eNeuro最新文献

{"title":"Adolescent Thalamoprefrontal Inhibition Leads to Changes in Intrinsic Prefrontal Network Connectivity.","authors":"David Petersen, Ricardo Raudales, Ariadna Kim Silva, Christoph Kellendonk, Sarah Canetta","doi":"10.1523/ENEURO.0284-24.2024","DOIUrl":"10.1523/ENEURO.0284-24.2024","url":null,"abstract":"<p><p>Adolescent inhibition of thalamocortical projections from postnatal days P20 to 50 leads to long-lasting deficits in prefrontal cortex function and cognition in the adult mouse. While this suggests a role of thalamic activity in prefrontal cortex maturation, it is unclear how inhibition of these projections affects prefrontal circuitry during adolescence. Here, we used chemogenetic tools to inhibit thalamoprefrontal projections in male/female mice from P20 to P35 and measured synaptic inputs to prefrontal pyramidal neurons by layer (either II/III or V/VI) and projection target (mediodorsal thalamus (MD), nucleus accumbens (NAc), or callosal prefrontal projections) 24 h later using slice physiology. We found a decrease in the frequency of excitatory and inhibitory currents in layer II/III NAc and layer V/VI MD-projecting neurons while layer V/VI NAc-projecting neurons showed an increase in the amplitude of excitatory and inhibitory currents. Regarding cortical projections, the frequency of inhibitory but not excitatory currents was enhanced in contralateral mPFC-projecting neurons. Notably, despite these complex changes in individual levels of excitation and inhibition, the overall balance between excitation and inhibition in each cell was only altered in the contralateral mPFC projections. This finding suggests homeostatic regulation occurs within subcortically but not intracortical callosal-projecting neurons. Increased inhibition of intraprefrontal connectivity may therefore be particularly important for prefrontal cortex circuit maturation. Finally, we observed cognitive deficits in the adult mouse using this narrowed window of thalamocortical inhibition.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11363513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotype Distinctions in Mice Deficient in the Neuron-Specific α3 Subunit of Na,K-ATPase: <i>Atp1a</i>3^tm1Ling/+ and <i>Atp1a3</i> ^+/D801Y.","authors":"Yi Bessie Liu, Elena Arystarkhova, Amanda N Sacino, Margit V Szabari, Cathleen M Lutz, Markus Terrey, Natalia S Morsci, Tatjana C Jakobs, Karin Lykke-Hartmann, Allison Brashear, Elenora Napoli, Kathleen J Sweadner","doi":"10.1523/ENEURO.0101-24.2024","DOIUrl":"10.1523/ENEURO.0101-24.2024","url":null,"abstract":"<p><p><i>ATP1A3</i> is a Na,K-ATPase gene expressed specifically in neurons in the brain. Human mutations are dominant and produce an unusually wide spectrum of neurological phenotypes, most notably rapid-onset dystonia parkinsonism (RDP) and alternating hemiplegia of childhood (AHC). Here we compared heterozygotes of two mouse lines, a line with little or no expression (<i>Atp1a</i>3^tm1Ling/+) and a knock-in expressing p.Asp801Tyr (D801Y, <i>Atp1a3</i> ^+/D801Y). Both mouse lines had normal lifespans, but <i>Atp1a3</i> ^+/D801Y had mild perinatal mortality contrasting with D801N mice (<i>Atp1a3</i> ^+/D801N), which had high mortality. The phenotypes of <i>Atp1a</i>3^tm1Ling/+ and <i>Atp1a3</i> ^+/D801Y were different, and testing of each strain was tailored to its symptom range. <i>Atp1a</i>3^tm1Ling/+ mice displayed little at baseline, but repeated ethanol intoxication produced hyperkinetic motor abnormalities not seen in littermate controls. <i>Atp1a3</i> ^+/D801Y mice displayed robust phenotypes: hyperactivity, diminished posture consistent with hypotonia, and deficiencies in beam walk and wire hang tests. Symptoms also included qualitative motor abnormalities that are not well quantified by conventional tests. Paradoxically, <i>Atp1a3</i> ^+/D801Y showed sustained better performance than wild type on the accelerating rotarod. <i>Atp1a3</i> ^+/D801Y mice were overactive in forced swimming and afterward had intense shivering, transient dystonic postures, and delayed recovery. Remarkably, <i>Atp1a3</i> ^+/D801Y mice were refractory to ketamine anesthesia, which elicited hyperactivity and dyskinesia even at higher dose. Neither mouse line exhibited fixed dystonia (typical of RDP patients), spontaneous paroxysmal weakness (typical of AHC patients), or seizures but had consistent, measurable neurological abnormalities. A gradient of variation supports the importance of studying multiple <i>Atp1a3</i> mutations in animal models to understand the roles of this gene in human disease.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11360364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Method for Evaluating Hunger and Thirst in Monkeys by Measuring Blood Ghrelin and Osmolality Levels.","authors":"Yuki Suwa, Jun Kunimatsu, Akua Kamata, Masayuki Matsumoto, Hiroshi Yamada","doi":"10.1523/ENEURO.0481-23.2024","DOIUrl":"10.1523/ENEURO.0481-23.2024","url":null,"abstract":"<p><p>Hunger and thirst drive animals' consumption behavior and regulate their decision-making concerning rewards. We previously assessed the thirst states of monkeys by measuring blood osmolality under controlled water access and examined how these thirst states influenced their risk-taking behavior in decisions involving fluid rewards. However, hunger assessment in monkeys remains poorly performed. Moreover, the lack of precise measures for hunger states leads to another issue regarding how hunger and thirst states interact with each other in each individual. Thus, when controlling food access to motivate performance, it remains unclear how these two physiological needs are satisfied in captive monkeys. Here, we measured blood ghrelin and osmolality levels to respectively assess hunger and thirst in four captive macaques. Using an enzyme-linked immunosorbent assay, we identified that the levels of blood ghrelin, a widely measured hunger-related peptide hormone in humans, were high after 20 h of no food access (with <i>ad libitum</i> water). This reflects a typical controlled food access condition. One hour after consuming a regular dry meal, the blood ghrelin levels in three out of four monkeys decreased to within their baseline range. Additionally, blood osmolality measured from the same blood sample, the standard hematological index of hydration status, increased after consuming the regular dry meal with no water access. Thus, ghrelin and osmolality may reflect the physiological states of individual monkeys regarding hunger and thirst, suggesting that these indices can be used as tools for monitoring hunger and thirst levels that mediate an animal's decision to consume rewards.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11361293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141626324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transsynaptic BMP Signaling Regulates Fine-Scale Topography between Adjacent Sensory Neurons.","authors":"Takuya Kaneko, Ruonan Li, Qun He, Limin Yang, Bing Ye","doi":"10.1523/ENEURO.0322-24.2024","DOIUrl":"10.1523/ENEURO.0322-24.2024","url":null,"abstract":"<p><p>Sensory axons projecting to the central nervous system are organized into topographic maps that represent the locations of sensory stimuli. In some sensory systems, even adjacent sensory axons are arranged topographically, forming \"fine-scale\" topographic maps. Although several broad molecular gradients are known to instruct coarse topography, we know little about the molecular signaling that regulates fine-scale topography at the level of two adjacent axons. Here, we provide evidence that transsynaptic bone morphogenetic protein (BMP) signaling mediates local interneuronal communication to regulate fine-scale topography in the nociceptive system of <i>Drosophila</i> larvae. We first show that the topographic separation of the axon terminals of adjacent nociceptors requires their common postsynaptic target, the A08n neurons. This phenotype is recapitulated by knockdown of the BMP ligand, Decapentaplegic (Dpp), in these neurons. In addition, removing the Type 2 BMP receptors or their effector (Mad transcription factor) in single nociceptors impairs the fine-scale topography, suggesting the contribution of BMP signaling originated from A08n. This signaling is likely mediated by phospho-Mad in the presynaptic terminals of nociceptors to ensure local interneuronal communication. Finally, reducing Dpp levels in A08n reduces the nociceptor-A08n synaptic contacts. Our data support that transsynaptic BMP signaling establishes the fine-scale topography by facilitating the formation of topographically correct synapses. Local BMP signaling for synapse formation may be a developmental strategy that independently regulates neighboring axon terminals for fine-scale topography.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11360983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The White Matter Integrity and Functional Connection Differences of Fornix (Cres)/Stria Terminalis in Individuals with Mild Cognitive Impairment Induced by Occupational Aluminum Exposure.","authors":"Feifei Zhang, Yangyang Li, Ruihong Chen, Pengxin Shen, Xiaochun Wang, Huaxing Meng, Jiangfeng Du, Guoqiang Yang, Bo Liu, Qiao Niu, Hui Zhang, Yan Tan","doi":"10.1523/ENEURO.0128-24.2024","DOIUrl":"10.1523/ENEURO.0128-24.2024","url":null,"abstract":"<p><p>Long-term aluminum (Al) exposure increases the risk of mild cognitive impairment (MCI). The aim of the present study was to investigate the neural mechanisms of Al-induced MCI. In our study, a total of 52 individuals with occupational Al exposure >10 years were enrolled and divided into two groups: MCI (Al-MCI) and healthy controls (Al-HC). Plasma Al concentrations and Montreal Cognitive Assessment (MoCA) score were collected for all participants. And diffusion tensor imaging and resting-state functional magnetic resonance imaging were used to examine changes of white matter (WM) and functional connectivity (FC). There was a negative correlation between MoCA score and plasma Al concentration. Compared with the Al-HC, fractional anisotropy value for the right fornix (cres)/stria terminalis (FX/ST) was higher in the Al-MCI. Furthermore, there was a difference in FC between participants with and without MCI under Al exposure. We defined the regions with differing FC as a \"pathway,\" specifically the connectivity from the right temporal pole to the right FX/ST, then to the right sagittal stratum, and further to the right anterior cingulate and paracingulate gyri and right inferior frontal gyrus, orbital part. In summary, we believe that the observed differences in WM integrity and FC in the right FX/ST between participants with and without MCI under long-term Al exposure may represent the neural mechanisms underlying MCI induced by Al exposure.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11360986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141981980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing Cross-Contamination in Spike-Sorted Electrophysiology Data.","authors":"Jack P Vincent, Michael N Economo","doi":"10.1523/ENEURO.0554-23.2024","DOIUrl":"10.1523/ENEURO.0554-23.2024","url":null,"abstract":"<p><p>Recent advances in extracellular electrophysiology now facilitate the recording of spikes from hundreds or thousands of neurons simultaneously. This has necessitated both the development of new computational methods for spike sorting and better methods to determine spike-sorting accuracy. One long-standing method of assessing the false discovery rate (FDR) of spike sorting-the rate at which spikes are assigned to the wrong cluster-has been the rate of interspike interval (ISI) violations. Despite their near ubiquitous usage in spike sorting, our understanding of how exactly ISI violations relate to FDR, as well as best practices for using ISI violations as a quality metric, remains limited. Here, we describe an analytical solution that can be used to predict FDR from the ISI violation rate (ISI_v). We test this model in silico through Monte Carlo simulation and apply it to publicly available spike-sorted electrophysiology datasets. We find that the relationship between ISI_v and FDR is highly nonlinear, with additional dependencies on firing frequency, the correlation in activity between neurons, and contaminant neuron count. Predicted median FDRs in public datasets recorded in mice were found to range from 3.1 to 50.0%. We found that stochasticity in the occurrence of ISI violations as well as uncertainty in cluster-specific parameters make it difficult to predict FDR for single clusters with high confidence but that FDR can be estimated accurately across a population of clusters. Our findings will help the growing community of researchers using extracellular electrophysiology assess spike-sorting accuracy in a principled manner.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141878514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Local Synthesis of Estradiol in the Rostral Ventromedial Medulla Protects against Widespread Muscle Pain in Male Mice.","authors":"Ashley N Plumb, Joseph B Lesnak, Louis J Kolling, Catherine A Marcinkiewcz, Kathleen A Sluka","doi":"10.1523/ENEURO.0332-24.2024","DOIUrl":"10.1523/ENEURO.0332-24.2024","url":null,"abstract":"<p><p>Animal studies consistently demonstrate that testosterone is protective against pain in multiple models, including an animal model of activity-induced muscle pain. In this model, females develop widespread muscle hyperalgesia, and reducing testosterone levels in males results in widespread muscle hyperalgesia. Widespread pain is believed to be mediated by changes in the central nervous system, including the rostral ventromedial medulla (RVM). The enzyme that converts testosterone to estradiol, aromatase, is highly expressed in the RVM. Therefore, we hypothesized that testosterone is converted by aromatase to estradiol locally in the RVM to prevent development of widespread muscle hyperalgesia in male mice. This was tested through pharmacological inhibition of estrogen receptors (ERs), aromatase, or ER-α in the RVM which resulted in contralateral hyperalgesia in male mice (C57BL/6J). ER inhibition in the RVM had no effect on hyperalgesia in female mice. As prior studies show modulation of estradiol signaling alters GABA receptor and transporter expression, we examined if removal of testosterone in males would decrease mRNA expression of GABA receptor subunits and vesicular GABA transporter (VGAT). However, there were no differences in mRNA expression of GABA receptor subunits of VGAT between gonadectomized and sham control males. Lastly, we used RNAscope to determine expression of ER-α in the RVM and show expression in inhibitory (VGAT+), serotonergic (tryptophan hydroxylase 2+), and μ-opioid receptor expressing (MOR+) cells. In conclusion, testosterone protects males from development of widespread hyperalgesia through aromatization to estradiol and activation of ER-α which is widely expressed in multiple cell types in the RVM.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11360981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of Comorbid Chronic Neuropathic Pain and Anxiety-Like Behaviors by Glutamatergic Neurons in the Ventrolateral Periaqueductal Gray and the Analgesic and Anxiolytic Effects of Electroacupuncture.","authors":"Xixiao Zhu, Chi Zhang, Yuxin Hu, Yifang Wang, Siqi Xiao, Yichen Zhu, Haiju Sun, Jing Sun, Chi Xu, Yunyun Xu, Yuerong Chen, Xiaofen He, Boyu Liu, Jinggen Liu, Junying Du, Yi Liang, Boyi Liu, Xiaoyu Li, Yongliang Jiang, Zui Shen, Xiaomei Shao, Jianqiao Fang","doi":"10.1523/ENEURO.0454-23.2024","DOIUrl":"10.1523/ENEURO.0454-23.2024","url":null,"abstract":"<p><p>Comorbid chronic neuropathic pain and anxiety is a common disease that represents a major clinical challenge. The underlying mechanisms of chronic neuropathic pain and anxiety are not entirely understood, which limits the exploration of effective treatment methods. Glutamatergic neurons in the ventrolateral periaqueductal gray (vlPAG) have been implicated in regulating pain, but the potential roles of the vlPAG in neuropathic pain-induced anxiety have not been investigated. Herein, whole-cell recording and immunofluorescence showed that the excitability of CamkIIα neurons in the vlPAG (vlPAG^CamkIIα+ neurons) was decreased in mice with spared nerve injury (SNI), while electroacupuncture (EA) activated these neurons. We also showed that chemogenetic inhibition of vlPAG^CamkIIα+ neurons resulted in allodynia and anxiety-like behaviors in naive mice. Furthermore, chemogenetic activation of vlPAG^CamkIIα+ neurons reduced anxiety-like behaviors and allodynia in mice with SNI, and EA had a similar effect in alleviating these symptoms. Nevertheless, EA combined with chemogenetic activation failed to further relieve allodynia and anxiety-like behaviors. Artificial inhibition of vlPAG^CamkIIα+ neurons abolished the analgesic and anxiolytic effects of EA. Overall, our study reveals a novel mechanism of neuropathic pain-induced anxiety and shows that EA may relieve comorbid chronic neuropathic pain and anxiety by activating vlPAG^CamkIIα+ neurons.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11360982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Measures of Implicit and Explicit Adaptation Do Not Linearly Add.","authors":"Bernard Marius 't Hart, Urooj Taqvi, Raphael Q Gastrock, Jennifer E Ruttle, Shanaathanan Modchalingam, Denise Y P Henriques","doi":"10.1523/ENEURO.0021-23.2024","DOIUrl":"10.1523/ENEURO.0021-23.2024","url":null,"abstract":"<p><p>Moving effectively is essential for any animal. Thus, many different kinds of brain processes likely contribute to learning and adapting movement. How these contributions are combined is unknown. Nevertheless, the field of motor adaptation has been working under the assumption that measures of explicit and implicit motor adaptation can simply be added in total adaptation. While this has been tested, we show that these tests were insufficient. We put this additivity assumption to the test in various ways and find that measures of implicit and explicit adaptation are not additive. This means that future studies should measure both implicit and explicit adaptation directly. It also challenges us to disentangle how various motor adaptation processes do combine when producing movements and may have implications for our understanding of other kinds of learning as well (data and code: https://osf.io/3yhw5).</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":"11 8","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11351015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic Stress Alters Synaptic Inhibition/Excitation Balance of Pyramidal Neurons But Not PV Interneurons in the Infralimbic and Prelimbic Cortices of C57BL/6J Mice.","authors":"Diana Rodrigues, Cátia Santa, Bruno Manadas, Patrícia Monteiro","doi":"10.1523/ENEURO.0053-24.2024","DOIUrl":"10.1523/ENEURO.0053-24.2024","url":null,"abstract":"<p><p>The medial prefrontal cortex (mPFC) plays a pivotal role in regulating working memory, executive function, and self-regulatory behaviors. Dysfunction in the mPFC circuits is a characteristic feature of several neuropsychiatric disorders including schizophrenia, depression, and post-traumatic stress disorder. Chronic stress (CS) is widely recognized as a major triggering factor for the onset of these disorders. Although evidence suggests synaptic dysfunction in mPFC circuits following CS exposure, it remains unclear how different neuronal populations in the infralimbic (IL) and prelimbic (PL) cortices are affected in terms of synaptic inhibition/excitation balance (<i>I</i>/<i>E</i> ratio). Here, using neuroproteomic analysis and whole-cell patch-clamp recordings in pyramidal neurons (PNs) and parvalbumin (PV) interneurons within the PL and IL cortices, we examined the synaptic changes after 21 d of chronic unpredictable stress, in male mice. Our results reveal distinct impacts of CS on PL and IL PNs, resulting in an increased <i>I</i>/<i>E</i> ratio in both subregions but through different mechanisms: CS increases inhibitory synaptic drive in the PL while decreasing excitatory synaptic drive in the IL. Notably, the <i>I</i>/<i>E</i> ratio and excitatory and inhibitory synaptic drive of PV interneurons remained unaffected in both PL and IL circuits following CS exposure. These findings offer novel mechanistic insights into the influence of CS on mPFC circuits and support the hypothesis of stress-induced mPFC hypofunction.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11351013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}