Neurobiology of Stress最新文献

{"title":"Intra-BLA alteration of interneurons’ modulation of activity in rats, reveals a dissociation between effects on anxiety symptoms and extinction learning","authors":"Rinki Saha ,&nbsp;Lisa-Sophie Wüstner ,&nbsp;Darpan Chakraborty ,&nbsp;Rachel Anunu ,&nbsp;Silvia Mandel ,&nbsp;Joyeeta Dutta Hazra ,&nbsp;Martin Kriebel ,&nbsp;Hansjuergen Volkmer ,&nbsp;Hanoch Kaphzan ,&nbsp;Gal Richter-Levin","doi":"10.1016/j.ynstr.2024.100681","DOIUrl":"10.1016/j.ynstr.2024.100681","url":null,"abstract":"<div><div>The basolateral amygdala (BLA) is a dynamic brain region involved in emotional experiences and subject to long-term plasticity. The BLA also modulates activity, plasticity, and related behaviors associated with other brain regions, including the mPFC and hippocampus. Accordingly, intra-BLA plasticity can be expected to alter both BLA-dependent behaviors and behaviors mediated by other brain regions. Lasting intra-BLA plasticity may be considered a form of metaplasticity, since it will affect subsequent plasticity and response to challenges later on. Activity within the BLA is tightly modulated by GABAergic interneurons, and thus inducing lasting alteration of GABAergic modulation of principal neurons may have an impactful metaplastic effect on BLA functioning. Previously, we demonstrated that intra-BLA knockdown (KD) of neurofascin (NF) reduced GABAergic synapses exclusively at the axon initial segment (AIS). Here, by reducing the expression of the tyrosine kinase receptor ephrin A7 (EphA7), we selectively impaired the modulatory function of a different subpopulation of interneurons, specifically targeting the soma and proximal dendrites of principal neurons. This perturbation induced an expected reduction in the spontaneous inhibitory synaptic input and an increase in the excitatory spontaneous synaptic activity, most probably due to the reduction of inhibitory tone. Moreover, this increased synaptic activity was followed by a reduction in intrinsic excitability. While intra-BLA NF-KD resulted in impaired extinction learning, without increased symptoms of anxiety, intra-BLA reduction of EphA7 expression resulted in increased symptoms of anxiety, as measured in the elevated plus maze, but without affecting fear conditioning or extinction learning. These results confirm the role of the BLA and intra-BLA metaplasticity in stress-induced increased anxiety symptoms and in impaired fear extinction learning but reveals a difference in intra-BLA mechanisms involved. The results also confirm the contribution of GABAergic interneurons to these effects but indicate selective roles for different subpopulations of intra-BLA interneurons.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"33 ","pages":"Article 100681"},"PeriodicalIF":4.3,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142526524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic analysis of rat prefrontal cortex following chronic stress induced by social isolation – Relevance to psychiatric and neurodevelopmental illness, and implications for treatment","authors":"Jen-Yin Goh ,&nbsp;Patricia Rueda ,&nbsp;Joy Taylor ,&nbsp;Alex Rathbone ,&nbsp;Daniel Scott ,&nbsp;Christopher J. Langmead ,&nbsp;Kevin C.F. Fone ,&nbsp;Gregory D. Stewart ,&nbsp;Madeleine V. King","doi":"10.1016/j.ynstr.2024.100679","DOIUrl":"10.1016/j.ynstr.2024.100679","url":null,"abstract":"<div><div>Social isolation is an established risk factor for psychiatric illness, and became increasingly topical with the spread of SARS-CoV-2. We used RNA sequencing (RNA-Seq) to enable unbiased assessment of transcriptomic changes within the prefrontal cortex (PFC) of isolation-reared rats. To provide insight into the relevance of this manipulation for studying human illness, we compared differentially expressed genes (DEGs) and enriched biological functions against datasets involving post-mortem frontal cortical tissue from patients with psychiatric and neurodevelopmental illnesses. Sixteen male Sprague-Dawley rats were reared in groups of four or individually from weaning on postnatal day (PND) 22–24 until PFC tissue collection for RNA-Seq (PND64-66). We identified a total of 183 DEGs in isolates, of which 128 mirrored those in PFC tissue from patients with stress-related mental illnesses and/or neurodevelopmental conditions featuring social deficits. Seventy-one encode proteins classed as druggable by the gene-drug interaction database. Interestingly there are antagonists or inhibitors for the products of three of these up-regulated DEGs (<em>Hrh3</em>, <em>Snca</em> and <em>Sod1</em>) and agonists or activators for products of six of these down-regulated DEGs (<em>Chrm4</em>, <em>Klf2</em>, <em>Lrrk2</em>, <em>Nr4a1</em>, <em>Nr4a3</em> and <em>Prkca</em>). Some have already undergone pre-clinical and clinical evaluation, and studies with the remainder may be warranted. Changes to <em>Hrh3</em>, <em>Sod1</em>, <em>Chrm4</em>, <em>Lrrk2</em>, <em>Nr4a1</em> and <em>Prkca</em> were replicated in an independent cohort of sixteen male Sprague-Dawley rats via quantitative reverse transcription polymerase chain reaction (qRT-PCR). Our findings support the continued use of post-weaning isolation rearing to investigate the neurobiology of stress-related disorders and evaluate therapeutic targets.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"33 ","pages":"Article 100679"},"PeriodicalIF":4.3,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142526671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cholecystokinin-expressing interneurons mediated inhibitory transmission and plasticity in basolateral amygdala modulate stress-induced anxiety-like behaviors in mice","authors":"Wei Fang ,&nbsp;Xi Chen ,&nbsp;Jufang He","doi":"10.1016/j.ynstr.2024.100680","DOIUrl":"10.1016/j.ynstr.2024.100680","url":null,"abstract":"<div><div>The basolateral amygdala (BLA) hyperactivity has been implicated in the pathophysiology of anxiety disorders. We recently found that enhancing inhibitory transmission in BLA by chemo-genetic activation of local interneurons (INs) can reduce stress-induced anxiety-like behaviors in mice. Cholecystokinin interneurons (CCK-INs) are a major part of INs in BLA. It remains unknown whether CCK-INs modulated inhibition in BLA can mediate anxiety. In the present study, we found that BLA CCK-INs project extensively to most local excitatory neurons. Activating these CCK-INs using chemo-genetics and optogenetics can both effectively suppress electrical-induced neuronal activity within the BLA. Additionally, we observed that direct and sustained activation of CCK-INs within the BLA via chemo-genetics can mitigate stress-induced anxiety-like behaviors in mice and reduce stress-induced hyperactivity within the BLA itself. Furthermore, augmenting inhibitory plasticity within the BLA through a brief, 10-min high-frequency laser stimulation (HFLS) of CCK-INs also reduce stress-induced anxiety-like behaviors in mice. Collectively, these findings underscore the pivotal role of BLA CCK-IN-mediated inhibitory transmission and plasticity in modulating anxiety.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"33 ","pages":"Article 100680"},"PeriodicalIF":4.3,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142526670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emotional comorbidities in epilepsy result from seizure-induced corticosterone activity","authors":"Renaud C. Gom ,&nbsp;Antis G. George ,&nbsp;Sydney A. Harris ,&nbsp;Pasindu Wickramarachchi ,&nbsp;Dhyey Bhatt ,&nbsp;Shaona Acharjee ,&nbsp;Quentin J. Pittman ,&nbsp;Matthew N. Hill ,&nbsp;Roberto Colangeli ,&nbsp;G. Campbell Teskey","doi":"10.1016/j.ynstr.2024.100678","DOIUrl":"10.1016/j.ynstr.2024.100678","url":null,"abstract":"<div><div>People with epilepsy often have psychiatric comorbidities that can significantly impair their quality of life. We previously reported that repeated seizure activity persistently alters endocannabinoid (eCB) signaling in the amygdala which accounts for comorbid emotional dysregulation in rats, however, the mechanism by which these alterations in eCB signaling within the epileptic brain occur is unclear. Endocannabinoid signaling is influenced by corticosterone (CORT) to modulate cognitive and emotional processes and a hyperactive hypothalamic-pituitary-adrenal (HPA) axis occurs in both people with epilepsy and nonhuman animal models of epilepsy.</div><div>We employed selective pharmacological tools and a variety of approaches including whole-cell patch-clamp electrophysiology, behavioural paradigms and biochemical assays in amygdala kindled adult male Long-Evans rats. We aimed to determine whether seizures induce hypersecretion of CORT and the role this plays in eCB system dysregulation, impaired fear memory, and anxiety-like behaviours associated with seizure activity.