Mesoscale brain-wide fluctuation analysis: revealing ketamine’s rapid antidepressant across multiple brain regions

Translational Psychiatry, Год журнала: 2025, Номер 15(1)

Опубликована: Апрель 19, 2025

Depression has been linked to cortico-limbic brain regions, and ketamine is known for its rapid antidepressant effects. However, how these regions encode depression collaboratively regulates exert prompt effects through mesoscale brain-wide fluctuations remain elusive. In this study, we used a multidisciplinary approach, including multi-region in vivo recordings mice, chronic social defeat stress (CSDS), machine learning, construct Mesoscale Brain-Wide Fluctuation Analysis platform (MBFA-platform). This analyzes the of multiple from perspective local field potential oscillations network dynamics. The decoder results demonstrate that our MBFA can accurately classify Control/CSDS ketamine/saline-treated groups based on neural oscillation activities among eight regions. We found multiple-region LFPs patterns are disrupted CSDS-induced avoidance, with basolateral amygdala playing key role. Ketamine primarily exerts compensatory dynamics, contributing effect. These findings highlight as an interdisciplinary tool revealing underlying complex emotional pathologies, providing insights into etiology psychiatry. Furthermore, platform's evaluation capabilities present novel approach psychiatric therapeutic interventions.

Язык: Английский

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(R)-ketamine induces mGlu5 receptor-dependent antidepressant-like effects in the chronic unpredictable mild stress model of depression in mice

Psychopharmacology, Год журнала: 2025, Номер unknown

Опубликована: Май 8, 2025

Abstract Rationale (S) -Ketamine, which is used to treat depression, has significant undesirable effects and potential for abuse. A safe alternative -ketamine (R) -ketamine. The relationship between the mGlu 5 receptor unknown, although screening tests indicate possibility of potentiation antidepressant effect by negative allosteric modulator (NAM). Objectives We aimed investigate whether antidepressant-like receptor-dependent. Specifically, we investigated enhancing using partial NAM, 2-(2-(3-methoxyphenyl)ethynyl)-5-methylpyridine (M-5MPEP), in a chronic unpredictable mild stress (CUMS) model depression mice. Methods on availability mouse brain was an autoradiographic method. Animal behaviors reflecting anhedonia, apathy, helplessness were analyzed study rapid sustained combined administration M-5MPEP. Hippocampal protein levels measured via Western blotting. Results -Ketamine altered several regions. Importantly, hippocampus, reversed CUMS-induced effects. Behavioral studies revealed that M-5MPEP enhanced effectiveness subeffective dose This drug combination effectively reduced apathy- anhedonia-like behavior symptoms. Changes hippocampal eukaryotic elongation factor2 (eEF2) tropomyosin kinase B (TrkB) accompanied these Conclusions weakening function hippocampus appears be related effect, coadministration M-5MPEP, might increase its activity.

Язык: Английский

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Functional and Molecular Changes in the Prefrontal Cortex of the Chronic Mild Stress Rat Model of Depression and Modulation by Acute Ketamine

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(13), С. 10814 - 10814

Опубликована: Июнь 28, 2023

Stress is a primary risk factor in the onset of neuropsychiatric disorders, including major depressive disorder (MDD). We have previously used chronic mild stress (CMS) model depression male rats to show that CMS induces morphological, functional, and molecular changes hippocampus vulnerable animals, majority which were recovered using acute subanesthetic ketamine just 24 h. Here, we focused our attention on medial prefrontal cortex (mPFC), brain area regulating emotional cognitive functions, asked whether vulnerability/resilience antidepressant effects associated with functional mPFC rats. found most alterations induced by selectively observed stress-vulnerable animals rescued ketamine, while others only resilient or treatment. Importantly, few these modifications also demonstrated hippocampus, are specific mPFC. Overall, results suggest rescues brain-area-specific glutamatergic stress.

Язык: Английский

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Locus Coeruleus‐Dorsolateral Septum Projections Modulate Depression‐Like Behaviors via BDNF But Not Norepinephrine

Advanced Science, Год журнала: 2023, Номер 11(10)

Опубликована: Дек. 28, 2023

Abstract Locus coeruleus (LC) dysfunction is involved in the pathophysiology of depression; however, neural circuits and specific molecular mechanisms responsible for this remain unclear. Here, it shown that activation tyrosine hydroxylase (TH) neurons LC alleviates depression‐like behaviors susceptible mice. The dorsolateral septum (dLS) most physiologically relevant output from under stress. Stimulation TH ‐dLS SST innervation with optogenetic chemogenetic tools bidirectionally can regulate both male female Mechanistically, found brain‐derived neurotrophic factor (BDNF), but not norepinephrine, required circuit to produce antidepressant‐like effects. Genetic overexpression BDNF or supplementation protein dLS sufficient Furthermore, viral knockdown abolishes effect ketamine, fluoxetine. Collectively, these findings underscore notable role pathway depression via BDNF‐TrkB signaling.

Язык: Английский

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Distinct synaptic mechanisms drive the behavioral response to acute stress and rapid correction by ketamine

Neuropsychopharmacology, Год журнала: 2024, Номер 49(12), С. 1916 - 1924

Опубликована: Июль 1, 2024

Prevailing hypotheses on the mechanisms of antidepressant action posit that antidepressants directly counteract deficiencies in major neurotransmitter signaling systems underlie depression. The rapidly acting ketamine has been postulated to correct excess glutamatergic via antagonism leading rescue neuronal structural deficits and reversal behavioral symptoms. We studied this premise using systemic administration acetylcholinesterase inhibitor physostigmine, which shown elicit a shorter-term period depressed mood humans cholinergic mechanisms. observed physostigmine induces acute stress tandem with long term depression glutamate release hippocampus mice. However, acts re-establish synaptic efficacy postsynaptic behaviorally masks reduction passive coping induced by physostigmine. These results underscore divergence underlying changes highlight how distinct may neuropsychiatric disorders versus their treatment.

Язык: Английский

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