A Checking Model of Obsessive-Compulsive Disorder Based on the Hypothalamic Defensive System Against a Potential Threat DOI Open Access

Noriko Horii‐Hayashi,

Kazuya Masuda,

Taika Kato

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Nov. 2, 2022

ABSTRACT BACKGROUND Obsessive-compulsive disorder (OCD) is a psychiatric characterized by obsessive thoughts and compulsive behavior. While some theories imply that OCD patients have cognitive biases dysfunctional motivation regarding potential threat, these views are not adequately supported neurological evidence. Hypothalamic perifornical (PeF) urocortin-3 (UCN3) neurons involved in defensive responses to the activation of mice induces repetitive excessive checking burying novel objects. In this study, we evaluated hypothesis which PeF UCN3 activated can serve as an model. METHODS were chemogenetically with clozapine-N oxide (CNO) Ucn3-Cre mice. Marble-burying activity, repetitive/stereotypic behaviors homecage, object measured OCD-like behaviors. The effects clinically used drugs for treating on evaluated. effect CNO neural activity cortico-striato-thalamo-cortical loop (which regarded circuit) was assessed c-Fos immunolabeling. RESULTS increased marble-burying evoked homecage-specific probably aimed seal entrances, induced These suppressed selective serotonin-reuptake inhibitors but diazepam. loop. CONCLUSIONS results indicated whose model OCD, particularly This supports concerning role threats pathophysiology OCD.

Language: Английский

Dorsolateral septum GLP-1R neurons regulate feeding via lateral hypothalamic projections DOI Creative Commons
Yi Lu, Le Wang, Fang Luo

et al.

Molecular Metabolism, Journal Year: 2024, Volume and Issue: 85, P. 101960 - 101960

Published: May 17, 2024

Although glucagon-like peptide 1 (GLP-1) is known to regulate feeding, the central mechanisms contributing this function remain enigmatic. Here, we aim test role of neurons expressing GLP-1 receptors (GLP-1R) in dorsolateral septum (dLS; dLSGLP-1R) that project lateral hypothalamic area (LHA) on food intake and determine relationship with feeding regulation. Using chemogenetic manipulations, assessed how activation or inhibition dLSGLP-1R affected Glp1r-ires-Cre mice. Then, used channelrhodopsin-assisted circuit mapping, chemogenetics, electrophysiological recordings identify assess pathway from →LHA projections regulating intake. Chemogenetic increases LHA a major downstream target neurons. The dLSGLP-1R→LHA are GABAergic, also promotes While modestly decreases intake, optogenetic stimulation projection terminals rapidly suppressed behavior. Finally, demonstrate GLP-1R agonist, Exendin 4 enhances GABA release. Together, these results dLS-GLP-1R inhibitory can behavior, which might serve as potential therapeutic for treatment eating disorders obesity.

Language: Английский

Citations

9
Elevated IL-22 as a result of stress-induced gut leakage suppresses septal neuron activation to ameliorate anxiety-like behavior DOI Creative Commons

Mengyu Xia,

Junmei Lü, J. Lan

et al.

Immunity, Journal Year: 2024, Volume and Issue: 58(1), P. 218 - 231.e12

Published: Dec. 6, 2024

Language: Английский

Citations

4
Lateral septum as a possible regulatory center of maternal behaviors DOI Creative Commons

Gina Puska,

Vivien Szendi,

Árpád Dobolyi

et al.

Neuroscience & Biobehavioral Reviews, Journal Year: 2024, Volume and Issue: 161, P. 105683 - 105683

Published: April 21, 2024

The lateral septum (LS) is involved in controlling anxiety, aggression, feeding, and other motivated behaviors. Lesion studies have also implicated the LS various forms of caring Recently, novel experimental tools provided a more detailed insight into function LS, including specific role distinct cell types their neuronal connections behavioral regulations, which participates. This article discusses regulation different maternal alterations using distributions established hormones such as prolactin, estrogens, neuropeptide oxytocin. It considers distribution neurons activated mothers response to pups activities, well gene expressional LS. Finally, this paper proposes further research directions keep up with rapidly developing knowledge on control brain regions.

Language: Английский

Citations

3
A projection from the medial prefrontal cortex to the lateral septum modulates coping behavior on the shock-probe test DOI
Jing Liu,

Kayla M Tabisola,

David A. Morilak

et al.

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

Published: Feb. 27, 2025

Language: Английский

Citations

0
Astrocytes in Rodent Anxiety-Related Behavior: Role of Calcium and Beyond DOI Open Access

Marta Gómez‐Gonzalo

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2774 - 2774

Published: March 19, 2025

Anxiety is a physiological, emotional response that anticipates distal threats. When kept under control, anxiety beneficial response, helping animals to maintain heightened attention in environments with potential dangers. However, an overestimation of threats can lead excessive expression that, humans, may evolve into disorders. Pharmacological treatments show variable efficacy among patients, highlighting the need for more efforts better understand pathogenesis Mounting evidence suggests astrocytes, type glial cells, are active partners neurons brain circuits and regulation behaviors both physiological pathological conditions. In this review, I summarize current literature on role astrocytes from different regions modulating anxious states, goal exploring novel cerebral mechanisms identify innovative therapeutic targets treatment

Language: Английский

Citations

0
Electome network factors: Capturing emotional brain networks related to health and disease DOI Creative Commons
Kathryn K. Walder-Christensen, Karim Abdelaal,

Hunter Klein

et al.