</div><div>Plasma CORT levels were significantly and consistently elevated following seizures over the course of kindling. Pre-seizure administration with the CORT synthesis inhibitor metyrapone prevented this seizure-induced CORT increase, prevented amygdala anandamide downregulation, and synaptic alteration induced by seizure activity. Moreover, treatment with metyrapone or combined glucocorticoid receptor (GR)/mineralocorticoid receptor (MR) antagonists prior to each elicited seizure were equally effective in preventing chronically altered anxiety-like behaviour and fear memory responses.</div><div>Inhibiting seizure-induced corticosterone synthesis, or directly blocking the effects of CORT at GR/MR prevents deleterious changes in emotional processing and could be a treatment option for emotional comorbidities in epilepsy.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"33 ","pages":"Article 100678"},"PeriodicalIF":4.3,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142526669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic changes of media prefrontal cortex astrocytic activity in response to negative stimuli in male mice","authors":"Ai-Mei Wu ,&nbsp;Jing-Ya Zhang ,&nbsp;Wei-Zhong Lun ,&nbsp;Zhi Geng ,&nbsp;Ye Yang ,&nbsp;Jun-Cang Wu ,&nbsp;Gui-Hai Chen","doi":"10.1016/j.ynstr.2024.100676","DOIUrl":"10.1016/j.ynstr.2024.100676","url":null,"abstract":"<div><div>Astrocytes play significant roles in regulating the central stress response. Chronic stress impairs the structure and function of astrocytes in many brain regions such as media prefrontal cortex (mPFC) in multiple neuropsychiatric conditions, but the astrocytic dynamics on the timescale of behavior remains unclear. Here, we recorded mPFC astrocytic activity in freely behaving mice and found that astrocytes are activated immediately by different aversive stimuli. Astrocyte specific GCaMP6s calcium indicator were virally expressed in mPFC astrocytes and fiber photometry experiments revealed that astrocytes are activated by tail-restraint (TRT), foot shock (FS), open arm exploration, stressor of height, predator odor and social defeat (SD) stress. ΔF/F analyses demonstrated that an unpredictable stimulus such as elevated platform stress (EPS) at the initial encounter induced the most intense and rapid changes in astrocytic calcium activity, while a predictable 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) stimulus resulted in the weakest response with a longer peak latency. In TRT, FS or SD test, a somatic stimulus led to higher average calcium activity level and faster average peak latency in repeated trails. Similar to TMT stimulus, astrocytic calcium activity in elevated plus maze (EPM) test exhibited a smaller average change in amplitude and the longest peak latency during open arm exploration. Moreover, astrocytic calcium activity exhibited different changes across behavioral states in SD tests. Our findings show that mPFC astrocytes exhibit distinct patterns of calcium activity in response to various negative stimuli, indicating that the dynamic activity of astrocytes may reflect the stress-related behavioral state under different stimulus conditions.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"33 ","pages":"Article 100676"},"PeriodicalIF":4.3,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142420393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Behavioral and neural correlates of diverse conditioned fear responses in male and female rats","authors":"Julia R. Mitchell ,&nbsp;Lindsay Vincelette ,&nbsp;Samantha Tuberman ,&nbsp;Vivika Sheppard ,&nbsp;Emmett Bergeron ,&nbsp;Roberto Calitri ,&nbsp;Rose Clark ,&nbsp;Caitlyn Cody ,&nbsp;Akshara Kannan ,&nbsp;Jack Keith ,&nbsp;Abigail Parakoyi ,&nbsp;MaryClare Pikus ,&nbsp;Victoria Vance ,&nbsp;Leena Ziane ,&nbsp;Heather Brenhouse ,&nbsp;Mikaela A. Laine ,&nbsp;Rebecca M. Shansky","doi":"10.1016/j.ynstr.2024.100675","DOIUrl":"10.1016/j.ynstr.2024.100675","url":null,"abstract":"<div><div>Pavlovian fear conditioning is a widely used tool that models associative learning in rodents. For decades the field has used predominantly male rodents and focused on a sole conditioned fear response: freezing. However, recent work from our lab and others has identified darting as a female-biased conditioned response, characterized by an escape-like movement across a fear conditioning chamber. It is also accompanied by a behavioral phenotype: Darters reliably show decreased freezing compared to Non-darters and males and reach higher velocities in response to the foot shock (“shock response”). However, the relationship between shock response and conditioned darting is not known. This study investigated if this link is due to differences in general processing of aversive stimuli between Darters, Non-darters and males. Across a variety of modalities, including