eNeuro最新文献

{"title":"Neuronal network inactivity potentiates neuropeptide release from mouse cortical neurons.","authors":"Theresa Priebe, Aygul Subkhangulova, Ruud F Toonen, Matthijs Verhage","doi":"10.1523/ENEURO.0555-24.2024","DOIUrl":"10.1523/ENEURO.0555-24.2024","url":null,"abstract":"<p><p>Neurons adapt to chronic activity changes by modifying synaptic properties, including neurotransmitter release. However, whether neuropeptide release via dense core vesicles (DCVs)-a distinct regulated secretory pathway-undergoes similar adaptation remains unclear. Here, we demonstrate that 24-hour action potential blockade leads to significant DCV accumulation in primary mouse cortical neurons of both sexes. Reactivation with action potential trains induced enhanced Ca²⁺-influx and 700% more DCV exocytosis compared to control neurons. Notably, total DCV cargo protein levels were unchanged, while mRNA levels of corresponding genes were reduced. Blocking neurotransmitter release with Tetanus toxin induced DCV accumulation, similar to that induced by network silencing with TTX. Hence, chronic network silencing triggers increased DCV accumulation due to reduced exocytosis during silencing. These accumulated DCVs can be released upon reactivation resulting in a massive potentiation of DCV exocytosis, possibly contributing to homeostatic mechanisms.<b>Significance Statement</b> This study addresses an unexplored area - how dense core vesicles (DCVs) exocytosis adapts to chronic changes in activity - and demonstrates accumulation of DCVs and a massive upregulation of DCV exocytosis in response to 24h inactivity. The potentiation of neuropeptide release might contribute to homeostatic regulation of neuronal networks in the brain.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11964291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656422","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":"Individual Differences in Cognition and Perception Predict Neural Processing of Speech in Noise for Audiometrically Normal Listeners.","authors":"Sana Shehabi, Daniel C Comstock, Kelsey Mankel, Brett M Bormann, Soukhin Das, Hilary Brodie, Doron Sagiv, Lee M Miller","doi":"10.1523/ENEURO.0381-24.2025","DOIUrl":"https://doi.org/10.1523/ENEURO.0381-24.2025","url":null,"abstract":"<p><p>Individuals with normal hearing exhibit considerable variability in their capacity to understand speech in noisy environments. Previous research suggests the cause of this variance may be due to individual differences in cognition and auditory perception. To investigate the impact of cognitive and perceptual differences on speech comprehension, 25 adult human participants with normal hearing completed numerous cognitive and psychoacoustic tasks including the Flanker, Stroop, Trail Making, Reading Span, and temporal fine structure (TFS) tests. They also completed a continuous multi-talker spatial attention task while neural activity was recorded using electroencephalography (EEG). The auditory cortical N1 response was extracted as a measure of neural speech encoding during continuous speech listening using an engineered \"chirped-speech\" (Cheech) stimulus. We compared N1 component morphologies of target and masker speech stimuli to assess neural correlates of attentional gains while listening to concurrently played short story narratives. Performance on cognitive and psychoacoustic tasks were used to predict N1 component amplitude differences between attended and unattended speech using multiple regression. Results show inhibitory control and working memory abilities can predict N1 amplitude differences between the target and masker stories. Interestingly, none of the cognitive and psychoacoustic predictors correlated with behavioral speech-in-noise listening performance in the attention task, suggesting that neural measures may capture different aspects of cognitive and auditory processing compared to behavioral measures alone.<b>Significance statement</b> These findings contribute to our understanding of how cognition affects the neural encoding of auditory selective attention during speech perception. Specifically, our results highlight the complex interplay between cognitive abilities and neural encoding of speech in challenging listening environments with multiple speakers. By incorporating these additional measures of cognition, we can achieve a more comprehensive understanding of an individual's speech perception abilities, even in individuals with normal hearing. This approach could lead to earlier detection of hearing issues and more personalized interventions, ultimately enhancing communication outcomes for those with hearing difficulty.