Locus Coeruleus Norepinephrine in Learned Behavior: Anatomical Modularity and Spatiotemporal Integration in Targets

Frontiers in Neural Circuits, Год журнала: 2021, Номер 15

Опубликована: Июнь 7, 2021

The locus coeruleus (LC), a small brainstem nucleus, is the primary source of neuromodulator norepinephrine (NE) in brain. LC receives input from widespread brain regions, and projects throughout forebrain, brainstem, cerebellum, spinal cord. neurons release NE to control arousal, but also context variety sensory-motor behavioral functions. Despite its brain-wide effects, much about role LC-NE behavior circuits controlling activity unknown. New evidence suggests that modular input-output organization could enable transient, task-specific modulation distinct regions. Future work must further assess whether this spatial modularity coincides with functional differences subpopulations acting at specific times, how such spatiotemporal specificity might influence learned behaviors. Here, we summarize state field present new ideas on

Язык: Английский

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Optogenetics at the presynapse

Nature Neuroscience, Год журнала: 2022, Номер 25(8), С. 984 - 998

Опубликована: Июль 14, 2022

Язык: Английский

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Neuronal activity in the human amygdala and hippocampus enhances emotional memory encoding

Nature Human Behaviour, Год журнала: 2023, Номер 7(5), С. 754 - 764

Опубликована: Янв. 16, 2023

Язык: Английский

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Neurobiological basis of stress resilience

Neuron, Год журнала: 2024, Номер 112(12), С. 1911 - 1929

Опубликована: Май 24, 2024

Язык: Английский

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Stress Accelerates Defensive Responses to Looming in Mice and Involves a Locus Coeruleus-Superior Colliculus Projection

Current Biology, Год журнала: 2018, Номер 28(6), С. 859 - 871.e5

Опубликована: Март 1, 2018

Defensive responses to threatening stimuli are crucial the survival of species. While expression these is considered be instinctive and unconditional, their magnitude may affected by environmental internal factors. The neural circuits underlying this modulation still largely unknown. In mice, looming-evoked defensive mediated superior colliculus (SC), a subcortical sensorimotor integration center. We found that repeated stress caused an anxiety-like state in mice accelerated looming. Stress also induced c-fos activation locus coeruleus (LC) tyrosine hydroxylase (TH)+ neurons modified adrenergic receptor SC, suggesting possible Th::LC-SC projection involved responses. Indeed, both anterograde retrograde tracing confirmed anatomical SC-projecting TH+ LC were activated stress. Optogenetic stimulation either or fibers behaviors Meanwhile, chemogenetic inhibition infusion antagonist SC abolished enhanced looming after stress, confirming necessity pathway. These findings suggest pathway plays key role sophisticated adjustments changes physiological states.

Язык: Английский

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Noradrenergic targets for the treatment of alcohol use disorder

Psychopharmacology, Год журнала: 2018, Номер 235(6), С. 1625 - 1634

Опубликована: Фев. 20, 2018

Язык: Английский

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The Noradrenergic System in Parkinson’s Disease

Frontiers in Pharmacology, Год журнала: 2020, Номер 11

Опубликована: Апрель 8, 2020

Nowadays it is well accepted that in Parkinson’s disease (PD), the neurodegenerative process occurs stages and damage to other areas precedes neuronal loss substantia nigra pars compacta, which considered a pathophysiological hallmark of PD. This heterogeneous progressive neurodegeneration may explain diverse symptomatology disease, including motor non-motor alterations. In PD, one first undergoing degeneration locus coeruleus (LC). noradrenergic nucleus provides extensive innervation throughout brain plays fundamental neuromodulator role, participating stress responses, emotional memory control motor, sensory autonomic functions. Early LC neurons suffer modifications can condition effectiveness pharmacological treatments, importantly, lead appearance common symptomatology. The system also exerts anti-inflammatory neuroprotective effect on dopaminergic consequently progress disease. From point view, important understand how performs since medication often used these patients, drug interactions take place when combining them with gold standard therapy L-DOPA. review an overview about functional status PD its contribution efficacy pharmacological-based treatments. Based preclinical clinical publications, special attention will be dedicated most prevalent symptoms

Язык: Английский

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Locus coeruleus-norepinephrine modulation of sensory processing and perception: A focused review

Neuroscience & Biobehavioral Reviews, Год журнала: 2019, Номер 105, С. 190 - 199

Опубликована: Июнь 28, 2019

Язык: Английский

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Molecular and Functional Sex Differences of Noradrenergic Neurons in the Mouse Locus Coeruleus

Cell Reports, Год журнала: 2018, Номер 23(8), С. 2225 - 2235

Опубликована: Май 1, 2018

Preclinical work has long focused on male animals, though biological sex clearly influences risk for certain diseases, including many psychiatric disorders. Such disorders are often treated by drugs targeting the CNS norepinephrine system. Despite roles noradrenergic neurons in behavior and neuropsychiatric disease models, their molecular characterization lagged. We profiled mouse vivo, defining over 3,000 high-confidence transcripts expressed therein, druggable receptors. uncovered remarkable differences gene expression, elevated expression of EP3 receptor females—which we leverage to illustrate behavioral pharmacologic relevance these findings—and Slc6a15 Lin28b, both major depressive disorder (MDD)-associated genes. Broadly, present a means transcriptionally profiling locus coeruleus under baseline experimental conditions. Our findings underscore need preclinical include sexes suggest that may underlie relevant disease.

Язык: Английский

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A Discrete Dorsal Raphe to Basal Amygdala 5-HT Circuit Calibrates Aversive Memory

Neuron, Год журнала: 2019, Номер 103(3), С. 489 - 505.e7

Опубликована: Июнь 13, 2019

Highlights•Fear learning selectively engages the anatomically distinct DRN→BA 5-HT pathway•The pathway bidirectionally modulates fear and extinction•The sculpts fear-associated neuronal activity in BA•The expresses VGluT3 but drives via BA 5-HT1A/2A receptorsSummaryDespite a wealth of clinical preclinical data implicating serotonin (5-HT) system fear-related affective disorders, precise definition this neuromodulator's role remains elusive. Using convergent anatomical functional approaches, we interrogate contribution to basal amygdala (BA) inputs from dorsal raphe nucleus (DRN). We show is engaged during memory formation retrieval, these projections facilitates impairs extinction. The amplifies firing theta power phase-locking. Although recruits co-expressing DRN neurons, fear-potentiating influence requires signaling at receptors. Input-output mapping illustrates how connected with other brain regions that mediate fear. These findings reveal discrete circuit orchestrates broader neural network calibrate aversive memory.Graphical abstract

Язык: Английский

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