Cell Reports Methods, Journal Year: 2024, Volume and Issue: 4(1), P. 100691 - 100691

Published: Jan. 1, 2024

Therapeutic development for mental disorders has been slow despite the high worldwide prevalence of illness. Unfortunately, cellular and circuit insights into disease etiology have largely failed to generalize across individuals that carry same diagnosis, reflecting an unmet need identify convergent mechanisms would facilitate optimal treatment. Here, we discuss how mesoscale networks can encode affect other cognitive processes. These be discovered through electrical functional connectome (electome) analysis, a method built upon explainable machine learning models analyzing interpreting brain-wide signals in behavioral context. We also outline best practices identifying these generalizable, interpretable, biologically relevant networks. Looking forward, translational electome analysis span species various moods, processes, or brain states, supporting medicine. Thus, argue provides potential biomarkers developing next-generation therapeutics exhibit efficacy heterogeneous disorders.

Language: Английский

Citations

3
5-HT1A receptors within the intermediate lateral septum modulate stress vulnerability in male mice DOI
Jie Zhou,

Jiao-Wen Wu,

Bailin Song

et al.

Progress in Neuro-Psychopharmacology and Biological Psychiatry, Journal Year: 2024, Volume and Issue: 132, P. 110966 - 110966

Published: Feb. 13, 2024

Language: Английский

Citations

2
A dorsal hippocampus-prodynorphinergic dorsolateral septum-to-lateral hypothalamus circuit mediates contextual gating of feeding DOI Creative Commons
Travis D. Goode, Jason Bondoc Alipio, B Antoine

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 6, 2024

SUMMARY Adaptive regulation of feeding depends on linkage internal states and food outcomes with contextual cues. Human brain imaging has identified dysregulation a hippocampal-lateral hypothalamic area (LHA) network in binge eating, but mechanistic instantiation underlying cell-types circuitry is lacking. Here, we identify an evolutionary conserved discrete Prodynorphin ( Pdyn )-expressing subpopulation Somatostatin Sst inhibitory neurons the dorsolateral septum (DLS) that receives primarily dorsal, not ventral, hippocampal inputs. DLS( ) inhibit LHA GABAergic confer context- state-dependent calibration feeding. Viral deletion DLS mimicked effects seen optogenetic silencing INs, suggesting potential role for DYNORPHIN-KAPPA OPIOID RECEPTOR signaling food-seeking. Together, our findings illustrate how dorsal hippocampus evolved to recruit ancient circuit module through link information consumption. HIGHLIGHTS receive dense input from ventral Silencing hippocampus-DLS( )-LHA nodes abolishes context-conditioned necessary

Language: Английский

Citations

1
Sugar Beverage Habitation Relieves Chronic Stress-Induced Anxiety-like Behavior but Elicits Compulsive Eating Phenotype via vLSGAD2 Neurons DOI Open Access
Dan Liu, Haohao Hu, Yuchuan Hong

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 24(1), P. 661 - 661

Published: Dec. 30, 2022

Chronically stressed individuals are reported to overconsume tasty, palatable foods like sucrose blunt the psychological and physiological impacts of stress. Negative consequences high-sugar intake on feeding behavior include increased metabolic disease burdens obesity. However, neural basis underlying long-term intake-induced overeating during stress is not fully understood. To investigate this question, we used two-bottle choice paradigm in mice exposed chronic unpredictable mild stressors (CUMS) that mimic those daily life stressors. After 21 days CUMS paralleled by consecutive drinking, explored anxiety-like using elevated plus maze open field tests. The normal water-drinking displayed more anxiety than sucrose-drinking mice. Although anxiolytic effects, exhibited binge eating (chow) a compulsive phenotype. also showed significant body-weight gain compared control We further found c-Fos expression was significantly ventral part lateral septum (vLS) sucrose-treated after eating. Pharmacogenetic activation vLS glutamate decarboxylase 2(GAD2) neurons maintained plain chow but induced phenotype naïve GAD2-Cre when challenged flash stimulus, mimicking negative excessive drinking Further, pharmacogenetic vLSGAD2 aggravated did alter basal level ones. These findings indicate GABAergic within may be potential intervention target for comorbid disorders

Language: Английский

Citations

5
Dopamine D2 receptor within the intermediate region of the lateral septum modulate social hierarchy in male mice DOI
Bailin Song, Jie Zhou, Yi Jiang

et al.

Neuropharmacology, Journal Year: 2023, Volume and Issue: 241, P. 109735 - 109735

Published: Oct. 1, 2023

Language: Английский

Citations

2