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exposure to acute psychological trauma prior to blast neurotrauma results in alternative behavioral outcomes.","authors":"Jessica Strickler, Susan Murphy, Kathrine Athanasaw, Natalia Bowyer, Pamela J VandeVord","doi":"10.1523/ENEURO.0026-24.2025","DOIUrl":"10.1523/ENEURO.0026-24.2025","url":null,"abstract":"<p><p>Stress is a common occurrence for military personnel. This can include the stress of deployment and active combat. Anxiety is considered a reaction to stress and with anxiety related disorders on the rise, it is imperative that stress be considered a pre-existing condition when studying a number of neurological conditions. To determine the effects of stress on the behavioral outcomes of traumatic brain injury (TBI), we used a 3-day acute unpredictable stress (AUS) model followed by blast induce neurotrauma (BINT) to assessed social anhedonia and anxiety-like behaviors in male and female rats. The animals were divided into 4 groups including an unstressed and uninjured control (Con), stress only animals (AUS), injury only animals (BINT), and animals that received both stress and injury (AUS+BINT). In the males, behavioral tests such as elevated plus and 3-chamber sociability showed that stress plays a dominant role in determining behavioral outcomes after TBI with the AUS+BINT animals behaving more similarly to the AUS animals than the BINT animals. Other tests, such as open field, showed that AUS+BINT had an additive effect on anxiety-like behavior or that pre stress could even have a protective effect as seen in 3-chamber social novelty. Behavioral assessment of female animals showed that AUS+BINT had the opposite effect than it did on the males in both 3-chamber sociability and 3-chamber social novelty, while the open field results were similar to the males. This study shows that neurological changes driven by stress have an effect on the behavioral outcomes of BINT.<b>Significance Statement</b> It has been well established that exposure to even acutely stressful situations can cause long lasting neurological and behavioral changes. While many studies have focused on the neuropathological and psychological aspects of TBI and stress separately, the relationship between the two is understudied. Current preclinical models of TBI actively attempt to minimize the animal's exposure to stress to prevent any stress-induced neurological changes from interfering with TBI-related outcomes. Here we demonstrate that, by not factoring in stress-induced neurological changes, we are limiting the clinical relevancy of the TBI model given that stress is an everyday factor in human populations.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647723","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":"Astrocytes in the External Globus Pallidus Selectively Represent Routine Formation During Repeated Reward-Seeking in Mice.","authors":"Minsu Abel Yang, Shinwoo Kang, Sa-Ik Hong, Jeyeon Lee, Nicholas L Bormann, Sang Wan Lee, Doo-Sup Choi","doi":"10.1523/ENEURO.0552-24.2025","DOIUrl":"10.1523/ENEURO.0552-24.2025","url":null,"abstract":"<p><p>The external globus pallidus (GPe) is a central part of the basal ganglia indirect pathway implicated in movement and decision-making. As a hub connecting the dorsal striatum and subthalamic nucleus (STN), the GPe guides repetitive and routine behaviors. However, it remains unknown how diverse GPe cells engage in routine formation while learning action sequences in repetitive reward-seeking conditioning. Here, in male mice, we investigated the Ca²⁺ dynamics of two GPe cell types, astrocytes and parvalbumin-expressing neurons, during routine formation. Our findings show that the dynamics of GPe astrocytes may be involved in action sequence refinement, a characteristic potentially contributing to more efficient reward-seeking behavior.