corticosterone measures, the acoustic startle test, and sensitivity to thermal pain, Darters were found not to be more reactive or sensitive to aversive stimuli, and, in some cases, they appear less reactive to Non-darters and males. Analyses of cFos activity in regions involved in pain and fear processing following fear conditioning identified discrete patterns of expression among Darters, Non-darters, and males exposed to low and high intensity foot shocks. The results from these studies further our understanding of the differences between Darters, Non-darters and males and highlight the importance of studying individual differences in fear conditioning as indicators of fear state.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"33 ","pages":"Article 100675"},"PeriodicalIF":4.3,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352289524000717/pdfft?md5=4b62059f360b89745fab62771589e0b0&pid=1-s2.0-S2352289524000717-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142312606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early life stress induced sex-specific changes in behavior is paralleled by altered locus coeruleus physiology in BALB/cJ mice","authors":"Savannah Brannan,&nbsp;Lauren Garbe,&nbsp;Ben D. Richardson","doi":"10.1016/j.ynstr.2024.100674","DOIUrl":"10.1016/j.ynstr.2024.100674","url":null,"abstract":"<div><div>Adverse childhood experiences have been associated with many neurodevelopmental and affective disorders including attention deficit hyperactivity disorder and generalized anxiety disorder, with more exposures increasing negative risk. Sex and genetic background are biological variables involved in adverse psychiatric outcomes due to early life trauma. Females in general have an increased prevalence of stress-related psychopathologies beginning after adolescence, indicative of adolescence being a female-specific sensitive period. To understand the underlying neuronal mechanisms potentially responsible for this relationship between genetic background, sex, stress/trauma, and cognitive/affective behaviors, we assessed behavioral and neuronal changes in a novel animal model of early life stress exposure. Male and female BALB/cJ mice that express elevated basal anxiety-like behaviors and differences in monoamine signaling-associated genes, were exposed to an early life variable stress protocol that combined deprivation in early life with unpredictability in adolescence. Stress exposure produced hyperlocomotion and attention deficits (5-choice serial reaction time task) in male and female mice along with female-specific increased anxiety-like behavior. These behavioral changes were paralleled by reduced excitability of locus coeruleus (LC) neurons, due to resting membrane potential hyperpolarization in males and a female-specific increase in action potential delay time. These data describe a novel interaction between sex, genetic background, and early life stress that results in behavioral changes in clinically relevant domains and potential underlying mechanistic lasting changes in physiological properties of neurons in the LC.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"33 ","pages":"Article 100674"},"PeriodicalIF":4.3,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352289524000705/pdfft?md5=619d3e35ab97587f0de791597ebd7efb&pid=1-s2.0-S2352289524000705-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142316279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of chronic stress on cognitive function – From neurobiology to intervention","authors":"Milena Girotti ,&nbsp;Sarah E. Bulin,&nbsp;Flavia R. Carreno","doi":"10.1016/j.ynstr.2024.100670","DOIUrl":"10.1016/j.ynstr.2024.100670","url":null,"abstract":"<div><p>Exposure to chronic stress contributes considerably to the development of cognitive impairments in psychiatric disorders such as depression, generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and addictive behavior. Unfortunately, unlike mood-related symptoms, cognitive impairments are not effectively treated by available therapies, a situation in part resulting from a still incomplete knowledge of the neurobiological substrates that underly cognitive domains and the difficulty in generating interventions that are both efficacious and safe.</p><p>In this review, we will present an overview of the cognitive domains affected by stress with a specific focus on cognitive flexibility, behavioral inhibition, and working memory. We will then consider the effects of stress on neuronal correlates of cognitive function and the factors which may modulate the interaction of stress and cognition. Finally, we will discuss intervention strategies for treatment of stress-related disorders and gaps in knowledge with emerging new treatments under development.