Optogenetic activation of dopamine neurons in the ventral tegmental area induces reanimation from general anesthesia

Taylor, Norman E.; Dort, Christa J. Van; Kenny, Jonathan D.; Pei, JunZhu; Guidera, Jennifer A.; Vlasov, Ksenia; Lee, Justin; Boyden, Edward S.; Brown, Emery N.; Solt, Ken

doi:10.1073/pnas.1614340113

Cited by 219 publications

(198 citation statements)

References 55 publications

Supporting

Mentioning

179

Contrasting

Order By: Relevance

“…For example, in both mammals and insects, dopaminergic (mammals: [8 •• ,9 •• ]; insects: [10,11]), noradrenergic (mammals: [12]; insects: [13]), and histaminergic (mammals: [14]; insects: [15]) transmissions promote wakefulness, while GABAergic (mammals: [4 • ]; insects: [16,17]) and serotonergic (mammals: [18]; insects: [19]) transmissions promote sleep. This conservation suggests an ancient and common origin for sleep [6].…”

Section: Neuronal Circuitry Of Sleep/wake State Regulationmentioning

confidence: 99%

To sleep or not to sleep: neuronal and ecological insights

Eban-Rothschild

Giardino

Lecea

2017

Current Opinion in Neurobiology

View full text Add to dashboard Cite

Daily, animals need to decide when to stop engaging in cognitive processes and behavioral responses to the environment, and go to sleep. The main processes regulating the daily organization of sleep and wakefulness are circadian rhythms and homeostatic sleep pressure. In addition, motivational processes such as food seeking and predator evasion can modulate sleep/wake behaviors. Here, we discuss the principal processes regulating the propensity to stay awake or go to sleep—focusing on neuronal and behavioral aspects. We first introduce the neuronal populations involved in sleep/wake regulation. Next, we describe the circadian and homeostatic drives for sleep. Then, we highlight studies demonstrating various effects of motivational processes on sleep/wake behaviors, and discuss possible neuronal mechanisms underlying their control.

show abstract

Section: Neuronal Circuitry Of Sleep/wake State Regulationmentioning

confidence: 99%

To sleep or not to sleep: neuronal and ecological insights

Eban-Rothschild

Giardino

Lecea

2017

Current Opinion in Neurobiology

View full text Add to dashboard Cite

show abstract

“…Since the righting reflex varies during the emergence from anesthesia, it is difficult to assess the onset of awakening using this metric. For instance, several groups 3-6,33,39 have used the righting reflex as a surrogate for arousal. However, righting reflex alone seems unspecific.…”

Section: Discussionmentioning

confidence: 99%

Continuous regimens of cortico-motor integration calibrate levels of arousal during emergence from anesthesia

