A defining feature of sleep is reduced responsiveness to external stimuli, but the mechanisms mediating sensory-evoked arousal remain unclear. We hypothesized that reduced locus coeruleus (LC) norepinephrine (NE) activity during sleep mediates unresponsiveness, and its action promotes sensory-evoked awakenings. We tested this using electrophysiological, behavioral, pharmacological, and optogenetic techniques alongside auditory stimulation in freely behaving rats. We found that systemic reduction in NE signaling lowered probability of sound-evoked awakenings (SEAs). The level of tonic LC activity during sleep anticipated SEAs. Optogenetic LC activation promoted arousal as evident in sleep-wake transitions, EEG desynchronization, and pupil dilation. Minimal LC excitation before sound presentation increased SEA probability. Optogenetic LC silencing using a soma-targeted anion-conducting channelrhodopsin (stGtACR2) suppressed LC spiking and constricted pupils. Brief periods of LC opto-silencing reduced the probability of SEAs. Thus, LC-NE activity determines the likelihood of sensory-evoked awakenings, and its reduction during sleep constitutes a key factor mediating behavioral unresponsiveness.
A fundamental feature of sleep is reduced behavioral responsiveness to external events, but the extent of processing along sensory pathways remains poorly understood. While responses are comparable across wakefulness and sleep in auditory cortex (AC), neuronal activity in downstream regions remains unknown. Here we recorded spiking activity in 435 neuronal clusters evoked by acoustic stimuli in the perirhinal cortex (PRC) and in AC of freely behaving male rats across wakefulness and sleep. Neuronal responses in AC showed modest (ϳ10%) differences in response gain across vigilance states, replicating previous studies. By contrast, PRC neuronal responses were robustly attenuated by 47% and 36% during NREM sleep and REM sleep, respectively. Beyond the separation according to cortical region, response latency in each neuronal cluster was correlated with the degree of NREM sleep attenuation, such that late (Ͼ40 ms) responses in all monitored regions diminished during NREM sleep. The robust attenuation of late responses prevalent in PRC represents a novel neural correlate of sensory disconnection during sleep, opening new avenues for investigating the mediating mechanisms.
During sleep, sensory stimuli rarely trigger a behavioral response or conscious perception. However, it remains unclear whether sleep inhibits specific aspects of sensory processing, such as feedforward or feedback signaling. Here, we presented auditory stimuli (for example, click-trains, words, music) during wakefulness and sleep in patients with epilepsy, while recording neuronal spiking, microwire local field potentials, intracranial electroencephalogram and polysomnography. Auditory stimuli induced robust and selective spiking and high-gamma (80–200 Hz) power responses across the lateral temporal lobe during both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. Sleep only moderately attenuated response magnitudes, mainly affecting late responses beyond early auditory cortex and entrainment to rapid click-trains in NREM sleep. By contrast, auditory-induced alpha–beta (10–30 Hz) desynchronization (that is, decreased power), prevalent in wakefulness, was strongly reduced in sleep. Thus, extensive auditory responses persist during sleep whereas alpha–beta power decrease, likely reflecting neural feedback processes, is deficient. More broadly, our findings suggest that feedback signaling is key to conscious sensory processing.
Number of multimedia and 3D models: 0 Number of words for abstract (max 250): 171 Number of words for introduction (max 650): 596 Number of words for discussion (max 1500): 919Reduced behavioral responsiveness to sensory stimulation is at the core of sleep's definition, but it is still unclear how the sleeping brain responds differently to sensory stimuli. In the current study we recorded neuronal spiking responses to sounds along the cortical processing hierarchy of rats during wakefulness and natural sleep. Responses in auditory cortex only showed modest changes during sleep, whereas sleep robustly attenuated the responses of neurons in high-level perirhinal cortex. We also found that during NREM sleep, the response latency predicts the degree of sleep attenuation in individual neurons above and beyond their anatomical location. These results provide anatomical and temporal signatures of sensory disconnection during sleep and pave the way to understanding the underlying mechanisms.
SummaryA predicted difficult airway is sometimes considered a contra-indication to rapid sequence induction of general anaesthesia, even in an urgent case such as a category-1 caesarean section for fetal distress. However, formally assessing the risk is difficult because of the rarity and urgency of such cases. We have used decision analysis to quantify the time taken to establish anaesthesia, and probability of failure, of three possible anaesthetic methods, based on a systematic review of the literature. We considered rapid sequence induction of general anaesthesia with videolaryngoscopy, awake fibreoptic intubation and rapid spinal anaesthesia. Our results show a shorter mean (95% CI) time to induction of 100 (87-114) s using rapid sequence induction compared with 9 (7-11) min for awake fibreoptic intubation (p < 0.0001) and 6.3 (5.4-7.2) min for spinal anaesthesia (p < 0.0001). We calculate the risk of ultimate failed airway control after rapid sequence induction to be 21 (0-53) per 100,000 cases, and postulate that some mothers may accept such a risk in order to reduce potential fetal harm from an extended time interval until delivery. Although rapid sequence induction may not be the anaesthetic technique of choice for all cases in the circumstance of a category-1 caesarean section for fetal distress with a predicted difficult airway, we suggest that it is an acceptable option.
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