scholarly journals Designer receptor manipulations reveal a role of the locus coeruleus noradrenergic system in isoflurane general anesthesia

2014 ◽  
Vol 111 (10) ◽  
pp. 3859-3864 ◽  
Author(s):  
Elena M. Vazey ◽  
Gary Aston-Jones
Keyword(s):  
General Anesthesia ◽  
Locus Coeruleus ◽  
Noradrenergic System ◽  
Cortical Arousal ◽  
General Anesthetic ◽  
Clinical Safety ◽  
Isoflurane Anesthesia ◽  
Eeg Activation ◽  
Eeg Power

Mechanisms driving emergence from general anesthesia are not well understood. The noradrenergic brain nucleus locus coeruleus (LC) modulates arousal and may have effects on general anesthetic state. Using virally delivered designer receptors to specifically control LC norepinephrine (NE) neurons, we investigated the causal relationship between LC-NE activity and general anesthetic state under isoflurane. Selective activation of LC-NE neurons produced cortical electroencephalography (EEG) activation under continuous deep isoflurane anesthesia. Specifically, LC-NE activation reduced burst suppression in EEG and drove a rightward shift in peak EEG frequency with reduced δ EEG power and increased θ EEG power, measures of cortical arousal. LC-NE activation also accelerated behavioral emergence from deep isoflurane anesthesia; this was prevented with β or α1 noradrenergic antagonists. Moreover, these adrenoreceptor antagonists alone were sufficient to markedly potentiate anesthetic duration when delivered centrally or peripherally. Induction of anesthesia also was retarded by LC-NE activation. Our results demonstrate that the LC-NE system strongly modulates the anesthetic state, and that changes in LC-NE neurotransmission alone can affect the emergence from isoflurane general anesthesia. Taken together, these findings extend our understanding of mechanisms underlying general anesthesia and cortical arousal, and have significant implications for optimizing the clinical safety and management of general anesthesia.

scholarly journals Locus Coeruleus to Paraventricular Thalamus Projections Facilitate Emergence From Isoflurane Anesthesia in Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Yawen Ao ◽  
Bo Yang ◽  
Caiju Zhang ◽  
Bo Wu ◽  
Xuefen Zhang ◽  
...  
Keyword(s):  
Locus Coeruleus ◽  
Neural Activity ◽  
Brain Regions ◽  
Cortical Arousal ◽  
Emergence Time ◽  
General Anesthetic ◽  
Common Pathway ◽  
Isoflurane Anesthesia ◽  
New Strategy ◽  
Paraventricular Thalamus

Locus coeruleus (LC) sends widespread outputs to many brain regions to modulate diverse functions, including sleep/wake states, attention, and the general anesthetic state. The paraventricular thalamus (PVT) is a critical thalamic area for arousal and receives dense tyrosine-hydroxylase (TH) inputs from the LC. Although anesthesia and sleep may share a common pathway, it is important to understand the processes underlying emergence from anesthesia. In this study, we hypothesize that LC TH neurons and the TH:LC-PVT circuit may be involved in regulating emergence from anesthesia. Only male mice are used in this study. Here, using c-Fos as a marker of neural activity, we identify LC TH expressing neurons are active during anesthesia emergence. Remarkably, chemogenetic activation of LC TH neurons shortens emergence time from anesthesia and promotes cortical arousal. Moreover, enhanced c-Fos expression is observed in the PVT after LC TH neurons activation. Optogenetic activation of the TH:LC-PVT projections accelerates emergence from anesthesia, whereas, chemogenetic inhibition of the TH:LC-PVT circuit prolongs time to wakefulness. Furthermore, optogenetic activation of the TH:LC-PVT projections produces electrophysiological evidence of arousal. Together, these results demonstrate that activation of the TH:LC-PVT projections is helpful in facilitating the transition from isoflurane anesthesia to an arousal state, which may provide a new strategy in shortening the emergence time after general anesthesia.

GABAergic Neurons in the Dorsal–Intermediate Lateral Septum Regulate Sleep–Wakefulness and Anesthesia in Mice

2021 ◽  
Author(s):  
Di Wang ◽  
Qingchen Guo ◽  
Yu Zhou ◽  
Zheng Xu ◽  
Su-Wan Hu ◽  
...  
Keyword(s):  
General Anesthesia ◽  
Eye Movement ◽  
Gabaergic Neurons ◽  
Lateral Septum ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
Awake State ◽  
Isoflurane Anesthesia

Background The γ-aminobutyric acid–mediated (GABAergic) inhibitory system in the brain is critical for regulation of sleep–wake and general anesthesia. The lateral septum contains mainly GABAergic neurons, being cytoarchitectonically divided into the dorsal, intermediate, and ventral parts. This study hypothesized that GABAergic neurons of the lateral septum participate in the control of wakefulness and promote recovery from anesthesia. Methods By employing fiber photometry, chemogenetic and optogenetic neuronal manipulations, anterograde tracing, in vivo electrophysiology, and electroencephalogram/electromyography recordings in adult male mice, the authors measured the role of lateral septum GABAergic neurons to the control of sleep–wake transition and anesthesia emergence and the corresponding neuron circuits in arousal and emergence control. Results The GABAergic neurons of the lateral septum exhibited high activities during the awake state by in vivo fiber photometry recordings (awake vs. non–rapid eye movement sleep: 3.3 ± 1.4% vs. –1.3 ± 1.2%, P < 0.001, n = 7 mice/group; awake vs. anesthesia: 2.6 ± 1.2% vs. –1.3 ± 0.8%, P < 0.001, n = 7 mice/group). Using chemogenetic stimulation of lateral septum GABAergic neurons resulted in a 100.5% increase in wakefulness and a 51.2% reduction in non–rapid eye movement sleep. Optogenetic activation of these GABAergic neurons promoted wakefulness from sleep (median [25th, 75th percentiles]: 153.0 [115.9, 179.7] s to 4.0 [3.4, 4.6] s, P = 0.009, n = 5 mice/group) and accelerated emergence from isoflurane anesthesia (514.4 ± 122.2 s vs. 226.5 ± 53.3 s, P < 0.001, n = 8 mice/group). Furthermore, the authors demonstrated that the lateral septum GABAergic neurons send 70.7% (228 of 323 cells) of monosynaptic projections to the ventral tegmental area GABAergic neurons, preferentially inhibiting their activities and thus regulating wakefulness and isoflurane anesthesia depth. Conclusions The results uncover a fundamental role of the lateral septum GABAergic neurons and their circuit in maintaining awake state and promoting general anesthesia emergence time. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

