A nociceptive neuronal ensemble in the dorsomedial prefrontal cortex underlies pain chronicity DOI Creative Commons
Xuetao Qi, Kun Cui, Yu Zhang

et al.

Cell Reports, Journal Year: 2022, Volume and Issue: 41(11), P. 111833 - 111833

Published: Dec. 1, 2022

Pain chronicity involves unpleasant experience in both somatosensory and affective aspects, accompanied with the prefrontal cortex (PFC) neuroplastic alterations. However, whether specific PFC neuronal ensembles underlie pain remains elusive. Here we identify a nociceptive ensemble dorsomedial (dmPFC), which shows prominent reactivity to stimuli. We observed that this distinct molecular characteristics is densely connected pain-related regions including basolateral amygdala (BLA) lateral parabrachial nuclei (LPB). Prolonged chemogenetic activation of ensemble, but not randomly transfected subset dmPFC neurons, induces chronic pain-like behaviors normal mice. By contrast, silencing neurons relieves hypersensitivity anxiety mice inflammatory pain. These results suggest presence processing information regulating chronicity.

Language: Английский

Restoration of excitation/inhibition balance enhances neuronal signal-to-noise ratio and rescues social deficits in autism-associatedScn2a-deficiency DOI Creative Commons
Jingliang Zhang, Muriel Eaton, Xiaoling Chen

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 5, 2025

Social behavior is critical for survival and adaptation, which profoundly disrupted in autism spectrum disorders (ASD). withdrawal due to information overload was often described ASD, it suspected that increased basal noise, i.e., excessive background neuronal activities the brain could be a disease mechanism. However, experimental test of this hypothesis limited. Loss-of-function mutations (deficiency) SCN2A , encodes voltage-gated sodium channel Na V 1.2, have been revealed as leading monogenic cause profound ASD. Here, we Scn2a deficiency results robust multifaceted social impairments mice. -deficient neurons displayed an excitation-inhibition (E/I) ratio, contributing elevated noise diminished signal-to-noise ratio (SNR) during interactions. Notably, restoration expression adulthood able rescue both SNR deficits. By balancing E/I reducing firing, FDA-approved GABA A receptor-positive allosteric modulator improves sociability mice normalizes translationally relevant human organoids carrying autism-associated nonsense mutation. Collectively, our findings role 1.2 regulation behaviors, identified molecular, cellular, circuitry mechanisms underlying -associated disorders. leads pronounced deficits overall enhanced activity, impaired ratio. Both are reversible through adulthood. Targeted striatum-projecting rescues impairments. transmission reduced mouse organoid models deficiency, acute systemic administration modulators restores sociability. Graphical abstract: Severe predominate decrease with SNR, adult 1.2-deficient

Language: Английский

Citations

1
Cell type–differential modulation of prefrontal cortical GABAergic interneurons on low gamma rhythm and social interaction DOI Creative Commons
Ling Liu, Haifeng Xu, Jun Wang

et al.

Science Advances, Journal Year: 2020, Volume and Issue: 6(30)

Published: July 22, 2020

Prefrontal cortical PV INs and SST differentially regulate low gamma rhythms social interaction behavior.

Language: Английский

Citations

70
State-dependent encoding of exploratory behaviour in the amygdala DOI
María Sol Fustiñana, Tobias Eichlisberger, Tewis Bouwmeester

et al.

Nature, Journal Year: 2021, Volume and Issue: 592(7853), P. 267 - 271

Published: March 3, 2021

Language: Английский

Citations

52
Neural circuit pathology driven by Shank3 mutation disrupts social behaviors DOI Creative Commons
Sunwhi Kim,

Yong-Eun Kim,

Inuk Song

et al.

Cell Reports, Journal Year: 2022, Volume and Issue: 39(10), P. 110906 - 110906

Published: June 1, 2022

Dysfunctional sociability is a core symptom in autism spectrum disorder (ASD) that may arise from neural-network dysconnectivity between multiple brain regions. However, pathogenic mechanisms underlying social dysfunction are largely unknown. Here, we demonstrate circuit-selective mutation (ctMUT) of ASD-risk Shank3 gene within unidirectional projection the prefrontal cortex to basolateral amygdala alters spine morphology and excitatory-inhibitory balance circuit. ctMUT mice show reduced as well elevated neural activity its amplitude variability, which consistent with neuroimaging results human ASD patients. Moreover, circuit hyper-activity disrupts temporal correlation socially tuned neurons events interactions. Finally, optogenetic activation wild-type partially recapitulates mice, while inhibition rescues behavior. Collectively, these highlight circuit-level mechanism drives dysfunction.

Language: Английский

Citations

33
A nociceptive neuronal ensemble in the dorsomedial prefrontal cortex underlies pain chronicity DOI Creative Commons
Xuetao Qi, Kun Cui, Yu Zhang

et al.

Cell Reports, Journal Year: 2022, Volume and Issue: 41(11), P. 111833 - 111833

Published: Dec. 1, 2022

Pain chronicity involves unpleasant experience in both somatosensory and affective aspects, accompanied with the prefrontal cortex (PFC) neuroplastic alterations. However, whether specific PFC neuronal ensembles underlie pain remains elusive. Here we identify a nociceptive ensemble dorsomedial (dmPFC), which shows prominent reactivity to stimuli. We observed that this distinct molecular characteristics is densely connected pain-related regions including basolateral amygdala (BLA) lateral parabrachial nuclei (LPB). Prolonged chemogenetic activation of ensemble, but not randomly transfected subset dmPFC neurons, induces chronic pain-like behaviors normal mice. By contrast, silencing neurons relieves hypersensitivity anxiety mice inflammatory pain. These results suggest presence processing information regulating chronicity.

Language: Английский

Citations

33