Gao

Calderon

2020

Preprint

View full text Add to dashboard Cite

31Background: Recovery to a conscious state when emerging from anesthesia requires 32 full cortical desynchronization, initiation of movement and behavioral reactivity to 33 sensory stimuli. However, the variety of cortical electroencephalogram (EEG) patterns 34 associated with specific anesthetics and the paucity of behavioral descriptions during 35 emergence from anesthesia have prevented EEG and behavior as feasible tracking 36 methods to assess emerging from anesthesia. We propose a detailed combined 37 analysis of motor and cortical activity to determine levels of arousal in rodents. 39Methods: Using decreasing anesthetic concentrations, we simultaneously recorded 40 local field potentials (LFPs) and movement in mice. We delineated cortical dynamics 41 and sub-states during emergence from anesthesia by applying a smoothed-Z score to 42 extract dominant frequencies from spectrogram. Then, we implemented KMeans to 43 obtain cortical sub-states. Finally, we used density estimation and an abrupt change 44 detection algorithm to segment cortical activity into periods. We used cortical sub-states 45 obtained during isoflurane traces to supervise sub-states in sevoflurane and a 46 pharmacologically induced-arousal model. This information together with examining 47 videos were used to categorize behavior. 49Results: We identified five cortical periods with restored motor behavior during 50 emergence from isoflurane anesthetic. Periods of structured sub-states denoted when 51 specific motor behaviors occurred. No significant differences were found when 52 comparing the combined cortical features and motor behavior using isoflurane, 53 3 sevoflurane and our arousal-rodent model. We describe graded regimens of cortico-54 motor activity during emergence from anesthesia to assess arousal levels. 55 56 Conclusion: We show cortical patterns denote gradual motor behaviors when emerging 57 from anesthesia. Restoring motor behavior is a dynamic process that begins tens of 58 minutes earlier than the righting reflex. Combining cortical activity and motor behavior 59 unveils novel biomarkers to accurately track emerging from general anesthesia in 60 rodents and likely other species. 61 62 Key words: Emergence from anesthesia, movement, behavioral arousal, cortical 63 biomarkers, cortical periods, spectral analysis, smoothed Z score algorithm, k-means 64 classifier, righting reflex 65 66 67 68 69 70 71 72 4Introduction: 73 Recovery to a conscious state in humans usually comprises full cortical 74 desynchronization, initiation of movement and behavioral reactivity to sensory stimuli 1 . 75 However, the combination of these parameters in rodents is rarely used when assessing 76 arousal when emerging from anesthesia 2 or when investigating the neuronal pathways 77 underlying reversing anesthetic states in animal models 3-6 . A clear discrepancy arises 78 when analyzing cortical activity 7 and behavior among anesthetics. Some data suggests 79 excluding these parameters. For example, the onset of movement during the emergence 8...

show abstract

“…Proper monitoring of anesthesia conditions is of the highest importance to further explore the mechanisms that lead to effective anesthesia (Irifune et al, 2000;Solt et al, 2014;Zhou et al, 2015;Taylor et al, 2016), as well as to prevent unnecessary pain, discomfort and distress (Gaertner et al, 2008;Smith and Danneman, 2008;Hellebrekers and Hedenqvist, 2010), side effects known to impact on cognitive (Shields et al, 2016) and molecular readouts (Black, 2002). In rodents, the presence/absence of reflexes to noxious stimuli (e.g.…”

Section: Introductionmentioning

confidence: 99%

MORPhA Scale: behavioral and electroencephalographic validation of a rodent anesthesia scale

Esteves

Almeida

Silva

et al. 2018

Preprint

View full text Add to dashboard Cite

Degree of anesthesia in laboratory rodents is normally evaluated by testing loss of reflexes. While these are useful endpoint assessments, they are of limited application to study induction/reversal kinetics or factors affecting individual susceptibility (e.g. sex or age). We developed and validated a grading system for a temporal follow up of anesthesia. The Minho Objective Rodent Phenotypical Anesthesia (MORPhA) scale was tested in mice and rats anaesthetized with a mixture of ketamine/dexmedetomidine (ket/dex -3 doses). The scale comprises 12 behavioral readouts organized in 5 stages -(i) normal/(ii) hindered voluntary movement, elicited response to (iii) non-noxious/(iv) noxious stimuli and (v) absence of responseevaluated at regular time points. Progression across stages was monitored by electroencephalography (EEG) in rats during anesthesia induction and reversal (atipamezole) and during induction with a second anesthetic drug (pentobarbital). Higher anesthetic doses decreased the time to reach higher levels of anesthesia during progression, while increasing the time to regain waking behavior during reversal, in mice and in rats. A regular decrease in high frequencies (low and high gamma) power was observed as the MORPhA score increased during anesthesia induction, while the opposite pattern was observed during emergence from anesthesia through reversion of dex effect. The devised anesthetic scale is of simple application and provides a semi-quantifiable readout of anesthesia induction/reversal.

show abstract

Optogenetic activation of dopamine neurons in the ventral tegmental area induces reanimation from general anesthesia

Cited by 219 publications

References 55 publications

To sleep or not to sleep: neuronal and ecological insights

To sleep or not to sleep: neuronal and ecological insights

Continuous regimens of cortico-motor integration calibrate levels of arousal during emergence from anesthesia

MORPhA Scale: behavioral and electroencephalographic validation of a rodent anesthesia scale

Contact Info

Product

Resources

About