Mapping thalamic-anterior cingulate monosynaptic inputs in adult mice DOI Creative Commons

Man Xue,

Wantong Shi,

Si-Bo Zhou

et al.

Molecular Pain, Journal Year: 2022, Volume and Issue: 18

Published: March 4, 2022

The anterior cingulate cortex (ACC) is located in the frontal part of cortex, and plays important roles pain perception emotion. thalamocortical pathway major sensory input to ACC. Previous studies have show that several different thalamic nuclei receive projection fibers from spinothalamic tract, turn send efferents ACC by using neural tracers optical imaging methods. Most these were performed monkeys, cats, rats, few reported systematically adult mice. Adult mice, especially genetically modified provided molecular synaptic mechanisms for cortical plasticity modulation In present study, we utilized rabies virus-based retrograde tracing system map thalamic-anterior monosynaptic inputs We also combined with a new high-throughput VISoR technique generate three-dimensional whole-brain reconstruction, thalamus. found neurons received direct projections sub-nuclei thalamus, including anterior, ventral, medial, lateral, midline, intralaminar nuclei. These findings provide key anatomic evidences connection between thalamus

Language: Английский

Corticotropin-releasing hormone neurons control trigeminal neuralgia-induced anxiodepression via a hippocampus-to-prefrontal circuit DOI Creative Commons

Su‐Su Lv,

Xue‐Jing Lv,

Yaqi Cai

et al.

Science Advances, Journal Year: 2024, Volume and Issue: 10(3)

Published: Jan. 19, 2024

Anxiety and depression are frequently observed in patients suffering from trigeminal neuralgia (TN), but neural circuits mechanisms underlying this association poorly understood. Here, we identified a dedicated circuit the ventral hippocampus (vHPC) to medial prefrontal cortex (mPFC) that mediates TN-related anxiodepression. We found TN caused an increase excitatory synaptic transmission vHPC CaMK2A neurons mPFC inhibitory marked by expression of corticotropin-releasing hormone (CRH). Activation CRH + subsequently led feed-forward inhibition layer V pyramidal via activation receptor 1 (CRHR1). Inhibition -mPFC ameliorated TN-induced anxiodepression, whereas activating pathway sufficiently produced anxiodepressive-like behaviors. Thus, our studies driving pain-related anxiodepression molecular target for treating psychiatric disorders.

Language: Английский

Citations

11
The thalamic reticular nucleus orchestrates social memory DOI Creative Commons

Feidi Wang,

Huan Sun,

Mingyue Chen

et al.

Neuron, Journal Year: 2024, Volume and Issue: 112(14), P. 2368 - 2385.e11

Published: May 2, 2024

Social memory has been developed in humans and other animals to recognize familiar conspecifics is essential for their survival reproduction. Here, we demonstrated that parvalbumin-positive neurons the sensory thalamic reticular nucleus (sTRN

Language: Английский

Citations

10
Preclinical Insights into the Role of Kir4.1 in Chronic Pain and Depression: Mechanisms and Therapeutic Potential DOI Creative Commons

Tingfeng Zha,

Xinyi Fang,

Jiamin Wan

et al.

Biomolecules, Journal Year: 2025, Volume and Issue: 15(2), P. 165 - 165

Published: Jan. 23, 2025

Chronic pain and mental health disorders, such as depression anxiety, frequently co-occur share underlying mechanisms involving neuronal excitability synaptic transmission. The inwardly rectifying potassium channel 4.1 (Kir4.1), predominantly expressed in glial cells, is crucial for maintaining extracellular glutamate homeostasis. Dysregulation of Kir4.1 leads to altered activity, contributing both chronic disorders. In pain, downregulation impairs buffering clearance, increasing enhancing signaling through peripheral central sensitization. impaired function disrupts neurotrophic factor secretion neuroinflammatory pathways, leading mood disturbances. This review primarily summarizes findings from preclinical studies examine the relationship between pathogenesis discussing its molecular structure, expression patterns, functional roles. Furthermore, we explore therapeutic strategies targeting Kir4.1, including pharmacological modulators gene therapy approaches, emphasizing potential a novel target.

Language: Английский

Citations

1
Stress dynamically modulates neuronal autophagy to gate depression onset DOI Creative Commons
Liang Yang, Guo Chen, Zhi-Wei Zheng

et al.

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

Published: April 9, 2025

Chronic stress remodels brain homeostasis, in which persistent change leads to depressive disorders1. As a key modulator of homeostasis2, it remains elusive whether and how autophagy is engaged dynamics. Here we discover that acute activates, whereas chronic suppresses, mainly the lateral habenula (LHb). Systemic administration distinct antidepressant drugs similarly restores function LHb, suggesting LHb as common target. Genetic ablation neuronal promotes susceptibility, enhancing exerts rapid antidepressant-like effects. controls excitability, synaptic transmission plasticity by means on-demand degradation glutamate receptors. Collectively, this study shows causal role maintaining emotional homeostasis against stress. Disrupted implicated maladaptation stress, its reversal enhancers provides new strategy.

Language: Английский

Citations

1
TIAM1-mediated synaptic plasticity underlies comorbid depression–like and ketamine antidepressant–like actions in chronic pain DOI Creative Commons
Qin Ru, Yungang Lu, Ali Bin Saifullah

et al.

