eNeuro最新文献

{"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":"https://doi.org/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 sub compartments has been carried out extensively in rats and mice, non-human 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.<b>Significance statement</b> In this study, systematic mapping of the projections to striatum from motor, somatosensory, auditory, and visual cortices in Mongolian gerbil reveal commonalities with rodents. Principally, while some areas receive compartmentalized innervation from specific modalities, there also exists a global interspersed plexus of integrating inputs from each cortical area to each striatal subregion. Additionally, we also demonstrate a clear thalamostriatal innervation from parafascicular thalamus (PfN), that is homologous to other rodents and primates. Finally, we confirm a pathway from the medial vestibular nucleus to PfN thalamus that could broadly convey vestibular information across the striatum. Our results reveal common principles in neuroanatomical connectivity across another mammalian species and provide an anatomical map to guide future vestibular striatal studies in gerbils and other animal models.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding Visual Spatial Attention Control.","authors":"Sreenivasan Meyyappan, Abhijit Rajan, Qiang Yang, George R Mangun, Mingzhou Ding","doi":"10.1523/ENEURO.0512-24.2025","DOIUrl":"10.1523/ENEURO.0512-24.2025","url":null,"abstract":"<p><p>In models of visual spatial attention control, it is commonly held that top-down control signals originate in the dorsal attention network, propagating to the visual cortex to modulate baseline neural activity and bias sensory processing. However, the precise distribution of these top-down influences across different levels of the visual hierarchy is debated. In addition, it is unclear whether these changes in baseline neural activity directly translate into improved performance. We analyzed attention-related baseline activity during the anticipatory period of a trial-by-trial voluntary spatial attention task, using two independent fMRI datasets, and two different analytic approaches. First, as in prior studies, univariate analysis showed that covert attention significantly enhanced baseline neural activity in higher-order visual areas contralateral to the attended visual hemifield, while effects in lower-order visual areas (e.g., V1) were weaker and more variable. Second, in contrast, multivariate pattern analysis (MVPA) revealed significant decoding of attention conditions across all visual cortical areas, with lower-order visual areas exhibiting higher decoding accuracies than higher-order areas. Third, decoding accuracy, rather than the magnitude of univariate activation, was a better predictor of a subject's stimulus discrimination performance. Finally, the MVPA results were replicated across two experimental conditions, where the direction of spatial attention was either externally instructed by a cue or based on the participants free choice decision about where to attend. Together, these findings offer new insights into the extent of attentional biases in the visual hierarchy under top-down control, and how these biases influence both sensory processing and behavioral performance.<b>Significance Statement</b> Attention can be deployed in advance of stimulus processing. Understanding how top-down control of attention facilitates the processing of the attended stimuli and enhances task performance has remained a longstanding question in attention research. Here, applying multivariate pattern analysis (MVPA) to fMRI data, we showed that throughout the entire visual hierarchy including the primary visual cortex, there exist distinct neural representations for different attended information in anticipatory visual spatial attention, and the distinctiveness of these neural representations is positively associated with behavioral performance. Importantly, the MVPA findings were consistent across two experimental conditions where the direction of spatial attention was driven either by external instructions or from purely internal decisions.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413612","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":"A common stay-on-goal mechanism in anterior cingulate cortex for information and effort choices.","authors":"Valeria V González, Melissa Malvaez, Alex Yeghikian, Sydney Wissing, Melissa Sharpe, Kate M Wassum, Alicia Izquierdo","doi":"10.1523/ENEURO.0454-24.2025","DOIUrl":"10.1523/ENEURO.0454-24.2025","url":null,"abstract":"<p><p>Humans and non-humans alike often make choices to gain information, even when the information cannot be used to change the outcome. Prior research has shown the anterior cingulate cortex (ACC) is important for evaluating options involving reward-predictive information. Here we studied the role of ACC in information choices using optical inhibition to evaluate the contribution of this region during specific epochs of decision making. Rats could choose between an uninformative option followed by a cue that predicted reward 50% of the time vs. a fully informative option that signaled outcomes with certainty, but was rewarded only 20% of the time. Reward seeking during the informative S+ cue decreased following ACC inhibition, indicating a causal contribution of this region in supporting reward expectation to a cue signaling reward with certainty. Separately in a positive control experiment and in support of a known role for this region in sustaining high-effort behavior for preferred rewards, we observed reduced lever presses and lower breakpoints in effort choices following ACC inhibition. The lack of changes in reward latencies in both types of decisions indicate the motivational value of rewards remained intact, revealing instead a common role for ACC in maintaining persistence toward certain and valuable rewards.