Journal of Neuroscience最新文献

{"title":"A New Optogenetic Tool to Investigate the Role of Dopamine Signaling in the Basal Ganglia.","authors":"Gabriel S Rocha,Marco Aurelio M Freire","doi":"10.1523/jneurosci.0294-25.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.0294-25.2025","url":null,"abstract":"","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"24 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144320089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EEG correlates of active removal from working memory.","authors":"Jiangang Shan, Bradley R Postle","doi":"10.1523/JNEUROSCI.2414-24.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.2414-24.2025","url":null,"abstract":"<p><p>The removal of no-longer-relevant information from visual working memory (WM) is important for the functioning of WM, given its severe capacity limitation. Previously, with an \"ABC-retrocuing\" WM task, we have shown that removing information can be accomplished in different ways: by simply withdrawing attention from the newly irrelevant memory item (IMI; i.e., via \"passive removal\"); or by or \"actively\" removing the IMI from WM (Shan and Postle, 2022). Here, to investigate the neural mechanisms behind active removal, we recorded electroencephalogram (EEG) signals from human subjects (both sexes) performing the ABC-retrocuing task. Specifically, we tested the hijacked adaptation model, which posits that active removal is accomplished by a top-down-triggered down-modulation of the gain of perceptual circuits, such that sensory channels tuned to the to-be-removed information become less sensitive. Behaviorally, analyses revealed that, relative to passive removal, active removal produced a decline in the familiarity landscape centered on the IMI. Neurally, we focused on two epochs of the task, corresponding to the triggering, and to the consequence, of active removal. With regard to triggering, we observed a stronger anterior-to-posterior traveling wave for active versus passive removal. With regard to the consequence(s) of removal, the response to a task-irrelevant \"ping\" was reduced for active removal, as assessed with ERP, suggesting that active removal led to decreased excitability in perceptual circuits centered on the IMI.<b>Significance Statement</b> The removal of no-longer-relevant information from working memory is critical for the flexible control of behavior. However, to our knowledge, the only explicit accounts of this operation describe the simple withdrawal of attention from that information (i.e., \"passive removal\"). Here, with measurements of behavior and electroencephalography (EEG), we provide evidence for a specific mechanism for the active removal of information from WM-hijacked adaptation-via the top-down triggering of an adaptation-like down-regulation of gain of the perceptual circuits tuned to the to-be-removed information. These results may have implications for disorders of mental health, including rumination, intrusion of negative thoughts, and hallucination.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Attentional precursors of errors predict error-related brain activity.","authors":"Martin E Maier, Marco Steinhauser","doi":"10.1523/JNEUROSCI.0757-25.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.0757-25.2025","url":null,"abstract":"<p><p>The error negativity or error-related negativity (Ne/ERN), a correlate of errors in choice tasks, is related to post-error adjustments indicating that it signals the need for behavioral adjustments following errors. However, little is known how the error monitoring system selects appropriate post-error adjustments for a given error to ensure that future errors are effectively prevented. This could be achieved by monitoring error precursors indicating potential error sources and then scale the Ne/ERN according to the strength of the error precursor upon error occurrence. We isolated such an error precursor in alpha oscillations and tested whether it predicts the size of the Ne/ERN. 28 Participants (23 female, 5 male) had to classify a target in one hemifield but ignore a distractor in the opposite hemifield. Because responding to the distractor always led to an error, misallocating spatial attention to the distractor as reflected in posterior alpha was a viable error precursor in this paradigm. We found that an alpha asymmetry reversal indicated a shift of spatial attention to the distractor on error trials and predicted the Ne/ERN on a single-trial level. The Ne/ERN in turn predicted alpha asymmetry on the next trial indicating a shift of spatial attention away from the distractor. This is consistent with the idea that the error monitoring system scales the Ne/ERN according to the strength of error precursors to select appropriate post-error adjustments of behavior.<b>Significance Statement</b> This study reports evidence that the error monitoring system uses misallocation of spatial attention to distracting information as an error precursor to scale error signals in the brain. This ensures that error signals convey information about the type and strength of behavioral post-error adjustments that are necessary for a given error. The idea of monitoring error precursors that reflect specific error sources significantly extends existing theories of error monitoring mechanisms in the brain.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased neuronal expression of the early endosomal adaptor APPL1 replicates Alzheimer's Disease-related endosomal and synaptic dysfunction with cholinergic neurodegeneration.","authors":"Ying Jiang, Kuldeep Sachdeva, Chris N Goulbourne, Martin J Berg, James Peddy, Philip H Stavrides, