Synaptic and transcriptomic features of cortical and amygdala pyramidal neurons predict inefficient fear extinction DOI Creative Commons
Daniela Laricchiuta, Juliette Gimenez, Giuseppe Sciamanna

et al.

Cell Reports, Journal Year: 2023, Volume and Issue: 42(9), P. 113066 - 113066

Published: Aug. 31, 2023

Fear-related disorders arise from inefficient fear extinction and have immeasurable social economic costs. Here, we characterize mouse phenotypes that spontaneously show fear-independent behavioral traits predicting adaptive or maladaptive extinction. We find that, already before conditioning, specific morphological, electrophysiological, transcriptomic patterns of cortical amygdala pyramidal neurons predispose to fear-related disorders. Finally, by using an optogenetic approach, the possibility rescue activating infralimbic impair prelimbic neurons.

Language: Английский

Cholecystokinin B receptor antagonists for the treatment of depression via blocking long-term potentiation in the basolateral amygdala DOI
Xu Zhang, Muhammad Asim, Wei Fang

et al.

Molecular Psychiatry, Journal Year: 2023, Volume and Issue: 28(8), P. 3459 - 3474

Published: June 26, 2023

Language: Английский

Citations

13
Memory Trace for Fear Extinction: Fragile yet Reinforceable DOI Creative Commons
Ying Liu, Shuai Ye,

Xin-Ni Li

et al.

Neuroscience Bulletin, Journal Year: 2023, Volume and Issue: 40(6), P. 777 - 794

Published: Oct. 9, 2023

Fear extinction is a biological process in which learned fear behavior diminishes without anticipated reinforcement, allowing the organism to re-adapt ever-changing situations. Based on behavioral hypothesis that new learning and forms an memory, this memory more readily forgettable than original memory. The brain's cellular synaptic traces underpinning inherently fragile yet reinforceable remain unclear. Intriguing questions are about whereabouts of engram neurons emerged during how they constitute dynamically evolving functional construct works concert store express In review, we discuss recent advances circuits their neural connectivity plasticity for extinction, aiming establish conceptual framework understanding dynamic competition between memories adaptive control conditioned responses.

Language: Английский

Citations

11
Calcium levels in ASER neurons determine behavioral valence by engaging distinct neuronal circuits in C. elegans DOI Creative Commons
Weikang Xue,

Yuan‐Hua Chen,

Ziyi Lei

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 20, 2025

The valence of stimuli is shaped by various factors, including environmental cues, internal states, genetic variability, and past experience. However, the mechanisms behind this flexibility remain elusive. In nematode C. elegans, we found that ethanol, an olfactory stimulus, can elicit opposite chemotaxis responses - attraction vs. aversion depending on NaCl concentration, demonstrating role factors in altering valence. Remarkably, a single chemosensory neuron, ASER, orchestrate bidirectional ethanol integrating information from both into its neuronal activity dynamics. Specifically, different calcium dynamics ASER neuron differentially activate signaling molecule CMK-1, thereby engaging downstream interneurons leading to directions. Consistently, optogenetic manipulations reverse directions, Our findings reveal mechanism which integrates multisensory inputs determine context-dependent behavioral valence, contributing our current understanding encoding.

Language: Английский

Citations

0
Regulation of PVT‐CeA Circuit in Deoxynivalenol‐Induced Anorexia and Aversive‐Like Emotions DOI Creative Commons
Liu‐Nan Yang,

Mingmeng Tang,

Andreas K. Nüssler

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 28, 2025

Abstract Neuronal plasticity in the central amygdala (CeA) is essential for modulating feeding behaviors and emotional responses, potentially influencing reactions to Deoxynivalenol (DON). Acute oral administration of DON elicits a dose‐responsive reduction food intake, accompanied by pronounced alterations locomotor activity frequency. This study investigates circuitry adaptations that mediate DON's effects on feeding, targeting GABA neurons CeA. Following exposure DON, an increase connectivity between paraventricular nucleus thalamus (PVT) CeA observed, suggesting involvement this pathway adverse states. Chemogenetic optogenetic manipulations resulted substantial mice's overall activity. These findings suggest are involved DON‐induced anorexia aversive‐like responses. Additionally, SCN10A antagonist (A‐803467) effectively mitigated emotions, highlighting pivotal role PVT‐CeA circuit regulating physiological impacts DON. have significant implications public health clinical interventions, offering potential therapeutic strategies mitigate human health.

Language: Английский

Citations

0
Dynorphin modulates reward-seeking actions through a pallido-amygdala cholinergic circuit DOI
Qingtao Sun, Mingzhe Liu, Wuqiang Guan

et al.