<b>Significance Statement</b> We often make choices to gain information, even when the information cannot be used to change the outcome. Here we investigated the precise timing of the role of the anterior cingulate cortex (ACC) in decisions that involve seeking certain versus uncertain rewards. By optically inhibiting ACC neurons, we demonstrate that this region is crucial for maintaining persistence toward rewards signaled with certainty, without altering the motivational value of the reward itself. In a positive control experiment, we also confirm that ACC is important in effort-based choice. The findings reveal a common role for ACC in maintaining persistence toward certain and valuable rewards, necessary for making optimal decisions. These results have implications for understanding psychiatric disorders involving maladaptive reward-seeking behavior.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413611","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":"Facial Paralysis Algorithm: a tool to infer facial paralysis in awake mice.","authors":"Elías Perrusquia Hernández, Diego Israel Villeda Arias, Claudia Daniela Montes Ángeles, Rey David Andrade González, Joel Lomelí González, Isaac Obed Pérez-Martínez","doi":"10.1523/ENEURO.0384-24.2025","DOIUrl":"https://doi.org/10.1523/ENEURO.0384-24.2025","url":null,"abstract":"<p><p>Facial paralysis is characterized by an injury to the facial nerve, causing the loss of the functions of the structures that it innervates, as well as changes in the motor cortex. Current models have some limitations for the study of facial paralysis, such as movement restriction, the absence of studying awake animals in behavioral contexts, and the lack of a model that fully evaluates facial movements. The development of an algorithm capable of automatically inferring facial paralysis and overcoming the existing limitations is proposed in this work. In C57/BL6J mice, we produced both irreversible and reversible facial paralysis. Video recordings were made of the faces of paralyzed mice to develop the algorithm for detecting facial paralysis applied to mice, which allows us to predict the presence of reversible and irreversible facial paralysis automatically. At the same time, the algorithm was used to track facial movement during gustatory stimulation, and extracellular electrophysiological recordings in the anterolateral motor cortex. In the basal state, mice can make facial expressions, whereas the algorithm can detect this movement. Simultaneously, such movement is correlated with the activation in the anterolateral motor cortex. In the presence of facial paralysis, the algorithm cannot detect movement. Furthermore, it predicts that the condition exists, and the neuronal activity in the cortex is affected with respect to the evolution of facial paralysis. This way, we conclude that the facial paralysis algorithm applied to mice allows for inferring the presence of experimental facial paralysis and its neuronal correlates for further studies.<b>Significance Statement</b> Recording the faces of mice can help predict facial paralysis unbiasedly and identify the presence of a reduction in facial movement associated with injury to the facial nerve. It can also be used to study facial movements, like facial expressions, and their neural correlates in cortical and subcortical strata. This will not only allow a deep understanding of the magnitude of the effects that facial paralysis can produce at the peripheral and central nervous system levels but also inspire further research and the search for potential treatments.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413614","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":"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":"https://doi.org/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.<b>Significance Statement</b> Opioid use disorder (OUD) is a chronic, relapsing disease characterized by excessive craving. Here we found that repeated heroin self-administration reduced the expression of the sodium channel subunit, SCN1b, in the nucleus accumbens, a brain area important for reward signaling and addiction. We show here that reducing SCN1b increased excitability of NAc neurons and increased relapse-like drug seeking in a rodent model of opioid craving. The discovery of this novel mechanism of opioid action in the brain could help lead to future treatments for patients that suffer from OUD.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Dual Role of A2aR in Neuroinflammation: Modulating Microglial Polarization in White Matter Lesions.","authors":"Chang Cheng, Wenchao Cheng, Yuhan Wang, Xiuying Chen, Lan Zhang, Yi Li, Fa Shen, Dezhi Yuan, Pian Hong, Wen Huang","doi":"10.1523/ENEURO.0579-24.2025","DOIUrl":"https://doi.org/10.1523/ENEURO.0579-24.2025","url":null,"abstract":"<p><p>Neuroinflammation has been widely recognized as the primary pathophysiological mechanism underlying ischemic white matter lesions (IWML) in chronic cerebral hypoperfusion (CCH), with microglia serving as the principal effector cells. A2aR, an important adenosine receptor, exhibits a dual role in neuroinflammation by modulating both pro-inflammatory and anti-inflammatory responses, particularly through its regulation of microglial polarization. This study aimed to investigate the specific functions and mechanisms of A2aR in neuroinflammation. The findings revealed that A2aR initially exerted a pro-inflammatory role in the CCH model, transitioning to an anti-inflammatory role in later stages by regulating the phenotypic transformation of microglia. Further analyses