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.

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 Neural substrates of propranolol-induced impairments in the reconsolidation of nicotine-associated memories in smokers

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiao Lin ◽  
Jiahui Deng ◽  
Kai Yuan ◽  
Qiandong Wang ◽  
Lin Liu ◽  
...  
Keyword(s):  
Neural Activity ◽  
Neural Substrates ◽  
Brain Regions ◽  
Reward Processing ◽  
Memory Reconsolidation ◽  
Functional Magnetic Resonance ◽  
Resonance Imaging ◽  
Postcentral Gyrus ◽  
Propranolol Group ◽  
Propranolol Administration

AbstractThe majority of smokers relapse even after successfully quitting because of the craving to smoking after unexpectedly re-exposed to smoking-related cues. This conditioned craving is mediated by reward memories that are frequently experienced and stubbornly resistant to treatment. Reconsolidation theory posits that well-consolidated memories are destabilized after retrieval, and this process renders memories labile and vulnerable to amnestic intervention. This study tests the retrieval reconsolidation procedure to decrease nicotine craving among people who smoke. In this study, 52 male smokers received a single dose of propranolol (n = 27) or placebo (n = 25) before the reactivation of nicotine-associated memories to impair the reconsolidation process. Craving for smoking and neural activity in response to smoking-related cues served as primary outcomes. Functional magnetic resonance imaging was performed during the memory reconsolidation process. The disruption of reconsolidation by propranolol decreased craving for smoking. Reactivity of the postcentral gyrus in response to smoking-related cues also decreased in the propranolol group after the reconsolidation manipulation. Functional connectivity between the hippocampus and striatum was higher during memory reconsolidation in the propranolol group. Furthermore, the increase in coupling between the hippocampus and striatum positively correlated with the decrease in craving after the reconsolidation manipulation in the propranolol group. Propranolol administration before memory reactivation disrupted the reconsolidation of smoking-related memories in smokers by mediating brain regions that are involved in memory and reward processing. These findings demonstrate the noradrenergic regulation of memory reconsolidation in humans and suggest that adjunct propranolol administration can facilitate the treatment of nicotine dependence. The present study was pre-registered at ClinicalTrials.gov (registration no. ChiCTR1900024412).

scholarly journals Dissociable oscillatory networks support gain and loss processing in human orbitofrontal cortex

2021 ◽  
Author(s):  
Ignacio Saez ◽  
Jack Lin ◽  
Edward Chang ◽  
Josef Parvizi ◽  
Robert T. Knight ◽  
...  
Keyword(s):  
Neural Activity ◽  
Orbitofrontal Cortex ◽  
Low Frequency ◽  
Brain Regions ◽  
Reward Processing ◽  
Neural Oscillations ◽  
Beta Band ◽  
Neuronal Ensembles ◽  
Gain And Loss

AbstractHuman neuroimaging and animal studies have linked neural activity in orbitofrontal cortex (OFC) to valuation of positive and negative outcomes. Additional evidence shows that neural oscillations, representing the coordinated activity of neuronal ensembles, support information processing in both animal and human prefrontal regions. However, the role of OFC neural oscillations in reward-processing in humans remains unknown, partly due to the difficulty of recording oscillatory neural activity from deep brain regions. Here, we examined the role of OFC neural oscillations (<30Hz) in reward processing by combining intracranial OFC recordings with a gambling task in which patients made economic decisions under uncertainty. Our results show that power in different oscillatory bands are associated with distinct components of reward evaluation. Specifically, we observed a double dissociation, with a selective theta band oscillation increase in response to monetary gains and a beta band increase in response to losses. These effects were interleaved across OFC in overlapping networks and were accompanied by increases in oscillatory coherence between OFC electrode sites in theta and beta band during gain and loss processing, respectively. These results provide evidence that gain and loss processing in human OFC are supported by distinct low-frequency oscillations in networks, and provide evidence that participating neuronal ensembles are organized functionally through oscillatory coherence, rather than local anatomical segregation.

scholarly journals Hypercapnic hyperventilation shortens emergence time from Propofol and Isoflurane anesthesia

2013 ◽  
Vol 2 (1) ◽  
pp. 24
Author(s):  
Mohammad Golparvar ◽  
Ali Mehrabi ◽  
Hossein Sateie ◽  
Reihanak Talakoub ◽  
Ahmad Yaraghi
Keyword(s):  
Emergence Time ◽  
Isoflurane Anesthesia

