Summary Sleep is traditionally constituted of two global behavioral states, NREM and REM, characterized by quiescence and reduced responsiveness to sensory stimuli [1]. NREM sleep is distinguished by slow waves and spindles throughout the cerebral cortex, REM sleep by an ‘activated’, low-voltage fast EEG paradoxically similar to that of wake, accompanied by rapid eye movements and muscle atonia. However, recent evidence has shown that cortical activity patterns during wake and NREM sleep are not as global as previously thought. Local slow waves can appear in various cortical regions in both awake humans [2] and rodents [3-5]. Intracranial recordings in humans [6] and rodents [4, 7] have shown that NREM sleep slow waves most often involve only a subset of brain regions that varies from wave to wave rather than occurring near-synchronously across all cortical areas. Moreover, some cortical areas can transiently ‘wake up’ [8] in an otherwise sleeping brain. Yet, until now, cortical activity during REM sleep was thought to be homogenously wake-like. We show here, using local laminar recordings in freely moving mice, that slow waves occur regularly during REM sleep, but only in primary sensory and motor areas, and mostly in layer 4, the main target of relay thalamic inputs, and in layer 3. This finding may help explain why during REM sleep we remain disconnected from the environment even though the bulk of the cortex shows wakelike, paradoxical activation.

During non-rapid eye-movement (NREM) sleep, cortical and thalamic neurons oscillate every second or so between ON periods, characterized by membrane depolarization and wake-like tonic firing, and OFF periods, characterized by membrane hyperpolarization and neuronal silence. Cortical slow waves, the hallmark of NREM sleep, reflect near-synchronous OFF periods in cortical neurons. However, the mechanisms triggering such OFF periods are unclear, as there is little evidence for somatic inhibition. We studied cortical inhibitory interneurons that express somatostatin (SOM), because ∼70% of them are Martinotti cells that target diffusely layer I and can block excitatory transmission presynaptically, at glutamatergic terminals, and postsynaptically, at apical dendrites, without inhibiting the soma. In freely moving male mice, we show that SOM+ cells can fire immediately before slow waves and their optogenetic stimulation during ON periods of NREM sleep triggers long OFF periods. Next, we show that chemogenetic activation of SOM+ cells increases slow-wave activity (SWA), slope of individual slow waves, and NREM sleep duration; whereas their chemogenetic inhibition decreases SWA and slow-wave incidence without changing time spent in NREM sleep. By contrast, activation of parvalbumin+ (PV+) cells, the most numerous population of cortical inhibitory neurons, greatly decreases SWA and cortical firing, triggers short OFF periods in NREM sleep, and increases NREM sleep duration. Thus SOM+ cells, but not PV+ cells, are involved in the generation of sleep slow waves. Whether Martinotti cells are solely responsible for this effect, or are complemented by other classes of inhibitory neurons, remains to be investigated. Cortical slow waves are a defining feature of non-rapid eye-movement (NREM) sleep and are thought to be important for many of its restorative benefits. Yet, the mechanism by which cortical neurons abruptly and synchronously cease firing, the neuronal basis of the slow wave, remains unknown. Using chemogenetic and optogenetic approaches, we provide the first evidence that links a specific class of inhibitory interneurons-somatostatin-positive cells-to the generation of slow waves during NREM sleep in freely moving mice.