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11913404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540598","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":"Prenatal ethanol exposure results in cell-type, age, and sex-dependent differences in the neonatal striatum that coincide with early motor deficits.","authors":"Adelaide R Tousley, Ilana Deykin, Betul Koc, Pamela Wl Yeh, Hermes H Yeh","doi":"10.1523/ENEURO.0448-24.2025","DOIUrl":"10.1523/ENEURO.0448-24.2025","url":null,"abstract":"<p><p>Delayed motor development is an early clinical sign of Fetal Alcohol Spectrum Disorders (FASD). However, changes at the neural circuit level that underlie early motor differences are underexplored. The striatum, the principal input nucleus of the basal ganglia, plays an important role in motor learning in adult animals, and the maturation of the striatal circuit has been associated with the development of early motor behaviors. Here, we briefly exposed pregnant C57BL/6 dams to ethanol (5% w/w) in a liquid diet on embryonic days (E)13.5-16.5, and assessed the mouse progeny using a series of 9 brief motor behavior tasks on postnatal days (P)2-14. Live brain slices were then obtained from behaviorally-tested mice for whole cell-voltage and current clamp electrophysiology to assess GABAergic/glutamatergic synaptic activity, and passive/active properties in two populations of striatal neurons: GABAergic interneurons and spiny striatal projection neurons. Electrophysiologically-recorded spiny striatal projection neurons were also filled intracellularly with biocytin for <i>post-hoc</i> analysis of dendritic morphology. We found that prenatal ethanol exposure resulted in developmental motor delays that were more severe in male mice and coincided with sex-dependent differences in the maturation of striatal neurons. Our findings indicate that prenatal ethanol exposure results in dynamic morphological and functional changes to the developmental trajectories of striatal neurons commensurate with the development of motor behaviors that differ between male and female mice.<b>Significance Statement</b> Developmental differences in motor behaviors are an early clinical sign of Fetal Alcohol Spectrum Disorders (FASD) but the neural circuit level changes that contribute to these differences have not yet been determined. Here we demonstrate that a brief binge exposure to ethanol alters the motor development of neonatal mice in a sex-dependent manner, and identify concurrent differences in the functional, synaptic and morphological development of striatal GABAergic interneurons and medium spiny striatal projection neurons. These data suggest that altered development of striatal neurons may contribute to differences in early motor development observed in individuals with FASD.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630295","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":"Correlated and Anticorrelated Binocular Disparity Modulate GABA+ and Glutamate/Glutamine Concentrations in the Human Visual Cortex.","authors":"Jacek Matuszewski, Ivan Alvarez, William T Clarke, Andrew J Parker, Holly Bridge, I Betina Ip","doi":"10.1523/ENEURO.0355-24.2025","DOIUrl":"10.1523/ENEURO.0355-24.2025","url":null,"abstract":"<p><p>Binocular disparity is used for perception and action in three dimensions. Neurons in the primary visual cortex respond to binocular disparity in random dot patterns, even when the contrast is inverted between eyes (false depth cue). In contrast, neurons in the ventral stream largely cease to respond to false depth cues. This study evaluated whether GABAergic inhibition is involved in suppressing false depth cues in the human ventral visual cortex. We compared GABAergic inhibition (GABA+) and glutamatergic excitation (Glx) during the viewing of correlated and anticorrelated binocular disparity in 18 participants using single-voxel proton magnetic resonance spectroscopy. Measurements were taken from the early visual cortex (EVC) and the lateral occipital cortex (LO). Three visual conditions were presented per voxel location: correlated binocular disparity, anticorrelated binocular disparity, or a blank gray screen with a fixation cross. To identify differences in neurochemistry, GABA+ or Glx levels were compared across viewing conditions. In EVC, correlated disparity increased Glx over anticorrelated and rest conditions, also mirrored in the Glx/GABA+ ratio. In LO, anticorrelated disparity decreased GABA+ and increased Glx. The Glx/GABA+ ratio showed increased excitatory over inhibitory drive to anticorrelated disparity in LO. Glx during viewing of anticorrelation in LO was predictive of object-selective BOLD activity in the same region. We provide evidence that early and ventral visual cortices change GABA+ and Glx concentrations during presentation of correlated and anticorrelated disparity, suggesting a contribution of cortical excitation and inhibition to disparity selectivity.