Journal of Clinical Investigation, Journal Year: 2022, Volume and Issue: 132(24)

Published: Dec. 14, 2022

Chronic pain often leads to depression, increasing patient suffering and worsening prognosis. While hyperactivity of the anterior cingulate cortex (ACC) appears be critically involved, molecular mechanisms underlying comorbid depressive symptoms in chronic remain elusive. T cell lymphoma invasion metastasis 1 (Tiam1) is a Rac1 guanine nucleotide exchange factor (GEF) that promotes dendrite, spine, synapse development during brain development. Here, we show Tiam1 orchestrates synaptic structural functional plasticity ACC neurons via actin cytoskeleton reorganization N-methyl-d-aspartate receptor (NMDAR) stabilization. This Tiam1-coordinated underpins drives pain–induced depressive-like behaviors. Notably, administration low-dose ketamine, an NMDAR antagonist emerging as promising treatment for induces sustained antidepressant-like effects mouse models by blocking Tiam1-mediated maladaptive neurons. Our results reveal critical pathophysiology behaviors ketamine.

Language: Английский

Citations

38
Up-regulation of microglial chemokine CXCL12 in anterior cingulate cortex mediates neuropathic pain in diabetic mice DOI

Zihua Song,

Xiang-Jie Song,

Chen-Ling Yang

et al.

Acta Pharmacologica Sinica, Journal Year: 2023, Volume and Issue: 44(7), P. 1337 - 1349

Published: Jan. 25, 2023

Language: Английский

Citations

22
The thalamic reticular nucleus-lateral habenula circuit regulates depressive-like behaviors in chronic stress and chronic pain DOI Creative Commons

Xin-Yue Wang,

Xiang Xu, Rui Chen

et al.

Cell Reports, Journal Year: 2023, Volume and Issue: 42(10), P. 113170 - 113170

Published: Sept. 21, 2023

Chronic stress and chronic pain are two major predisposing factors to trigger depression. Enhanced excitatory input the lateral habenula (LHb) has been implicated in pathophysiology of However, contribution inhibitory transmission remains unclear. Here, we dissect an projection from sensory thalamic reticular nucleus (sTRN) LHb, which is activated by acute aversive stimuli. restraint (CRS) weakens sTRN-LHb synaptic strength, this attenuation indispensable for CRS-induced LHb neural hyperactivity depression onset. Moreover, artificially inhibiting circuit induces depressive-like behaviors healthy mice, while enhancing relieves induced both pain. Intriguingly, neither neuropathic nor comorbid mechanical hypersensitivity affected pathway. Altogether, our study demonstrates establishing modulating depression, thus shedding light on potential therapeutic targets preventing or managing

Language: Английский

Citations

19
Development and Pharmacochemical Characterization Discover a Novel Brain-Permeable HDAC11-Selective Inhibitor with Therapeutic Potential by Regulating Neuroinflammation in Mice DOI
Ping Bai, Yan Liu, Liuyue Yang

et al.

Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 66(23), P. 16075 - 16090

Published: Nov. 16, 2023

Recent studies have shown that the epigenetic protein histone deacetylase 11 (HDAC11) is highly expressed in brain and critically modulates neuroimmune functions, making it a potential therapeutic target for neurological disorders. Herein, we report development of PB94, which novel HDAC11 inhibitor. PB94 exhibited potency selectivity against with IC50 = 108 nM >40-fold over other HDAC isoforms. Pharmacokinetic/pharmacodynamic evaluation indicated possesses promising drug-like properties. Additionally, was radiolabeled carbon-11 as [11C]PB94 positron emission tomography (PET), revealed significant uptake metabolic properties suitable drug live animals. Furthermore, demonstrated neuropathic pain associated upregulation pharmacological inhibition by ameliorated mouse model. Collectively, our findings support further selective inhibitor indications, including pain.

Language: Английский

Citations

17
Mediodorsal thalamus projection to medial prefrontal cortical mediates social defeat stress-induced depression-like behaviors DOI
Fang Li,

Xuefeng Zheng,

Hanjie Wang

et al.

Neuropsychopharmacology, Journal Year: 2024, Volume and Issue: 49(8), P. 1318 - 1329

Published: March 4, 2024

Language: Английский

Citations

7
Anterior cingulate cross-hemispheric inhibition via the claustrum resolves painful sensory conflict DOI Creative Commons
K. Koga, Kenta Kobayashi, Makoto Tsuda

et al.

Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)

Published: March 15, 2024

Abstract The anterior cingulate cortex (ACC) responds to noxious and innocuous sensory inputs, integrates them coordinate appropriate behavioral reactions. However, the role of projections ACC neurons subcortical areas their influence on processing are not fully investigated. Here, we identified that projecting contralateral claustrum (ACC →contraCLA ) preferentially respond mechanical stimulation. These responses were enhanced during attending behavior. Optogenetic activation silenced pyramidal in by recruiting local circuit fast-spiking interneuron via an excitatory relay CLA. This suppressed withdrawal behavior stimuli ipsilateral neurons. Chemogenetic silencing showed cross-hemispheric has important suppression nociceptive sensory-driven Our findings identify a cortical-subcortical-cortical arc allowing brain give attentional priority competing inputs.

Language: Английский

Citations

7