using CoIP-MS, in situ proximity ligation assay, Alphafold protein structure prediction, [³⁵S]GTPγS Binding Assay and Nano-Bit technology demonstrated that A2aR formed heteromers with mGluR5 during the early stage of CCH under high glutamate conditions, promoting the polarization of microglia towards a pro-inflammatory phenotype. In contrast, during later stages characterized by low glutamate levels, A2aR predominantly existed as a monomer, facilitating microglial polarization towards an anti-inflammatory phenotype. Our findings indicate that elevated glutamate levels drive the formation of A2aR-mGluR5 heteromers, contributing to neuroinflammation by promoting pro-inflammatory microglial polarization in CCH white matter. Conversely, under low glutamate conditions, A2aR primarily functions in its monomeric form, favoring an anti-inflammatory microglial phenotype and exerting a protective effect. This study elucidates the mechanism by which A2aR mediates microglial phenotypic transformation and participates in neuroinflammation under CCH. It also identifies A2aR as a potential therapeutic target for the treatment of IWML.<b>Significance Statement</b> Neuroinflammation of white matter is widely recognized as the primary pathophysiological mechanism associated with vascular dementia (VaD) in middle-aged and elderly individuals.A2aR, a crucial adenosine receptor, exhibits a dual role in neuroinflammation by modulating both proinflammatory and anti-inflammatory responses, particularly in relation to microglia polarization. The objective of this study is to investigate the specific functions and mechanisms of A2aR in neuroinflammation. The results indicate that elevated glutamate levels facilitate the formation of A2aR-mGluR5 heteromers, thereby promoting the polarization of microglia towards a pro-inflammatory phenotype, which contributes to neuroinflammation in CCH white matter. Conversely, under conditions of low glutamate, A2aR predominantly exists in monomeric form, which favors the polarization of microglia towards an anti-inflammatory phenotype, thereby exerting a protective effect.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413727","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":"Functional Connectivity of the Scene Processing Network at Rest Does Not Reliably Predict Human Behavior on Scene Processing Tasks.","authors":"David M Watson, Timothy J Andrews","doi":"10.1523/ENEURO.0375-24.2024","DOIUrl":"10.1523/ENEURO.0375-24.2024","url":null,"abstract":"<p><p>The perception of scenes is associated with processing in a network of scene-selective regions in the human brain. Prior research has identified a posterior-anterior bias within this network. Posterior scene regions exhibit preferential connectivity with early visual and posterior parietal regions, indicating a role in representing egocentric visual features. In contrast, anterior scene regions demonstrate stronger connectivity with frontoparietal control and default mode networks, suggesting a role in mnemonic processing of locations. Despite these findings, evidence linking connectivity in these regions to cognitive scene processing remains limited. In this preregistered study, we obtained cognitive behavioral measures alongside resting-state fMRI data from a large-scale public dataset to investigate interindividual variation in scene processing abilities relative to the functional connectivity of the scene network. Our results revealed substantial individual differences in scene recognition, spatial memory, and navigational abilities. Resting-state functional connectivity reproduced the posterior-anterior bias within the scene network. However, contrary to our preregistered hypothesis, we did not observe any consistent associations between interindividual variation in this connectivity and behavioral performance. These findings highlight the need for further research to clarify the role of these connections in scene processing, potentially through assessments of functional connectivity during scene-relevant tasks or in naturalistic conditions.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11820959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074264","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":"FAST: Fast, Free, Consistent, and Unsupervised Oligodendrocyte Segmentation and Tracking System.","authors":"Eunchan Bae, Gregory E Perrin, Virgilio Gonzenbach, Jennifer L Orthmann-Murphy, Russell T Shinohara","doi":"10.1523/ENEURO.0025-24.2024","DOIUrl":"10.1523/ENEURO.0025-24.2024","url":null,"abstract":"<p><p>To develop reparative therapies for neurological disorders like multiple sclerosis (MS), we need to better understand the physiology of loss and replacement of oligodendrocytes, the cells that make myelin and are the target of damage in MS. <i>In vivo</i> two-photon fluorescence microscopy allows direct visualization of oligodendrocytes in the intact brain of transgenic mouse models, promising a deeper understanding of the longitudinal dynamics of replacing oligodendrocytes after damage. However, the task of tracking the fate of individual oligodendrocytes requires extensive effort for manual annotation and is especially challenging in three-dimensional images. While several models exist for annotating cells in two-dimensional images, few models exist to annotate cells in three-dimensional images and even fewer are designed for tracking cells in longitudinal imaging. Notably, existing options often come with a substantial financial investment, being predominantly commercial or confined to proprietary software. Furthermore, the complexity of processes and myelin formed by individual oligodendrocytes can result in the failure of algorithms that are specifically designed for tracking cell bodies alone. Here, we propose a fast, free, consistent, and unsupervised beta-mixture oligodendrocyte segmentation system (FAST) that is written in open-source software, and can segment and track oligodendrocytes in three-dimensional images over time with minimal human input. We showed that the FAST model can segment and track oligodendrocytes similarly to a blinded human observer. Although FAST was developed to apply to our studies on oligodendrocytes, we anticipate that it can be modified to study four-dimensional <i>in vivo</i> data of any brain cell with associated complex processes.