Neuropsychopharmacology最新文献_第5页

Longevity, enhanced memory, and altered density of dendritic spines in hippocampal CA3 and dentate gyrus after hemizygous deletion of Pde2a in mice. 小鼠半杂合性缺失 Pde2a 后，海马 CA3 和齿状回的树突棘密度改变，寿命延长，记忆力增强。

IF 6.6 1区医学

Neuropsychopharmacology Pub Date : 2024-11-27 DOI: 10.1038/s41386-024-02031-w

Karsten Baumgärtel, Nicola J Broadbent, Hailing Su, Brittany Masatsugu, Karly P Maruyama, Robert W Johnson, Andrea L Green, Diana K Hornberger, Robert Petroski, Roderick Scott, Marco Peters

{"title":"Longevity, enhanced memory, and altered density of dendritic spines in hippocampal CA3 and dentate gyrus after hemizygous deletion of Pde2a in mice.","authors":"Karsten Baumgärtel, Nicola J Broadbent, Hailing Su, Brittany Masatsugu, Karly P Maruyama, Robert W Johnson, Andrea L Green, Diana K Hornberger, Robert Petroski, Roderick Scott, Marco Peters","doi":"10.1038/s41386-024-02031-w","DOIUrl":"https://doi.org/10.1038/s41386-024-02031-w","url":null,"abstract":"Studies using acute or subchronic pharmacological inhibition of phosphodiesterase 2 A (PDE2A) have led to its proposal as a target for treatment of cognitive deficits associated with neuropsychiatric and neurodegenerative disease. However, the impact of continuous inhibition of PDE2A on memory is unknown. Moreover, the neuroanatomical regions mediating memory enhancement have not been categorically identified. To address these open questions, we studied knockout mice and hippocampus restricted manipulations. Pde2a heterozygous knockout mice are viable with no gross histological abnormalities. The mice exhibit enhanced spatial and object recognition memory that is independent of anxiolytic effects and is paralleled by increased density of dendritic mushroom and thin spines in hippocampal CA3 and dentate gyrus in adult mice. In CA1, subtle alterations in spine density were seen, while theta-burst LTP and paired-pulse facilitation were normal. Spatial memory enhancement persists in aged Pde2a heterozygous knockout mice, and to our surprise these mice live significantly longer than wild-type littermate controls. In summary, we provide evidence that life-long reduction of PDE2A expression promotes spine formation and maturation, exerts beneficial effects on memory, and increases lifespan.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Endocannabinoid interference blocks post-global cerebral ischemia depression through prefrontal cortico-amygdala projections. 内源性大麻素干扰可通过前额叶皮质-杏仁核投射阻断大脑缺血后的抑郁。

IF 6.6 1区医学

Neuropsychopharmacology Pub Date : 2024-11-24 DOI: 10.1038/s41386-024-02029-4

Zhaoyuan Tu, Yao Ma, Huiping Shang, Sha Zhao, Bao Xue, Yu Qu, Jiangfan Chen, Yulong Li, Ji Hu, Fang Gao, Huamin Xu, Xufeng Xu, Xia Zhang

{"title":"Endocannabinoid interference blocks post-global cerebral ischemia depression through prefrontal cortico-amygdala projections.","authors":"Zhaoyuan Tu, Yao Ma, Huiping Shang, Sha Zhao, Bao Xue, Yu Qu, Jiangfan Chen, Yulong Li, Ji Hu, Fang Gao, Huamin Xu, Xufeng Xu, Xia Zhang","doi":"10.1038/s41386-024-02029-4","DOIUrl":"https://doi.org/10.1038/s41386-024-02029-4","url":null,"abstract":"Up to 45% of patients surviving from transient global cerebral ischemia (GCI) after cardiac arrest develop post-global cerebral ischemia depression (PGCID), but how to treat PGCID is clinically unknown. Here we find that cannabinoid type-1 receptor (CB1R) antagonists, CB1R knockout and endocannabinoid (eCB) synthesis inhibition block acute stress-induced PGCID. Application of acute stress to GCI mice increases CB1R activity from ventromedial prefrontal cortical (vmPFC) terminals synapsing with the basolateral amygdala (BLA) neurons, indicating the involvement of increased vmPFC-BLA synaptic eCB signaling in PGCID induction. This idea is supported by findings that optogenetic activation of CB1Rs in vmPFC-BLA projections mimics stress effects to induce PGCID, which is blocked by knock-down of eCB biosynthesis enzyme genes in vmPFC-BLA synapses. Interestingly, GCI mice show decreased mRNA expression of eCB degradation enzymes in vmPFCs without significant changes on mRNA expression of eCB biosynthesis and degradation enzymes in BLA cells. Thus, over-expression of eCB degradation enzymes in vmPFC cells innervating BLA neurons or activation of vmPFC-BLA projections blocks stress effects to induce PGCID. Our findings suggest that decreased eCB degradation and subsequent stress-increased eCB signaling in vmPFC-BLA circuits participate in the mechanism of PGCID, which can be treated clinically by eCB signaling interference systemically or in vmPFC-BLA circuits.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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In memoriam – George R. Breese, Ph.D 悼念乔治-R-布雷斯博士

IF 6.6 1区医学

Neuropsychopharmacology Pub Date : 2024-11-19 DOI: 10.1038/s41386-024-02026-7

Fulton T. Crews, Thomas L. Kash

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Decoding threat neurocircuitry representations during traumatic memory recall in PTSD 创伤后应激障碍患者在回忆创伤记忆时的威胁神经回路表征解码。

IF 6.6 1区医学

Neuropsychopharmacology Pub Date : 2024-11-19 DOI: 10.1038/s41386-024-02028-5

Kierra R. Morris, Michael Jaeb, Joseph E. Dunsmoor, Zachary N. Stowe, Josh M. Cisler

{"title":"Decoding threat neurocircuitry representations during traumatic memory recall in PTSD","authors":"Kierra R. Morris, Michael Jaeb, Joseph E. Dunsmoor, Zachary N. Stowe, Josh M. Cisler","doi":"10.1038/s41386-024-02028-5","DOIUrl":"10.1038/s41386-024-02028-5","url":null,"abstract":"The neurocircuitry mechanisms underlying recall of traumatic memories remain unclear. This study investigated whether traumatic memory recall engages neurocircuitry representations that mirror activity patterns engaged during generalized threat stimulus processing in Post Traumatic Stress Disorder (PTSD). Multivariate pattern analysis was used to train 3 decoders. A “trauma” decoder was trained on fMRI patterns during idiographic trauma versus neutral narratives in a sample of 73 adult women with PTSD. A separate cohort of 125 adult participants completed a reward and threat learning task, from which “shock” and “reward loss” decoders were trained on neural patterns during threat or reward outcome delivery, respectively. These decoders were then cross-tested on the alternative datasets, allowing analyses of the degree to which traumatic memory recall engaged neurocircuitry representations that overlap with more general aversive stimuli. Decoders were trained and tested in four networks related to salience processing as well bilateral amygdala and hippocampal masks. The shock decoder trained in a midcingulate / posterior insula network demonstrated elevated predictions for shock during traumatic versus neutral memory recall. Similarly, the trauma decoder made elevated predictions about trauma recall during shock versus no shock delivery across multiple networks related to salience processing. There was no overlap between reward loss decoder predictions and trauma memory recall or vice versa. PTSD participants with elevated re-experiencing symptoms demonstrated the highest engagement of shock activity patterns during trauma memory recall. These results suggest that trauma memory recall engages neurocircuitry representations that overlap with threat, specifically painful, stimulus delivery.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"50 3","pages":"568-575"},"PeriodicalIF":6.6,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Anterior piriform cortex dysfunction underlies autism spectrum disorders-related olfactory deficits in Fmr1 conditional deletion mice. Fmr1条件性缺失小鼠与自闭症谱系障碍相关的嗅觉缺陷是前梨状皮层功能障碍的基础。

IF 6.6 1区医学

Neuropsychopharmacology Pub Date : 2024-11-16 DOI: 10.1038/s41386-024-02027-6

Lingzhi Zhang, Chi Geng, Shan Li, Qingnan Tang, Penglai Liu, Wei Liu, Gaoxue Qiu, Anan Li, Ankang Hu, Fengjiao Chen

{"title":"Anterior piriform cortex dysfunction underlies autism spectrum disorders-related olfactory deficits in Fmr1 conditional deletion mice.","authors":"Lingzhi Zhang, Chi Geng, Shan Li, Qingnan Tang, Penglai Liu, Wei Liu, Gaoxue Qiu, Anan Li, Ankang Hu, Fengjiao Chen","doi":"10.1038/s41386-024-02027-6","DOIUrl":"https://doi.org/10.1038/s41386-024-02027-6","url":null,"abstract":"Previous studies indicated that ASD-related olfactory dysfunctions are rooted in the piriform cortex. However, the direct evidence supporting a causal link between the dysfunction of the piriform cortex and olfactory disorders in ASD is limited. In the present study, we explored the role of anterior piriform cortex (aPC) in ASD-related olfactory disorders by specifically ablating Fmr1, a leading known monogenic cause for ASD, in the pyramidal neurons. Our data demonstrated that the targeted deletion of Fmr1 in aPC pyramidal neurons was sufficient to induce deficits in olfactory detection. In vivo and in vitro electrophysiological recordings showed that the deletion of Fmr1 increased the activity of pyramidal neurons, exhibiting an enhanced excitatory response and a reduced inhibitory response upon odor stimulation. Furthermore, specific deletion of Fmr1 enhanced the power of beta oscillations during odor stimuli, meanwhile, disturbed excitatory and inhibitory synaptic transmission. The abnormal morphology of pyramidal neurons induced by the deletion of Fmr1 may be responsible for the impaired aPC neuronal function. These findings suggest that dysfunction of the aPC may play a role in olfactory impairments observed in ASD models related to Fmr1 deficiency.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Chronic Δ9-tetrahydrocannabinol exposure in adolescent nonhuman primates: persistent abnormalities in economic demand and brain functional connectivity 非人灵长类青少年长期接触Δ9-四氢大麻酚：经济需求和大脑功能连接的持续异常。

IF 6.6 1区医学

Neuropsychopharmacology Pub Date : 2024-11-13 DOI: 10.1038/s41386-024-02024-9

Brian D. Kangas, Harshawardhan U. Deshpande, Sarah L. Withey, Roger D. Spealman, Jack Bergman, Stephen J. Kohut

{"title":"Chronic Δ9-tetrahydrocannabinol exposure in adolescent nonhuman primates: persistent abnormalities in economic demand and brain functional connectivity","authors":"Brian D. Kangas, Harshawardhan U. Deshpande, Sarah L. Withey, Roger D. Spealman, Jack Bergman, Stephen J. Kohut","doi":"10.1038/s41386-024-02024-9","DOIUrl":"10.1038/s41386-024-02024-9","url":null,"abstract":"Although chronic cannabis use during adolescence can alter brain function and impair complex behavioral processes, it is unclear whether such deficits persist into adulthood. Using a coordinated awake neuroimaging and behavioral approach in nonhuman primates, we addressed this issue by examining the impact of chronic adolescent exposure to Δ9-tetrahydrocannabinol (THC) on brain functional connectivity and motivational processes during early adulthood. Female and male squirrel monkeys (n = 23) were treated daily for 6 months during adolescence with vehicle or either a low (0.32 mg/kg) or high dose (3.2 mg/kg) of THC. Regional homogeneity and seed-to-whole-brain functional connectivity were analyzed prior to, during, and following discontinuation of chronic treatment to examine changes in regions implicated in reward processing. Subsequently, motivation and reward sensitivity in these subjects, now young adults, were evaluated in economic demand studies by determining the relationship between escalating response requirements and consumption of differing magnitudes of a palatable food reinforcer. Results show that adolescent THC exposure led to persistent alterations in mOFC, caudate, and ventral striatum whole-brain connectivity. Moreover, subjects treated with vehicle during adolescence displayed an orderly and expected inverse relationship between reward magnitude and demand elasticity, whereas THC-treated subjects exhibited dosage-dependent disorder in reward sensitivity and motivational deficits. Changes in neural circuitry (local connectivity in ventral striatum and whole brain connectivity in mOFC) and economic demand were correlated with indices of reward sensitivity in vehicle- but not THC-treated subjects. Taken together, these data indicate that chronic adolescent THC exposure produced long-lasting neurocognitive abnormalities in reward processing.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"50 3","pages":"576-585"},"PeriodicalIF":6.6,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A sleepy cannabis constituent: cannabinol and its active metabolite influence sleep architecture in rats 令人昏昏欲睡的大麻成分：大麻酚及其活性代谢物影响大鼠的睡眠结构。

IF 6.6 1区医学

Neuropsychopharmacology Pub Date : 2024-11-12 DOI: 10.1038/s41386-024-02018-7

Jonathon C. Arnold, Cassandra V. Occelli Hanbury-Brown, Lyndsey L. Anderson, Miguel A. Bedoya-Pérez, Michael Udoh, Laura A. Sharman, Joel S. Raymond, Peter T. Doohan, Adam Ametovski, Iain S. McGregor