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11913401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499869","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":"Phosphorylation of NLGN4X Regulates Spinogenesis and Synaptic Function.","authors":"Alexander W Lehr, Thien A Nguyen, Wenyan Han, Eunhye Hong, John D Badger, Wei Lu, Katherine W Roche","doi":"10.1523/ENEURO.0278-23.2025","DOIUrl":"10.1523/ENEURO.0278-23.2025","url":null,"abstract":"<p><p>Neuroligins (NLGNs) are a family of postsynaptic adhesion molecules that bind to their presynaptic partners, neurexins, facilitating the formation and maintenance of synapses. In humans, there are five genes encoding NLGNs (<i>NLGN1-3</i>, <i>NLGN4X</i>, and <i>NLGN4Y</i>), with <i>NLGN1-3</i> having highly conserved counterparts in rodents, allowing these genes to be studied with high confidence of translational validity in mouse models. Human NLGN4X and 4Y were often assumed to serve similar functions because they share a 97% sequence homology, whereas mouse NLGN4-like is quite divergent. Many NLGN-mediated synaptic effects are modulated through post-translation modifications, which exert temporal and spatial control. In this report, we characterize a conserved phosphorylation site, serine 712, on NLGN4X and 4Y. Despite serine 712 being located in a highly conserved region between NLGN4X and 4Y, we observed kinase specificity. PKA exclusively phosphorylates NLGN4X S712, whereas Cdk5 phosphorylates S712 on both NLGN4X and 4Y. NLGN4X S712 phosphorylation regulated spine density, with phosphorylation reducing mature mushroom spines and unphosphorylated S712 increasing spines and enhancing miniature excitatory postsynaptic current frequency.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11913403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540613","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":"Cocaine Self-Administration Increases Impulsive Decision-Making in Low-Impulsive Rats Associated with Impaired Functional Connectivity in the Mesocorticolimbic System.","authors":"Hui Shen, Zilu Ma, Emma Hans, Ying Duan, Guo-Hua Bi, Yurim C Chae, Robbie Y Kuang, Zheng-Xiong Xi, Yihong Yang","doi":"10.1523/ENEURO.0408-24.2025","DOIUrl":"10.1523/ENEURO.0408-24.2025","url":null,"abstract":"<p><p>Impulsivity is often considered a risk factor for drug addiction; however, not all evidence supports this view. In the present study, we used a food reward delay-discounting task (DDT) to categorize rats as low-, middle-, and high-impulsive but failed to find any difference among these groups in the acquisition and maintenance of cocaine self-administration (SA), regardless of electrical footshock punishment. Additionally, there were no group differences in locomotor responses to acute cocaine in rats with or without a history of cocaine SA. Unexpectedly, chronic cocaine SA selectively increased impulsive choice in low-impulsive rats. Resting-state fMRI analysis revealed a positive correlation between impulsivity and cerebral blood volume in the midbrain, thalamus, and auditory cortex. Using these three regions as seeds, we observed a negative correlation between impulsivity and functional connectivity between the midbrain and frontal cortex, as well as between the thalamus and frontal cortex (including the orbitofrontal, primary, and parietal cortices) in low-impulsive rats. These correlations were attenuated following chronic cocaine SA. RNAscope in situ hybridization assays revealed a significant reduction in dopamine (DA) D₁, D₂, and D₃ receptor mRNA expression in the corticostriatal regions of low-impulsive rats after cocaine SA. Our findings challenge the widely held view that impulsivity is a vulnerability factor for cocaine use disorder. Instead, chronic cocaine use appears to selectively increase impulsive choice decision-making in normally low-impulsive rats, associated with reduced functional connectivity and DA receptor expression in the mesocorticolimbic DA network.