Endogenous and Exogenous Opioids in Pain

Annual Review of Neuroscience, Год журнала: 2018, Номер 41(1), С. 453 - 473

Опубликована: Май 31, 2018

Opioids are the most commonly used and effective analgesic treatments for severe pain, but they have recently come under scrutiny owing to epidemic levels of abuse overdose. These compounds act on endogenous opioid system, which comprises four G protein-coupled receptors (mu, delta, kappa, nociceptin) major peptide families (β-endorphin, enkephalins, dynorphins, nociceptin/orphanin FQ). In this review, we first describe functional organization pharmacology system. We then summarize current knowledge signaling mechanisms by opioids regulate neuronal function neurotransmission. Finally, discuss loci action along peripheral central pain pathways, emphasizing pain-relieving properties against affective dimension experience.

Язык: Английский

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Modular organization of the brainstem noradrenaline system coordinates opposing learning states

Nature Neuroscience, Год журнала: 2017, Номер 20(11), С. 1602 - 1611

Опубликована: Сен. 18, 2017

Язык: Английский

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Rapid Reconfiguration of the Functional Connectome after Chemogenetic Locus Coeruleus Activation

Neuron, Год журнала: 2019, Номер 103(4), С. 702 - 718.e5

Опубликована: Июнь 18, 2019

Язык: Английский

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Neural Circuit Motifs in Valence Processing

Neuron, Год журнала: 2018, Номер 100(2), С. 436 - 452

Опубликована: Окт. 1, 2018

Язык: Английский

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Molecularly defined and spatially resolved cell atlas of the whole mouse brain

Nature, Год журнала: 2023, Номер 624(7991), С. 343 - 354

Опубликована: Дек. 13, 2023

In mammalian brains, millions to billions of cells form complex interaction networks enable a wide range functions. The enormous diversity and intricate organization have impeded our understanding the molecular cellular basis brain function. Recent advances in spatially resolved single-cell transcriptomics enabled systematic mapping spatial molecularly defined cell types tissues1-3, including several regions (for example, refs. 1-11). However, comprehensive atlas whole is still missing. Here we imaged panel more than 1,100 genes approximately 10 million across entire adult mouse brains using multiplexed error-robust fluorescence situ hybridization12 performed resolved, expression profiling at whole-transcriptome scale by integrating hybridization RNA sequencing data. Using this approach, generated 5,000 transcriptionally distinct clusters, belonging 300 major types, with high resolution. Registration common coordinate framework allowed quantifications cell-type composition individual regions. We further identified modules characterized compositions gradients featuring gradual changes cells. Finally, high-resolution map cells, each transcriptome-wide profile, us infer cell-type-specific interactions between hundreds pairs predict (ligand-receptor) functional implications these cell-cell interactions. These results provide rich insights into architecture foundation for investigations neural circuits their dysfunction health disease.

Язык: Английский

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Emotional Roles of Mono-Aminergic Neurotransmitters in Major Depressive Disorder and Anxiety Disorders

Frontiers in Psychology, Год журнала: 2018, Номер 9

Опубликована: Ноя. 21, 2018

A growing body of researches support a role for dysfunction serotoninergic, noradrenergic, and dopaminergic systems in the neurobiological processes involved major depression disorder (MDD) anxiety disorders (ADs). The physiological changes underlying abnormal signaling 5-HT, NE DA may be due to either reduced presynaptic release these neurotransmitters or aberrant signal transductions, thus contributing alterations regulation function receptors and/or impaired intracellular processing. Animal models demonstrate crucial responsiveness disturbance neurotransmissions. Postmortem biochemical studies have shown altered concentrations metabolites brain regions that contribute importantly mood motivation patients with MDD ADs. Neuroimaging found binding regard receptor numbers. Medications act on neurons receptors, such as SSRIs SNRIs, show efficacy both overlapping treatment response presumably suggests common mechanism interaction disorders. In this paper, we reviewed from multiple disciplines interpret mono-amine neurotransmitter functions

Язык: Английский

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Redefining Noradrenergic Neuromodulation of Behavior: Impacts of a Modular Locus Coeruleus Architecture

Journal of Neuroscience, Год журнала: 2019, Номер 39(42), С. 8239 - 8249

Опубликована: Окт. 16, 2019

The locus coeruleus (LC) is a seemingly singular and compact neuromodulatory nucleus that prominent component of disparate theories brain function due to its broad noradrenergic projections throughout the CNS. As diffuse system, noradrenaline affects learning decision making, control sleep wakefulness, sensory salience including pain, physiology correlated forebrain activity (ensembles networks) hemodynamic responses. However, our understanding LC undergoing dramatic shift application state-of-the-art methods reveal many modules provide targeted neuromodulation. Here, we review evidence supporting modular based on multiple levels observation (developmental, genetic, molecular, anatomical, neurophysiological). We suggest concept as and, alongside it, role in diverse must be reconsidered.

Язык: Английский

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Noradrenergic Modulation of Fear Conditioning and Extinction

Frontiers in Behavioral Neuroscience, Год журнала: 2018, Номер 12

Опубликована: Март 13, 2018

The locus coeruleus norepinephrine (LC-NE) system plays a broad role in learning and memory. Here we begin with an overview of the LC-NE system. We then consider how both direct indirect manipulations affect cued contextual aversive propose that NE dynamically modulates Pavlovian conditioning extinction, either promoting or impairing processes under different levels behavioral arousal. suggest high stress (e.g., during/soon after fear conditioning) LC promotes by enhancing amygdala function while simultaneously blunting prefrontal function. Under low arousal, PFC to promote downstream inhibition foster extinction fear. Thus, action on mPFC might be described inverted-U such it can enhance hinder depending arousal states. In addition, seems particularly important for acquisition, consolidation, memories. This may due dense adrenoceptor expression hippocampus which encodes information, ability regulate long-term potentiation. Moreover, recent work reveals diversity functions memory are mediated functionally heterogeneous populations neurons defined their projection targets. Hence, is determined projection-specific neuromodulation accompanies various states

Язык: Английский

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The role of the locus coeruleus in the generation of pathological anxiety

Brain and Neuroscience Advances, Год журнала: 2020, Номер 4, С. 239821282093032 - 239821282093032

Опубликована: Янв. 1, 2020

This review aims to synthesise a large pre-clinical and clinical literature related hypothesised role of the locus coeruleus norepinephrine system in responses acute chronic threat, as well emergence pathological anxiety. The has widespread projections throughout central nervous system, which act globally modulate arousal states adaptive behavior, crucially positioned play significant modulating both ascending visceral descending cortical neurocognitive information. In response threat or stressor, coeruleus–norepinephrine modulates arousal, alerting orienting functions can have powerful effect on regulation multiple memory systems. Chronic stress leads amplification reactivity subsequent stressors, is coupled with anxiety-like behaviors rodents. While direct vivo evidence for dysfunction humans anxiety remains limited, recent advances high-resolution 7-T magnetic resonance imaging computational modeling approaches are starting provide new insights into characteristics.

Язык: Английский

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Neuromodulation in circuits of aversive emotional learning

Nature Neuroscience, Год журнала: 2019, Номер 22(10), С. 1586 - 1597

Опубликована: Сен. 24, 2019

Язык: Английский

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