New Approaches for the Quantification and Targeting of Noradrenergic Dysfunction in Alzheimer’s Disease

2021 ◽  
Author(s):  
Michael David ◽  
Paresh A. Malhotra
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Locus Coeruleus ◽  
Neuropsychiatric Symptoms ◽  
Structural Mri ◽  
Brain Regions ◽  
Small Scale ◽  
Symptomatic Therapy ◽  
Pontine Nucleus ◽  
Individual Level

There is clear and early noradrenergic dysfunction in Alzheimer’s disease. This is likely secondary to pathological tau deposition in the locus coeruleus, the pontine nucleus that produces and releases noradrenaline, which occurs prior to involvement of cortical brain regions. Disruption of noradrenergic pathways affects cognition, especially attention, which impacts on memory and broader functioning in daily life. Additionally, it leads to the autonomic and neuropsychiatric symptoms that are frequently observed with disease progression.Despite the strong evidence of noradrenergic involvement in Alzheimer’s, there are no clear trial data supporting the clinical use of any noradrenergic treatments. Several approaches have been tried, including both proof-of-principle studies and randomised controlled trials, although most of the latter have been relatively small scale. Treatments have included drug therapies as well as stimulation modalities thought to modulate noradrenergic transmission. The lack of clear positive findings is likely secondary to limited capacity for gauging locus coeruleus integrity and noradrenergic dysfunction at an individual level. However, the recent development of several novel biomarkers holds potential and should allow quantification of dysfunction. This in turn may inform inclusion criteria and stratification for future trials. Imaging approaches in particular have improved greatly following the development of neuromelanin-sensitive sequences, enabling the use of structural MRI scans to estimate locus coeruleus integrity. Additionally, functional MRI and PET scanning have the potential to quantify network dysfunction. As well as neuroimaging, EEG and pupillometry techniques may prove useful in assessing noradrenergic tone and dynamic response to stimulation.Here we review the development of these biomarkers and discuss how they might augment clinical studies, particularly randomised trials, through stratification and identification of patients most likely to benefit from treatment. We outline the biomarkers with most potential, and how they hold promise as a means of transforming symptomatic therapy for people living with Alzheimer’s disease.

Abstract WMP117: Regional Homogeneity Changes In Patients With Transient Ischemic Attack: A Resting-state Functional Magnetic Resonance Imaging Study

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Jian Guo ◽  
Ning Chen ◽  
Muke Zhou ◽  
Pian Wang ◽  
Li He
Keyword(s):  
Transient Ischemic Attack ◽  
Neural Activity ◽  
Resting State ◽  
Right Hemisphere ◽  
Brain Activity ◽  
Imaging Study ◽  
Brain Regions ◽  
Regional Homogeneity ◽  
Anterior Cingulate ◽  
Ischemic Attack

Background: Transient ischemic attack (TIA) can increase the risk of some neurologic dysfunctions, of which the mechanism remains unclear. Resting-state functional MRI (rfMRI) is suggested to be a valuable tool to study the relation between spontaneous brain activity and behavioral performance. However, little is known about whether the local synchronization of spontaneous neural activity is altered in TIA patients. The purpose of this study is to detect differences in regional spontaneous activities throughout the whole brain between TIAs and normal controls. Methods: Twenty one TIA patients suffered an ischemic event in the right hemisphere and 21 healthy volunteers were enrolled in the study. All subjects were investigated using cognitive tests and rfMRI. The regional homogeneity (ReHo) was calculate and compared between two groups. Then a correlation analysis was performed to explore the relationship between ReHo values of brain regions showing abnormal resting-state properties and clinical variables in TIA group. Results: Compared with controls, TIA patients exhibited decreased ReHo in right dorsolateral prefrontal cortex (DLPFC), right inferior prefrontal gyrus, right ventral anterior cingulate cortex and right dorsal posterior cingular cortex. Moreover, the mean ReHo in right DLPFC and right inferior prefrontal gyrus were significantly correlated with MoCA in TIA patients. Conclusions: Neural activity in the resting state is changed in patients with TIA. The positive correlation between regional homogeneity of rfMRI and cognition suggests that ReHo may be a promising tool to better our understanding of the neurobiological consequences of TIA.

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