Genetically identified amygdala–striatal circuits for valence-specific behaviors

Nature Neuroscience, Journal Year: 2021, Volume and Issue: 24(11), P. 1586 - 1600

Published: Oct. 18, 2021

Language: Английский

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Neurobiology of cannabinoid receptor signaling

Dialogues in Clinical Neuroscience, Journal Year: 2020, Volume and Issue: 22(3), P. 207 - 222

Published: Sept. 30, 2020

The endocannabinoid system (ECS) is a highly versatile signaling within the nervous system. Despite its widespread localization, functions context of distinct neural processes are very well discernable and specific. This remarkable, question remains as to how such specificity achieved. One key player in ECS cannabinoid type 1 receptor (CB1), G protein–coupled characterized by complexity cell-specific expression, cellular subcellular adaptable regulation intracellular cascades. CB1 receptors involved different synaptic plasticity brain's bioenergetics context-specific manner. CB2 also important several neurons, glial cells, immune cells brain. As polymorphisms components, external impacts stress metabolic challenges, can both lead dysregulated activity subsequently possible neuropsychiatric disorders, pharmacological intervention targeting promising therapeutic approach. Understanding neurobiology depth will aid optimal design interventions, minimizing unwanted side effects.

Language: Английский

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Nucleus Accumbens Cell Type- and Input-Specific Suppression of Unproductive Reward Seeking

Cell Reports, Journal Year: 2020, Volume and Issue: 30(11), P. 3729 - 3742.e3

Published: March 1, 2020

The nucleus accumbens (NAc) contributes to behavioral inhibition and compulsions, but circuit mechanisms are unclear. Recent evidence suggests that amygdala thalamic inputs exert opposing control over behavior, much like direct indirect pathway output neurons. Accordingly, opponent processes between these NAc or cell types may underlie efficient reward seeking. We assess the contributions of elements mouse operant behavior during recurring conditions when is not available. Although stimulation rewarding aversive, activity both elevated periods suppression, either cell-type selectively increases unproductive Amygdala also necessary for even though they support self-stimulation innervate different subregions. These data suggest seeking relies on complementary across rather than them.

Language: Английский

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CB1 Cannabinoid Receptor Signaling and Biased Signaling

Molecules, Journal Year: 2021, Volume and Issue: 26(17), P. 5413 - 5413

Published: Sept. 6, 2021

The CB1 cannabinoid receptor is a G-protein coupled highly expressed throughout the central nervous system that promising target for treatment of various disorders, including anxiety, pain, and neurodegeneration. Despite wide therapeutic potential CB1, development drug candidates hindered by adverse effects, rapid tolerance development, abuse potential. Ligands produce biased signaling—the preferential activation signaling transducer in detriment another—have been proposed as strategy to dissociate effects variety receptors. However, at poorly understood due lack strongly agonists. Here, we review studies have investigated profile classical agonists allosteric ligands, searching advantage different pathological states. Agonist antagonist bound structures mechanisms action modulators are used discuss putative molecular mechanism signaling. Current suggest binding sites on can be explored yield ligands favor or hinder conformational changes important

Language: Английский

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A neuropeptide regulates fighting behavior in Drosophila melanogaster

eLife, Journal Year: 2020, Volume and Issue: 9

Published: April 21, 2020

Aggressive behavior is regulated by various neuromodulators such as neuropeptides and biogenic amines. Here we found that the neuropeptide Drosulfakinin (Dsk) modulates aggression in Drosophila melanogaster. Knock-out of Dsk or receptor CCKLR-17D1 reduced aggression. Activation inactivation Dsk-expressing neurons increased decreased male aggressive behavior, respectively. Moreover, data from transsynaptic tracing, electrophysiology behavioral epistasis reveal function downstream a subset P1 (P1a-splitGAL4) to control fighting behavior. In addition, winners show calcium activity neurons. Conditional overexpression promotes social dominance, suggesting positive correlation between signaling winning effects. The mammalian ortholog CCK has been implicated mammal aggression, thus our work suggests conserved neuromodulatory system for modulation

Language: Английский

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Targeting presynaptic H3 heteroreceptor in nucleus accumbens to improve anxiety and obsessive-compulsive-like behaviors

Proceedings of the National Academy of Sciences, Journal Year: 2020, Volume and Issue: 117(50), P. 32155 - 32164

Published: Nov. 30, 2020

Significance Anxiety disorders and obsessive-compulsive disorder (OCD) are highly prevalent debilitating psychiatric commonly co-occurring in our stressful modern life. Yet the common effective therapeutic target is still unknown. Here we report that activation of histaminergic afferent system, particularly histamine H3 receptor, nucleus accumbens (NAc) core, a vital node limbic loop, inhibits glutamatergic synaptic transmission circuit from prelimbic prefrontal cortex (PrL) to NAc improves both anxiety- obsessive-compulsive-like behaviors induced by restraint stress. Our results define PrL–NAc involved modulated presynaptic heteroreceptor pave path for developing potential strategies clinical treatment anxiety OCD.

Language: Английский

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Reward and aversion processing by input-defined parallel nucleus accumbens circuits in mice

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Oct. 21, 2022

Abstract The nucleus accumbens (NAc) is critical in mediating reward seeking and also involved negative emotion processing, but the cellular circuitry mechanisms underlying such opposing behaviors remain elusive. Here, using recently developed AAV1-mediated anterograde transsynaptic tagging technique mice, we show that NAc neurons receiving basolateral amygdala inputs (NAc BLA ) promote positive reinforcement via disinhibiting dopamine ventral tegmental area (VTA). In contrast, paraventricular thalamic PVT innervate GABAergic lateral hypothalamus (LH) mediate aversion. Silencing synaptic output of impairs behavior, while silencing or →LH pathway abolishes aversive symptoms opiate withdrawal. Our results elucidate afferent-specific circuit architecture controlling

Language: Английский

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Neurotensin orchestrates valence assignment in the amygdala

Nature, Journal Year: 2022, Volume and Issue: 608(7923), P. 586 - 592

Published: July 20, 2022

Language: Английский

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Consolidating the Circuit Model for Addiction

Annual Review of Neuroscience, Journal Year: 2021, Volume and Issue: 44(1), P. 173 - 195

Published: March 5, 2021

Addiction is a disease characterized by compulsive drug seeking and consumption observed in 20–30% of users. An addicted individual will favor reward over natural rewards, despite major negative consequences. Mechanistic research on rodents modeling core components the has identified altered synaptic transmission as functional substrate pathological behavior. While initial version circuit model for addiction focused early adaptive behaviors all individuals, it fell short accounting stochastic nature transition to compulsion. The builds pharmacological effect common addictive drugs—an increase dopamine levels mesolimbic system. Here, we consolidate this integrating circuits underlying compulsion reinforcement. We discuss genetic epigenetic correlates vulnerability. Many recent data converge gain-of-function explanation remodeling, revealing blueprints novel therapies.

Language: Английский

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Distinct serotonergic pathways to the amygdala underlie separate behavioral features of anxiety

Nature Neuroscience, Journal Year: 2022, Volume and Issue: 25(12), P. 1651 - 1663

Published: Nov. 29, 2022

Language: Английский

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