scholarly journals Examining the Role of the Noradrenergic Locus Coeruleus for 2 Predicting Attention and Brain Maintenance in Healthy Old Age 3 and Disease: An MRI Structural Study for the Alzheimer’s Disease 4 Neuroimaging Initiative

2021 ◽  
Author(s):  
Emanuele Raffaele Giuliano Plini ◽  
Erik O'Hanlon ◽  
Rory Boyle ◽  
Francesca Sibilia ◽  
Gaia Rikhye ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Locus Coeruleus ◽  
Objective Measure ◽  
Cognitive Stimulation ◽  
Noradrenergic System ◽  
Dietary Interventions ◽  
Biological Index ◽  
Attentional Performance ◽  
Brain Maintenance

The noradrenergic theory of Cognitive Reserve (Robertson, 2013-2014) postulates that the upregulation of the Locus Coeruleus - Noradrenergic System (LC-NA) originating in the Brainstem might facilitate cortical networks involved in attention, and protracted activation of this system throughout the lifespan may enhance cognitive stimulation contributing to Reserve. To test the above-mentioned theory, a study was conducted on a sample of 686 participants (395 controls, 156 Mild Cognitive Impairment, 135 Alzheimer’s Disease) investigating the relationship between LC volume, attentional performance and a biological index of brain maintenance (BrainPAD – an objective measure which compares an individual’s structural brain health, reflected by their voxel-wise grey matter density, to the state typically expected at that individual’s age). Further analyses were carried out on Reserve indices including education and occupational attainment. Volumetric variation across groups was also explored along with gender differences. Control analyses on the Serotoninergic (5-HT), Dopaminergic (DA) and Cholinergic (Ach) systems were contrasted with the Noradrenergic (NA) hypothesis. The antithetic relationships were also tested across the neuromodulatory subcortical systems.Results supported by bayesian modelling showed that LC volume disproportionately predicted higher attentional performance as well as biological brain maintenance across the three groups. These findings lend support to the role of the noradrenergic system as a key mediator underpinning the neuropsychology of Reserve, and they suggest that early prevention strategies focused on the noradrenergic system (e.g. cognitive-attentive training, physical exercise, pharmacological and dietary interventions) may yield important clinical benefits to mitigate cognitive impairment with age and disease.

scholarly journals Examining the Role of the Noradrenergic Locus Coeruleus for 2 Predicting Attention and Brain Maintenance in Healthy Old Age 3 and Disease: An MRI Structural Study for the Alzheimer’s Disease 4 Neuroimaging Initiative

2021 ◽  
Author(s):  
Emanuele Raffaele Giuliano Plini ◽  
Erik O'Hanlon ◽  
Rory Boyle ◽  
Francesca Sibilia ◽  
Gaia Rikhye ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Locus Coeruleus ◽  
Objective Measure ◽  
Cognitive Stimulation ◽  
Noradrenergic System ◽  
Dietary Interventions ◽  
Biological Index ◽  
Attentional Performance ◽  
Brain Maintenance

The noradrenergic theory of Cognitive Reserve (Robertson, 2013-2014) postulates that the upregulation of the Locus Coeruleus - Noradrenergic System (LC-NA) originating in the Brainstem might facilitate cortical networks involved in attention, and protracted activation of this system throughout the lifespan may enhance cognitive stimulation contributing to Reserve. To test the above-mentioned theory, a study was conducted on a sample of 686 participants (395 controls, 156 Mild Cognitive Impairment, 135 Alzheimer’s Disease) investigating the relationship between LC volume, attentional performance and a biological index of brain maintenance (BrainPAD – an objective measure which compares an individual’s structural brain health, reflected by their voxel-wise grey matter density, to the state typically expected at that individual’s age). Further analyses were carried out on Reserve indices including education and occupational attainment. Volumetric variation across groups was also explored along with gender differences. Control analyses on the Serotoninergic (5-HT), Dopaminergic (DA) and Cholinergic (Ach) systems were contrasted with the Noradrenergic (NA) hypothesis. The antithetic relationships were also tested across the neuromodulatory subcortical systems.Results supported by bayesian modelling showed that LC volume disproportionately predicted higher attentional performance as well as biological brain maintenance across the three groups. These findings lend support to the role of the noradrenergic system as a key mediator underpinning the neuropsychology of Reserve, and they suggest that early prevention strategies focused on the noradrenergic system (e.g. cognitive-attentive training, physical exercise, pharmacological and dietary interventions) may yield important clinical benefits to mitigate cognitive impairment with age and disease.

scholarly journals The role of the descending noradrenergic system derived from the nucleus locus coeruleus in vesical function

1986 ◽  
Vol 40 ◽  
pp. 217
Author(s):  
Naoki Yoshimura ◽  
Yukihiro Ohno ◽  
Masashi Sasa ◽  
Shuji Takaori
Keyword(s):  
Locus Coeruleus ◽  
Noradrenergic System
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