The stressed synapse 2.0: pathophysiological mechanisms in stress-related neuropsychiatric disorders

Nature reviews. Neuroscience, Journal Year: 2021, Volume and Issue: 23(2), P. 86 - 103

Published: Dec. 10, 2021

Language: Английский

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Beyond the three-chamber test: toward a multimodal and objective assessment of social behavior in rodents

Molecular Autism, Journal Year: 2022, Volume and Issue: 13(1)

Published: Oct. 25, 2022

Abstract Main In recent years, substantial advances in social neuroscience have been realized, including the generation of numerous rodent models autism spectrum disorder. Still, it can be argued that those methods currently being used to analyze animal behavior create a bottleneck significantly slows down progress this field. Indeed, bulk research still relies on small number simple behavioral paradigms, results which are assessed without considering dynamics. Moreover, only few variables examined each paradigm, thus overlooking significant portion complexity characterizes interaction between two conspecifics, subsequently hindering our understanding neural mechanisms governing different aspects behavior. We further demonstrate these constraints by discussing most commonly paradigm for assessing behavior, three-chamber test. also point fact although emotions greatly influence human we lack reliable means emotional state animals during tasks. As such, discuss current evidence supporting existence pro-social and cognition models. suggest adequate analysis requires novel multimodal approach employs automated simultaneous measurements multiple physiological at high temporal resolution socially interacting animals. accordingly describe several computerized systems computational tools acquiring analyzing such measurements. Finally, address assess socio-emotional states elucidate intricacies so as attain deeper insight into brain mediate behaviors. Conclusions summary, combining with machine-learning algorithms will help define determine their dynamics various types tasks, enabling more thorough

Language: Английский

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Acetylcholine deficiency disrupts extratelencephalic projection neurons in the prefrontal cortex in a mouse model of Alzheimer’s disease

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

Published: Feb. 22, 2022

Abstract Short-term memory deficits have been associated with prefrontal cortex (PFC) dysfunction in Alzheimer’s disease (AD) and AD mouse models. Extratelencephalic projection (ET) neurons the PFC play a key role short-term working memory, but mechanism between ET neuronal impairment is not well understood. Here, using fiber photometry optogenetics, we found reduced neural activity medial (mPFC) of 5×FAD model led to object recognition (ORM) deficits. Activation mPFC mice rescued ORM impairment, inhibition wild type impaired expression. that project supramammillary nucleus were necessary for Viral tracing vivo recording revealed received fewer cholinergic inputs from basal forebrain mice. Furthermore, activation fibers mice, while acetylcholine deficiency response familiar objects. Taken together, our results behind

Language: Английский

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Beyond the neuron: Role of non-neuronal cells in stress disorders

Neuron, Journal Year: 2022, Volume and Issue: 110(7), P. 1116 - 1138

Published: Feb. 18, 2022

Language: Английский

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Molecular and cellular mechanisms for differential effects of chronic social isolation stress in males and females

Molecular Psychiatry, Journal Year: 2022, Volume and Issue: 27(7), P. 3056 - 3068

Published: April 21, 2022

Language: Английский

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Hyperexcitation of ovBNST CRF neurons during stress contributes to female-biased expression of anxiety-like avoidance behaviors

Science Advances, Journal Year: 2024, Volume and Issue: 10(19)

Published: May 10, 2024

Corticotropin releasing factor (CRF) network in the oval nucleus of bed nuclei stria terminalis (ovBNST) is generally indicated stress, but its role female-biased susceptibility to anxiety unknown. Here, we established a stress paradigm. We found that CRF release ovBNST during showed pattern, and neurons were more prone be hyperexcited female mice both vitro vivo studies. Moreover, optogenetic modulation exchange activation pattern between male could reverse their anxiety. Last, receptor type 1 (CRFR1) mediated CRF-induced excitation expression. Specific knockdown CRFR1 level or overexpression Therefore, identify CRFR1-mediated hyperexcitation encode

Language: Английский

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Dynamic influences on the neural encoding of social valence

Nature reviews. Neuroscience, Journal Year: 2022, Volume and Issue: 23(9), P. 535 - 550

Published: July 12, 2022

Language: Английский

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Striatal μ-opioid receptor activation triggers direct-pathway GABAergic plasticity and induces negative affect

Cell Reports, Journal Year: 2023, Volume and Issue: 42(2), P. 112089 - 112089

Published: Feb. 1, 2023

Highlights•Repeated morphine and fentanyl injections potentiate IPSCdMSN→GPh transmission•Repeated administration potentiates IPSCdMSN→SNc transmission•Fentanyl recruits striatal neurons that encode contextual memory•Striatal MOR+ drive withdrawal-induced negative affectSummaryWithdrawal from chronic opioid use often causes hypodopaminergic states affect, which may relapse. Direct-pathway medium spiny (dMSNs) in the patch compartment contain μ-opioid receptors (MORs). It remains unclear how exposure withdrawal impact these MOR-expressing dMSNs their outputs. Here, we report MOR activation acutely suppressed GABAergic striatopallidal transmission habenula-projecting globus pallidus neurons. Notably, repeated or potentiated this transmission. Furthermore, intravenous self-administration enhanced striatonigral reduced midbrain dopaminergic activity. Fentanyl-activated mediated memory retrieval required for conditioned place preference tests. Importantly, chemogenetic inhibition of rescued physical symptoms anxiety-like behaviors. These data suggest triggers plasticity to induce a state, promote emotions relapse.Graphical abstract

Language: Английский

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Diminished activity-dependent BDNF signaling differentially causes autism-like behavioral deficits in male and female mice

Frontiers in Psychiatry, Journal Year: 2023, Volume and Issue: 14

Published: May 3, 2023

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders with strong genetic heterogeneity and more prevalent in males than females. Recent human studies have identified multiple high-risk genes for ASD, which produce similar phenotypes, indicating that diverse factors converge to common molecular pathways. We others hypothesized activity-dependent neural signaling convergent pathway dysregulated ASD. However, the causal link between diminished ASD remains unclear. Brain-derived neurotrophic factor (BDNF) key molecule mediating signaling. therefore hypothesize BDNF could confer autism-like behavioral deficits. Here, we investigated effect on deficits by using mice knock-in methionine (Met) allele, has decreased release without altering basal level. Compared wild-type (WT) controls, similarly induced anxiety-like behaviors male female mice. Notably, differentially resulted social increased self-grooming mice, were severe Again, sexually dimorphic spatial memory observed +/Met but not Our study only reveals ASD-like deficits, also identifies previously underappreciated sex-specific These Met variant provide distinct mouse model studying cellular mechanisms underlying signaling,

Language: Английский

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CB1R dysfunction of inhibitory synapses in the ACC drives chronic social isolation stress-induced social impairments in male mice

Neuron, Journal Year: 2023, Volume and Issue: 112(3), P. 441 - 457.e6

Published: Nov. 21, 2023

Language: Английский

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