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11913322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540611","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":"Neuroanatomical Mapping of Gerbil Corticostriatal and Thalamostriatal Projections Reveals the Parafascicular Nucleus as a Relay for Vestibular Information to the Entire Striatum.","authors":"Jared B Smith, Sean S Hong, Damian J Murphy, Evelynne Dangcil, Jacqueline Nacipucha, Aaron Tucker, Nicolas L Carayannopoulos, Mina Beshy, Shrivaishnavi Chandrasekar, Eran Peci, Matthew Y Kiel, P Ashley Wackym, Justin D Yao, Todd M Mowery","doi":"10.1523/ENEURO.0246-24.2025","DOIUrl":"10.1523/ENEURO.0246-24.2025","url":null,"abstract":"<p><p>The striatum is the primary input nucleus of the basal ganglia, integrating a dense plexus of inputs from the cerebral cortex and thalamus to regulate action selection and learning. Neuroanatomical mapping of the striatum and its subcompartments has been carried out extensively in rats and mice, nonhuman primates, and cats allowing comparative neuroanatomy studies to derive heuristics about striatal composition and function. Here, we systematically map corticostriatal topography from motor, somatosensory, auditory, and visual cortices as well as thalamostriatal parafascicular (PfN) inputs in the Mongolian gerbil. We also map a pathway reported in mice from medial vestibular nucleus to the PfN that could convey vestibular information to the striatum. Our findings align with those of similar studies in other rodents, indicating homologous neuroanatomical connectivity patterns within the corticostriatal projectome across Rodentia. We observed corticostriatal peaks of dense labeling for each input with a diffuse projection throughout striatal subregions from each cortical region, suggesting a global integration of all cortical information by the striatum. Thalamostriatal projections from PfN covered most of the striatum with a peak of PfN-specific compartmentalized labeling similar to other sensory and motor systems. We also confirm the connection from the medial vestibular nucleus to PfN thalamus, indicating that vestibular information may be widely integrated throughout the striatum. The findings build upon our body of knowledge on striatal connectivity across mammalian species and provide a foundation for striatal research focusing on vestibulothalamostriatal circuits in Rodentia.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11913323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425192","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":"Heroin Regulates the Voltage-Gated Sodium Channel Auxiliary Subunit, SCN1b, to Modulate Nucleus Accumbens Medium Spiny Neuron Intrinsic Excitability and Cue-Induced Heroin Seeking.","authors":"Ethan M Anderson, Evgeny Tsvetkov, Daniel Wood, Rose Marie Akiki, Karim Al Hasanieh, Lauren M McCue, Makoto Taniguchi, Antonieta Lavin, Christopher W Cowan","doi":"10.1523/ENEURO.0017-25.2025","DOIUrl":"10.1523/ENEURO.0017-25.2025","url":null,"abstract":"<p><p>Self-administration of addictive substances like heroin can couple the rewarding/euphoric effects of the drug with drug-associated cues, and opioid cue reactivity contributes to relapse vulnerability in abstinent individuals recovering from an opioid use disorder (OUD). Opioids are reported to alter the intrinsic excitability of medium spiny neurons (MSNs) in the nucleus accumbens (NAc), a key brain reward region linked to drug seeking, but how opioids alter NAc MSN neuronal excitability and the impact of altered MSN excitability on relapse-like opioid seeking remain unclear. Here, we discovered that self-administered, but not experimenter-administered, heroin reduced NAc protein levels of the voltage-gated sodium channel auxiliary subunit, SCN1b, in male and female rats. Viral-mediated reduction of NAc SCN1b increased the intrinsic excitability of MSNs, but without altering glutamatergic and GABAergic synaptic transmission. While reducing NAc SCN1b levels had no effect on acquisition of heroin self-administration or extinction learning, we observed a significant increase in cue-reinstated heroin seeking, suggesting that NAc SCN1b normally limits cue-reinstated heroin seeking. We also observed that NAc SCN1b protein levels returned to baseline following heroin self-administration, home-cage abstinence, and extinction training, suggesting that the noted reduction of NAc SCN1b during acquisition of heroin self-administration likely enhances MSN excitability and the strength of heroin-cue associations formed during active heroin use. As such, enhancing NAc SCN1b function might mitigate opioid cue reactivity and a return to active drug use in individuals suffering from OUD.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11913320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413723","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}