scholarly journals Locus coeruleus norepinephrine activity mediates sensory-evoked awakenings from sleep

2020 ◽  
Vol 6 (15) ◽  
pp. eaaz4232 ◽  
Author(s):  
Hanna Hayat ◽  
Noa Regev ◽  
Noa Matosevich ◽  
Anna Sales ◽  
Elena Paredes-Rodriguez ◽  
...  

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.

2019 ◽  
Author(s):  
Hanna Hayat ◽  
Noa Regev ◽  
Noa Matosevich ◽  
Anna Sales ◽  
Elena Paredes-Rodriguez ◽  
...  

AbstractA defining feature of sleep is reduced responsiveness to external stimuli, but the mechanisms gating sensory-evoked arousal remain unclear. We hypothesized that reduced locus-coeruleus norepinephrine (LC-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 of 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. Importantly, liminal 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.


2020 ◽  
Author(s):  
Mathew L Rynes ◽  
Daniel Surinach ◽  
Samantha Linn ◽  
Michael Laroque ◽  
Vijay Rajendran ◽  
...  

ABSTRACTThe advent of genetically encoded calcium indicators, along with surgical preparations such as thinned skulls or refractive index matched skulls, have enabled mesoscale cortical activity imaging in head-fixed mice. Such imaging studies have revealed complex patterns of coordinated activity across the cortex during spontaneous behaviors, goal-directed behavior, locomotion, motor learning, and perceptual decision making. However, neural activity during unrestrained behavior significantly differs from neural activity in head-fixed animals. Whole-cortex imaging in freely behaving mice will enable the study of neural activity in a larger, more complex repertoire of behaviors not possible in head-fixed animals. Here we present the “Mesoscope,” a wide-field miniaturized, head-mounted fluorescence microscope compatible with transparent polymer skulls recently developed by our group. With a field of view of 8 mm x 10 mm and weighing less than 4 g, the Mesoscope can image most of the mouse dorsal cortex with resolution ranging from 39 to 56 µm. Stroboscopic illumination with blue and green LEDs allows for the measurement of both fluorescence changes due to calcium activity and reflectance signals to capture hemodynamic changes. We have used the Mesoscope to successfully record mesoscale calcium activity across the dorsal cortex during sensory-evoked stimuli, open field behaviors, and social interactions. Finally, combining the mesoscale imaging with electrophysiology enabled us to measure dynamics in extracellular glutamate release in the cortex during the transition from wakefulness to natural sleep.


2020 ◽  
pp. 146735842097275
Author(s):  
Dora Agapito ◽  
Patrícia Pinto ◽  
Mário Passos Ascenção ◽  
Pasi Tuominen

Well-designed experiencescapes are deemed a key factor in the marketing of tourist experiences aiming at positive tourists’ responses. However, this aspect has been underrepresented in empirical research focused on accommodation businesses. This study proposes the construct compelling accommodationscape and empirically tests a theoretical framework in a rural context through the lens of experiential marketing. The proposed construct is presented as the external stimuli that underlie an engaging context of the guest experience in lodging units, based on the idea that a holistic approach to stimuli can evoke interest and attention; and, subsequently, act as a driver to positive action. Apart from physical stimuli and staff performance, which have been the factors more commonly examined in services marketing, the construct compelling accommodationscape extends the servicescape approach by also addressing product-related factors, the existence of a theme and social interactions. Structural equation modelling applied to data from a survey administered in rural lodgings in Southwest Portugal supports that the five external factors underlie the proposed construct. In turn, compelling accommodationscape is positively related to tourists’ satisfaction and positive behavioural intentions. Theoretical and practical implications are provided for scholars and rural accommodation managers.


2012 ◽  
Vol 37 (9) ◽  
pp. 2020-2030 ◽  
Author(s):  
David M Devilbiss ◽  
Barry D Waterhouse ◽  
Craig W Berridge ◽  
Rita Valentino

Cell Reports ◽  
2017 ◽  
Vol 20 (13) ◽  
pp. 3099-3112 ◽  
Author(s):  
Yang Liu ◽  
Charles Rodenkirch ◽  
Nicole Moskowitz ◽  
Brian Schriver ◽  
Qi Wang

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