Linking Brain Circuitry and Neural Plasticity in Antidepressant Response: The mPFC-Reuniens-Hippocampus Pathway. DOI
Stefan Vestring, Maxime Veleanu, Jochen Weber

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: April 3, 2025

Abstract The pathophysiology of depression involves multiple biological processes, including circuit dysfunction and impaired neuroplasticity, yet an integrative view that links these processes remains elusive. Here, using a combination manipulation, electrophysiology, behavior, fiber photometry, we identify convergent for antidepressant response plasticity modulation. We demonstrate chemogenetic activation the infralimbic cortex (IL) is sufficient to exert rapid effects across behavioral domains in mouse model stress-induced exerts top-down control over hippocampal processing. show IL stimulation enhances structural plasticity, restores long-term potentiation improves state-dependent network dynamics hippocampus (HIP). identified nucleus reuniens (RE) as necessary mediator effects. Notably, RE inhibition blocks not only stimulation-induced but also therapeutic neuroplastic ketamine. Our findings functional → ventral HIP plays central role response, linking activity, depressive-like behaviors.

Language: Английский

Stress to inflammation and anhedonia: Mechanistic insights from preclinical and clinical models DOI Creative Commons
Chloe C. Boyle, Julienne E. Bower, Naomi I. Eisenberger

et al.

Neuroscience & Biobehavioral Reviews, Journal Year: 2023, Volume and Issue: 152, P. 105307 - 105307

Published: July 6, 2023

Language: Английский

Citations

18
Stress-induced anxiety-related behavior in mice is driven by enhanced excitability of ventral tegmental area GABA neurons DOI Creative Commons

Eric H. Mitten,

Anna Souders,

Ezequiel Marrón Fernández de Velasco

et al.

Frontiers in Behavioral Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: July 17, 2024

Introduction Stress and trauma are significant risk factors for many neuropsychiatric disorders diseases, including anxiety disorders. Stress-induced symptoms have been attributed to enhanced excitability in circuits controlling fear, anxiety, aversion. A growing body of evidence has implicated GABAergic neurons the ventral tegmental area (VTA) aversion processing affective behavior. Methods We used an unpredictable footshock (uFS) model, together with electrophysiological behavioral approaches, investigate role VTA GABA anxiety-related behavior mice. Results One day after a single uFS session, C57BL/6J mice exhibited elevated neuron excitability. The was correlated increased glutamatergic input reduction postsynaptic signaling mediated via B receptors. Chemogenetic activation sufficient increase stress-naïve In addition, chemogenetic inhibition suppressed exposed uFS. Discussion These data show that early substrate stress-induced suggest approaches mitigating may hold promise treatment provoked by stress trauma.

Language: Английский

Citations

5
Atypical antipsychotics antagonize GABAA receptors in the ventral tegmental area GABA neurons to relieve psychotic behaviors DOI
Chen Lu, Xiaona Zhu, Yifan Feng

et al.

Molecular Psychiatry, Journal Year: 2023, Volume and Issue: 28(5), P. 2107 - 2121

Published: Feb. 8, 2023

Language: Английский

Citations

12
Impact of stress on inhibitory neuronal circuits, our tribute to Bruce McEwen DOI Creative Commons
Marta Pérez-Rando, Héctor Carceller, Esther Castillo‐Gomez

et al.

Neurobiology of Stress, Journal Year: 2022, Volume and Issue: 19, P. 100460 - 100460

Published: May 13, 2022

This manuscript is dedicated to the memory of Bruce S. McEwen, commemorate impact he had on how we understand stress and neuronal plasticity, profound influence exerted our scientific careers. The focus this review stressors inhibitory circuits, particularly those limbic system, but also consider other regions affected by these adverse experiences. We revise effects acute chronic during different stages development lifespan, taking into account sex animals. first physiology neurons expression molecules related directly GABAergic neurotransmission, then specific interneuron subpopulations, parvalbumin somatostatin expressing cells. Then analyze structures plasticity neurons: polysialylated form neural cell adhesion molecule perineuronal nets. Finally, potential antidepressants or environmental manipulations revert circuits.

Language: Английский

Citations

17
Sex differences in chronic pain-induced mental disorders: Mechanisms of cerebral circuitry DOI Creative Commons

Zuqi Shen,

Wei Li,

Weiqi Chang

et al.

Frontiers in Molecular Neuroscience, Journal Year: 2023, Volume and Issue: 16

Published: Feb. 20, 2023

Mental disorders such as anxiety and depression induced by chronic pain are common in clinical practice, there significant sex differences their epidemiology. However, the circuit mechanism of this difference has not been fully studied, preclinical studies have traditionally excluded female rodents. Recently, oversight begun to be resolved including male rodents revealing neurobiological processes behind mental disorder features. This paper reviews structural functions involved injury perception advanced emotional cortex circuit. In addition, we also summarize latest breakthroughs insights into neuromodulation through endogenous dopamine, 5-hydroxytryptamine, GABAergic inhibition, norepinephrine, peptide pathways like oxytocin, well receptors. By comparing differences, hope identify new therapeutic targets offer safer more effective treatments.