Neuron, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

Citations

0
Serotonin and neurotensin inputs in the vCA1 dictate opposing social valence DOI Creative Commons

Julia M Zorab,

Huanhuan Li, Richa Awasthi

et al.

Nature, Journal Year: 2025, Volume and Issue: unknown

Published: April 30, 2025

The ability to evaluate valence of a social agent based on experience is essential for an animal's survival in its group1. Although hippocampal circuits have been implicated distinguishing novel and familiar conspecifics2-7, it remains unclear how constructed the basis history what mechanisms underlie heightened versatility dynamic relationships. Here we demonstrate that ventral (v)CA1 integrates serotonin (5-HT) inputs from dorsal raphe neurotensin paraventricular nucleus thalamus (PVT) determine positive or negative conspecific representations. Specifically, during appetitive interaction 5-HT released into vCA1 disinhibits pyramidal neurons through 5-HT1B receptors, whereas aversive potentiates directly NTR1s. Optogenetic silencing PVT impairs valence, respectively, excitation flexibly switches assignment. These results show rewarding experiences are linked identity converging signals instruct opposing represent synaptic switch flexible computation.

Language: Английский

Citations

0
Current and emerging methods for probing neuropeptide transmission DOI
Tongrui Qian, Huan Wang, Xiju Xia

et al.

Current Opinion in Neurobiology, Journal Year: 2023, Volume and Issue: 81, P. 102751 - 102751

Published: July 22, 2023

Language: Английский

Citations

10
Neurotensin and Alcohol Use Disorders: Towards a Pharmacological Treatment DOI Open Access
Francisco D. Rodríguez, Manuel Lisardo Sánchez, Rafael Coveñas

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(10), P. 8656 - 8656

Published: May 12, 2023

Harmful alcohol use is responsible for a group of disorders collectively named (AUDs), according to the DSM-5 classification. The damage induced by depends on amount, time, and consumption patterns (continuous heavy episodic drinking). It affects individual global well-being social familial environments with variable impact. Alcohol addiction manifests different degrees organ mental health detriment individual, exhibiting two main traits: compulsive drinking negative emotional states occurring at withdrawal, frequently causing relapse episodes. Numerous living conditions, including concomitant other psychoactive substances, lie in complexity AUD. Ethanol its metabolites directly impact tissues may cause local or alter homeostasis brain neurotransmission, immunity scaffolding, cell repair biochemical pathways. Brain modulator neurotransmitter-assembled neurocircuitries govern reward, reinforcement, interaction, behaviors an intertwined manner. Experimental evidence supports participation neurotensin (NT) preclinical models addiction. For example, NT neurons central nucleus amygdala projecting parabrachial strengthen preference. In addition, levels frontal cortex were found be lower rats bred prefer water free alcohol–water choice compared wild-type animals. receptors 1 2 seem involved effects several knockout mice. This review aims present updated picture role systems possible nonpeptide ligands modulating activity system, applied experimental animal harmful behavior mimicking leading ruin humans.

Language: Английский

Citations

9
A neural mechanism for learning from delayed postingestive feedback DOI Creative Commons
Christopher A Zimmerman,

Scott S. Bolkan,

Alejandro Pan-Vazquez

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 10, 2023

Animals learn the value of foods based on their postingestive effects and thereby develop aversions to that are toxic

Language: Английский

Citations

9
An Honest Reckoning With the Amygdala and Mental Illness DOI
Andrew S. Fox, Alexander J. Shackman

American Journal of Psychiatry, Journal Year: 2024, Volume and Issue: 181(12), P. 1059 - 1075

Published: Dec. 1, 2024

Anxiety disorders are a leading source of human misery, morbidity, and premature mortality. Existing treatments far from curative for many, underscoring the need to clarify underlying neural mechanisms. Although many brain regions contribute, amygdala has received most intense scientific attention. Over past several decades, this scrutiny yielded detailed understanding function, but it failed produce new clinical assays, biomarkers, or cures. Rising urgent public health challenge demands an honest reckoning with functional-neuroanatomical complexity shift theories anchored on "the amygdala" models centered specific nuclei cell types. This review begins by examining evidence studies rodents, monkeys, humans "canonical model," idea that plays central role in fear- anxiety-related states, traits, disorders. Next, authors selectively highlight work indicating canonical model, while true, is overly simplistic fails adequately capture actual state evidentiary record, breadth amygdala-associated functions illnesses, amygdala's functional architecture. The describe implications these facts basic neuroimaging research. concludes some general recommendations grappling accelerating efforts understand more effectively treat amygdala-related psychopathology.

Language: Английский

Citations

3