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11820958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946586","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":"Growth Hormone Alters Remapping in the Hippocampal Area CA1 in a Novel Environment.","authors":"Kamilla G Haugland, Sondre Valentin Jordbræk, Erik Knutsen, Kirsten B Kjelstrup, Vegard H Brun","doi":"10.1523/ENEURO.0237-24.2024","DOIUrl":"10.1523/ENEURO.0237-24.2024","url":null,"abstract":"<p><p>Growth hormone (GH) is a neuromodulator that binds to receptors in the hippocampus and alters synaptic plasticity. A decline in GH levels is associated with normal aging, stress, and disease, and the mechanisms proposed involve the hippocampal circuit plasticity. To see how GH affects the hippocampal neural code, we recorded single neurons in the CA1 region of male Long-Evans rats with locally altered GH levels. Rats received injections of adeno-associated viruses into the hippocampus to make the cells overexpress either GH or an antagonizing mutated GH (aGH). Place cells were recorded in both familiar and novel environments to allow the assessment of pattern separation in the neural representations termed remapping. All the animals showed intact and stable place fields in the familiar environment. In the novel environment, aGH transfection increased the average firing rate, peak rate, and information density of the CA1 place fields. The tendency of global remapping increased in the GH animals compared with the controls, and only place cells of control animals showed significant rate remapping. Our results suggest that GH increases hippocampal sensitivity to novel information. Our findings show that GH is a significant neuromodulator in the hippocampus affecting how place cells represent the environment. These results could help us to understand the mechanisms behind memory impairments in GH deficiency as well as in normal aging.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11814925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122545","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":"Detection of mitotic neuroblasts provides additional evidence of steady state neurogenesis in the adult small intestinal myenteric plexus.","authors":"Anastazja M Gorecki, Jared Slosberg, Su Min Hong, Philippa Seika, Srinivas Puttapaka, Blake Migden, Anton Gulko, Alpana Singh, Chengxiu Zhang, Rohin Gurumurthy, Subhash Kulkarni","doi":"10.1523/ENEURO.0005-24.2025","DOIUrl":"10.1523/ENEURO.0005-24.2025","url":null,"abstract":"<p><p>Maintenance of normal structure of the enteric nervous system (ENS), which regulates key gastrointestinal functions, requires robust homeostatic mechanisms, since by virtue of its location within the gut wall, the ENS is subject to constant mechanical, chemical, and biological stressors. Using transgenic and thymidine analogue-based experiments, we previously discovered that neuronal turnover - where continual neurogenesis offsets ongoing neuronal loss at steady state - represents one such mechanism. Although other studies confirmed that neuronal death continues into adulthood in the myenteric plexus of the enteric nervous system (ENS), the complicated nature of thymidine analogue presents challenges in substantiating the occurrence of adult neurogenesis. Therefore, it's vital to employ alternative, well-recognized techniques to substantiate the existence of adult enteric neurogenesis in the healthy gut. Here, by using established methods of assessing nuclear DNA content and detecting known mitotic marker phosphor-histone H3 (pH3) in Hu⁺ adult ENS cells, we show that ∼10% of adult small intestinal myenteric Hu⁺ cells in mice, and ∼20% of adult human small intestinal myenteric Hu⁺ cells show evidence of mitosis and hence are cycling neuroblasts. We observe that proportions of Hu⁺ cycling neuroblasts in the adult murine ENS neither vary with ganglia size, nor do they differ significantly between two intestinal regions - duodenum and ileum, or between sexes. Confocal microscopy provides further evidence of cytokinesis in Hu⁺ cells. The presence of a significant population of cycling neuroblasts in adult ENS provide further evidence of steady state neurogenesis in the adult ENS.<b>Significance statement</b> Using 3-dimensional confocal microscopy, immunohistochemical detection of cell cycle marker phosphor-Histone H3, and DNA content assessments using flow cytometry in Hu+ cells from adult small intestinal murine myenteric plexus, we show that ∼10% of myenteric Hu+ cells in adult gut are mitotic neuroblasts, whose proportional representation does not significantly differ between sexes or small intestinal regions. We further test and observe mitotic marker pH3 also immunolabels ∼23% of adult human myenteric Hu+ cells suggesting that presence of mitotic neuroblasts also extends to the adult human gut. These data further evidence of steady state adult enteric neurogenesis in the healthy gut and provide important cellular details in understanding how precursor cells continually generate large numbers of adult neurons in healthy gut.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398624","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}