{"title":"A sleepy cannabis constituent: cannabinol and its active metabolite influence sleep architecture in rats","authors":"Jonathon C. Arnold, Cassandra V. Occelli Hanbury-Brown, Lyndsey L. Anderson, Miguel A. Bedoya-Pérez, Michael Udoh, Laura A. Sharman, Joel S. Raymond, Peter T. Doohan, Adam Ametovski, Iain S. McGregor","doi":"10.1038/s41386-024-02018-7","DOIUrl":"10.1038/s41386-024-02018-7","url":null,"abstract":"Medicinal cannabis is being used worldwide and there is increasing use of novel cannabis products in the community. Cannabis contains the major cannabinoids, Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), but also an array of minor cannabinoids that have undergone much less pharmacological characterization. Cannabinol (CBN) is a minor cannabinoid used in the community in “isolate’ products and is claimed to have pro-sleep effects comparable to conventional sleep medications. However, no study has yet examined whether it impacts sleep architecture using objective sleep measures. The effects of CBN on sleep in rats using polysomnography were therefore examined. CBN increased total sleep time, although there was evidence of biphasic effects with initial sleep suppression before a dramatic increase in sleep. CBN increased both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. The magnitude of the effect of CBN on NREM was comparable to the sleep aid zolpidem, although, unlike CBN, zolpidem did not influence REM sleep. Following CBN dosing, 11-hydroxy-CBN, a primary metabolite of CBN surprisingly attained equivalently high brain concentrations to CBN. 11-hydroxy-CBN was active at cannabinoid CB1 receptors with comparable potency and efficacy to Δ9-THC, however, CBN had much lower activity. We then discovered that the metabolite 11-hydroxy-CBN also influenced sleep architecture, albeit with some subtle differences from CBN itself. This study shows CBN affects sleep using objective sleep measures and suggests an active metabolite may contribute to its hypnotic action.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"50 3","pages":"586-595"},"PeriodicalIF":6.6,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11736144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mitogen-activated protein kinase dependent presynaptic potentiation in the lateral habenula mediates depressive-like behaviors in rats 依赖于突触前电位的外侧哈文神经元介导大鼠的抑郁样行为

IF 6.6 1区医学

Neuropsychopharmacology Pub Date : 2024-11-11 DOI: 10.1038/s41386-024-02025-8

Hoyong Park, Hakyun Ryu, Seungjae Zhang, Sungmin Kim, ChiHye Chung

{"title":"Mitogen-activated protein kinase dependent presynaptic potentiation in the lateral habenula mediates depressive-like behaviors in rats","authors":"Hoyong Park, Hakyun Ryu, Seungjae Zhang, Sungmin Kim, ChiHye Chung","doi":"10.1038/s41386-024-02025-8","DOIUrl":"10.1038/s41386-024-02025-8","url":null,"abstract":"Emerging evidence suggests that the enhanced activity of lateral habenula (LHb) is involved in depressive disorders. This abnormal potentiation of LHb neurons was shown to originate from presynaptic alterations; however, the mechanisms underlying this presynaptic enhancement and physiological consequences are yet to be elucidated. Previously, we reported that presynaptic transmission in the LHb is temporally rhythmic, showing greater activity in the afternoon than in the morning. Here, we used a learned helpless rodent model of depression to show that exposure to a stressor or incubation with the stress hormone, corticosterone, abolished the presynaptic temporal variation in the LHb. In addition, selective inhibition of mitogen-activated protein kinase (MAPK) kinase (MAPKK, MEK) activity in the LHb restored the presynaptic alteration even after stress exposure. Moreover, we observed a slight increase in phosphorylated synapsin I after stress exposure. Finally, we found that a blockade of MAPK signaling before stress exposure successfully prevented the depression-like behaviors, including behavioral despair and helplessness, in an acute learned helpless animal model of depression. Our study delineates the cellular and molecular mechanisms responsible for the abnormal presynaptic enhancement of the LHb in depression, which may mediate depressive behaviors.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"50 3","pages":"540-547"},"PeriodicalIF":6.6,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11735983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction: Punishment-resistant alcohol intake is mediated by the nucleus accumbens shell in female rats 更正：雌性大鼠耐受惩罚的酒精摄入量是由核团外壳介导的。

IF 6.6 1区医学

Neuropsychopharmacology Pub Date : 2024-11-07 DOI: 10.1038/s41386-024-02023-w

Allison J. McDonald, Panthea Nemat, Thijs van ‘t Hullenaar, Dustin Schetters, Yvar van Mourik, Isis Alonso-Lozares, Taco J. De Vries, Nathan J. Marchant

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Common and contrasting effects of 5-HTergic signaling in pyramidal cells and SOM interneurons of the mouse cortex. 5-HTergic 信号在小鼠大脑皮层锥体细胞和 SOM 中间神经元中的共同效应和对比效应。

IF 6.6 1区医学

Neuropsychopharmacology Pub Date : 2024-11-07 DOI: 10.1038/s41386-024-02022-x

Nathalie Schmitz, Sadat Hodzic, Therese Riedemann

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