</p><p>Understanding how cognitive impairment occurs during exposure to chronic stress is crucial to make progress towards the development of new and effective therapeutic approaches.</p></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"33 ","pages":"Article 100670"},"PeriodicalIF":4.3,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352289524000663/pdfft?md5=74817e2bd3e26a3097145e164803e3b3&pid=1-s2.0-S2352289524000663-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142157401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enduring memory consequences of early-life stress / adversity: Structural, synaptic, molecular and epigenetic mechanisms","authors":"Tallie Z. Baram ,&nbsp;Matthew T. Birnie","doi":"10.1016/j.ynstr.2024.100669","DOIUrl":"10.1016/j.ynstr.2024.100669","url":null,"abstract":"<div><p>Adverse early life experiences are strongly associated with reduced cognitive function throughout life. The link is strong in many human studies, but these do not enable assigning causality, and the limited access to the live human brain can impede establishing the mechanisms by which early-life adversity (ELA) may induce cognitive problems. In experimental models, artificially imposed chronic ELA/stress results in deficits in hippocampus dependent memory as well as increased vulnerability to the deleterious effects of adult stress on memory. This causal relation of ELA and life-long memory impairments provides a framework to probe the mechanisms by which ELA may lead to human cognitive problems. Here we focus on the consequences of a one-week exposure to adversity during early postnatal life in the rodent, the spectrum of the ensuing memory deficits, and the mechanisms responsible. We highlight molecular, cellular and circuit mechanisms using convergent trans-disciplinary approaches aiming to enable translation of the discoveries in experimental models to the clinic.</p></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"33 ","pages":"Article 100669"},"PeriodicalIF":4.3,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352289524000651/pdfft?md5=0dae508822ab66e17bb389e4c4ca6c65&pid=1-s2.0-S2352289524000651-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142164492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct populations of lateral preoptic nucleus neurons jointly contribute to depressive-like behaviors through divergent projections in male mice","authors":"Zhiping Cao ,&nbsp;Wing-Ho Yung ,&nbsp;Ya Ke","doi":"10.1016/j.ynstr.2024.100667","DOIUrl":"10.1016/j.ynstr.2024.100667","url":null,"abstract":"<div><p>The lateral preoptic area (LPO) is a component of the hypothalamus involved in various physiological functions including sleep-wakefulness transition, thermoregulation, and water-salt balance. In this study, we discovered that distinct LPO excitatory neurons project separately to the aversive processing center lateral habenula (LHb) and the reward processing hub ventral tegmental area (VTA). Following chronic restraint stress (CRS), the LHb-projecting and VTA-projecting LPO neurons exhibited increased and decreased neuronal activities, respectively. Optogenetic activation of LHb-projecting LPO excitatory neurons and LPO excitatory neuronal terminals within LHb evoked aversion and avoidance behaviors, while activation of VTA-projecting LPO excitatory neurons and LPO excitatory neuronal terminals within VTA produced preference and exploratory behaviors in mice. Furthermore, either optogenetic inhibition of LHb-projecting LPO excitatory neurons or activation of VTA-projecting LPO excitatory neurons during CRS effectively prevented the development of depressive-like behaviors. Our study unveils, for the first-time, divergent pathways originating from LPO that regulate opposite affective states in mice and implicates that an imbalance of their activities could lead to depressive-like behaviors. These circuitries represent promising therapeutic targets to relieve emotional dysfunctions in neuropsychiatric disorders.</p></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"32 ","pages":"Article 100667"},"PeriodicalIF":4.3,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352289524000638/pdfft?md5=1523f24ce25ac9686ea2b799467f5764&pid=1-s2.0-S2352289524000638-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141979596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}