During non-rapid eye movement (NREM) sleep, cortical neurons alternate between ON periods of firing and OFF periods of silence. This bi-stability, which is largely synchronous across neurons, is reflected in the EEG as slow waves. Slow-wave activity (SWA) increases with wake duration and declines homeostatically during sleep, but the underlying mechanisms remain unclear. One possibility is neuronal "fatigue": high, sustained firing in wake would force neurons to recover with more frequent and longer OFF periods during sleep. Another possibility is net synaptic potentiation during wake: stronger coupling among neurons would lead to greater synchrony and therefore higher SWA. Here, we obtained a comparable increase in sustained firing (6 h) in cortex by: (1) keeping mice awake by exposure to novel objects to promote plasticity and (2) optogenetically activating a local population of cortical neurons at wake-like levels during sleep. Sleep after extended wake led to increased SWA, higher synchrony, and more time spent OFF, with a positive correlation between SWA, synchrony, and OFF periods. Moreover, time spent OFF was correlated with cortical firing during prior wake. After local optogenetic stimulation, SWA and cortical synchrony decreased locally, time spent OFF did not change, and local SWA was not correlated with either measure. Moreover, laser-induced cortical firing was not correlated with time spent OFF afterward. Overall, these results suggest that high sustained firing per se may not be the primary determinant of SWA increases observed after extended wake.

Vyazovskiy VV, Cui N, Rodriguez AV, Funk C, Cirelli C, Tononi G. The dynamics of cortical neuronal activity in the first minutes after spontaneous awakening in rats and mice.

Can neurological evidence help courts assess criminal responsibility? To answer this question, we must first specify legal criteria for criminal responsibility and then ask how neurological findings can be used to determine whether particular defendants meet those criteria. Cognitive neuroscience may speak to at least two familiar conditions of criminal responsibility: intention and sanity. Functional neuroimaging studies in motor planning, awareness of actions, agency, social contract reasoning, and theory of mind, among others, have recently targeted a small assortment of brain networks thought to be instrumental in such determinations. Advances in each of these areas bring specificity to the problems underlying the application of neuroscience to criminal law.

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SUMMARYCortical slow waves – the hallmark of NREM sleep - reflect near-synchronous OFF periods in cortical neurons. However, the mechanisms triggering such OFF periods are unclear, as there is little evidence for somatic inhibition. We studied cortical inhibitory interneurons that express somatostatin (SOM), because ∼70% of them are Martinotti cells that target diffusely layer 1 and can block excitatory transmission presynaptically, at glutamatergic terminals, and postsynaptically, at apical dendrites, without inhibiting the soma. In freely moving mice, we show that SOM+ cells can fire immediately before slow waves and their optogenetic stimulation triggers neuronal OFF periods during sleep. Next, we show that chemogenetic activation of SOM+ cells increases slow wave activity (SWA), the slope of individual slow waves, and the duration of NREM sleep; whereas their chemogenetic inhibition decreases SWA and slow wave incidence without changing time spent asleep. By contrast, activation of parvalbumin+ (PV+) cells, the most numerous population of cortical inhibitory neurons, greatly decreases SWA and cortical firing. These results indicate that SOM+ cells, but not PV+ cells, are involved in the generation of sleep slow waves. Whether Martinotti cells are solely responsible for this effect, or are complemented by other classes of inhibitory neurons, remains to be investigated.

Sleep and anesthesia entail alterations in conscious experience. Conscious experience may be absent (unconsciousness) or take the form of dreaming, a state in which sensory stimuli are not incorporated into conscious experience (disconnected consciousness). Recent work has identified features of cortical activity that distinguish conscious from unconscious states; however, less is known about how cortical activity differs between disconnected states and normal wakefulness. We employed transcranial magnetic stimulation–electroencephalography (TMS–EEG) over parietal regions across states of anesthesia and sleep to assess whether evoked oscillatory activity differed in disconnected states. We hypothesized that alpha activity, which may regulate perception of sensory stimuli, is altered in the disconnected states of rapid eye movement (REM) sleep and ketamine anesthesia. Compared to wakefulness, evoked alpha power (8–12 Hz) was decreased during disconnected consciousness. In contrast, in unconscious states of propofol anesthesia and non-REM (NREM) sleep, evoked low-gamma power (30–40 Hz) was decreased compared to wakefulness or states of disconnected consciousness. These findings were confirmed in subjects in which dream reports were obtained following serial awakenings from NREM sleep. By examining signatures of evoked cortical activity across conscious states, we identified novel evidence that suppression of evoked alpha activity may represent a promising marker of sensory disconnection.