Language: Английский

Citations

11
The mechanistic basis for the rapid antidepressant-like effects of ketamine: From neural circuits to molecular pathways DOI Creative Commons
Li Ren

Progress in Neuro-Psychopharmacology and Biological Psychiatry, Journal Year: 2023, Volume and Issue: 129, P. 110910 - 110910

Published: Dec. 6, 2023

Conventional antidepressants that target monoaminergic receptors require several weeks to be efficacious. This lag represents a significant problem in the currently available treatments for serious depression. Ketamine, acting as an N-methyl-d-aspartate receptor antagonist, was shown have rapid antidepressant-like effects, marking advancement study of mood disorders. However, side effects and adverse reactions limit its clinical use. Considering limitations ketamine, it is crucial further define network targets ketamine. The action ketamine antidepressant thought mediated by glutamate system. It believed synaptic plasticity essential antidepressant. Other mechanisms include involvement γ-aminobutyric acidergic (GABAergic), 5-HTergic systems, recent studies linked astrocytes ketamine's effects. interactions between these systems exert synergistic effect through neural circuits molecular mechanisms. Here, we discuss underlying work will help explain how are responsible rapidly aid discovery new therapeutic approaches major depressive disorder.

Language: Английский

Citations

11
Corticotropin-releasing factor and GABA in the ventral tegmental area modulate partner preference formation in male and female prairie voles (Microtus ochrogaster) DOI Creative Commons

Kyle R. Gossman,

Camryn Serra Lowe,

Adrianna Kirckof

et al.

Frontiers in Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: July 23, 2024

Introduction The mesolimbic reward system is associated with the promotion and rewarding benefits of social relationships. In socially monogamous prairie vole ( Microtus ochrogaster ), establishment a pair bond can be displayed by robust preference for breeding partner aggressive rejection unfamiliar conspecifics. Mesolimbic dopamine signaling influences bond-related behaviors within through transmission receptor activity in nucleus accumbens. However, only one experiment has examined how ventral tegmental area (VTA), region that produces much fore- mid-brain dopamine, regulates these behaviors. Specifically, inhibition either glutamate or GABA neurons VTA during brief courtship promoted formation male voles. heterogeneous structure contains GABA, as well receives variety projections including corticotropin-releasing factor (CRF) suggested to modulate release. Methods We used pharmacological manipulation examine CRF female we 3 h test, choice assess following an infused bicuculline 1 cohabitation muscimol CP154526, CRFR1 antagonist, 24 opposite-sex conspecific. Results Our study demonstrated bicuculline, A preference, whereas low-dose muscimol, agonist, inhibited both Conclusion This inputs into necessary

Language: Английский

Citations

4
Non-pharmacological therapeutic paradigms in stress-induced depression: from novel therapeutic perspective with focus on cell-based strategies DOI
Maryam Azarfarin,

M. Shahla,

Gisou Mohaddes

et al.

Acta Neuropsychiatrica, Journal Year: 2025, Volume and Issue: 37

Published: Jan. 1, 2025

Abstract Major depressive disorder (MDD) is considered a psychiatric and have relationship with stressful events. Although the common therapeutic approaches against MDD are diverse, large number of patients do not present an adequate response to antidepressant treatments. On other hand, effective non-pharmacological treatments for their tolerability addressed. Several affective used but strategies decreasing depression-related drugs side effects been focused recently. However, potential extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs), microRNAs (miRNAs) as cell-based paradigms, besides including mitochondrial transfer, plasma, transcranial direct current stimulation (tDCS), magnetic (TMS), exercise therapy needs further study. This review explores paradigms treatment. In addition, plasma therapy, mitotherapy, in several vitro vivo conditions experimental disease models along tDCS TMS will be discussed novel promising approaches.

Language: Английский

Citations

0
Early-Life Stress Caused by Maternal Deprivation Impacts Dendritic Morphology of Adult Male Mouse Neocortical Interneurons DOI Open Access

Mohammed M. Nakhal,

Lidya K. Yassin,

Shaikha Al Houqani

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 1909 - 1909

Published: Feb. 23, 2025

A substantial body of research suggests that early-life stress (ELS) is associated with neuropathology in adulthood. Maternal deprivation (MD) a commonly utilised model mice for the study specific neurological diseases. The appropriate growth dendrites essential optimal functioning nervous system. However, impact ELS on interneuron dendritic morphology remains unclear. To ascertain whether induces alterations GABAergic inhibitory interneurons layers II/III medial entorhinal cortex (mEC), somatosensory (SSC), motor (MC), and CA1 region hippocampus (Hp), 9-day-old male GAD-67-EGFP transgenic were subjected to 24 h MD. At postnatal day 60 (P60), animals sacrificed, their brains morphological analyses. results indicated MD affected interneurons. mean length segments examined cortical areas, except MC, significantly decreased, whereas number primary was unaffected. Furthermore, density GAD67-EGFP-positive decreased mEC Hp, but not MC. induction through developmental time window when significant changes occur rendered developing cells particularly susceptible stress, resulting reduction surviving at adult stage.

Language: Английский

Citations

0
Neurobiological intersections of stress and substance use disorders DOI Creative Commons
Vitor A. L. Juliano, Kairo Alan Albernaz-Mariano,

Luiza Helena Halas Covre

et al.

Frontiers in Neuroscience, Journal Year: 2025, Volume and Issue: 19

Published: May 1, 2025

Substance use has been intertwined with human history for millennia. Throughout the ages, people have consumed various substances medicinal, spiritual, and recreational reasons, although occasional differs significantly from substance disorders (SUDs). Exposure to lifetime stressors constitutes a significant risk factor both psychiatric SUD development relapse. Indeed, hypothalamic-pituitary-adrenal (HPA) axis modulation, alterations in neuroanatomical neurotransmitter systems, as well neuroinflammation are common features of stress-related mood SUDs. In this mini-review, we will explore how stress exposure influences SUDs' neurobiological basis on different scales-from large neural circuitries specific molecular mechanisms-and discuss novel targets potential treatments.

Language: Английский

Citations

0