes in brain activity that mediate sensory disconnection? In a series of studies in humans and rodents, we investigate how "disconnected" states affect sensory processing. The first set of studies reveals differences in neuronal responses to identical sensory stimuli across states. We find that in humans, cognitive lapses after sleep deprivation involve attenuated and delayed single-neuron responses in MTL co-occurring with local slow/theta waves. In the auditory domain, we show in both rodents and humans that responses in sleep and light anesthesia are preserved up to A1, challenging the classic "thalamic gating" notion, but robust attenuation occurs later in high-level cortical regions. In addition, sleep affects more strongly responses that require integration over long time intervals, and responses to high-frequency content. The second set of studies investigates the underlying mechanisms, testing the potential role of locus coeruleus-noradrenaline (LC-NE) neuromodulation. In rats, we test how NE signaling affects the probability to wake up from sleep in response to sounds. We establish a new approach for selective in-vivo LC optogenetics by showing effects on spiking activity, evoked sleep-wake transitions, and pupil dilation. Combined LC and auditory stimulation synergistically increases the probability of awakenings beyond independent effects of sound and laser alone, supporting a role for LC-NE activity in mediating sensory responses. We also tested the effects of NE levels on sensory perception and sensory-evoked activity (EEG, fMRI) in awake humans. Pharmacologically manipulating NE levels in double-blind placebo-controlled experiments, we found that NE modulates sensitivity and accuracy of visual perception without significant effects on decision bias (criterion). In addition, NE increased the fidelity of late EEG visual responses, and selectively modulated BOLD fMRI responses in high-order visual cortex, suggesting that NE plays an enabling causal role in visual awareness by affecting late visual processing.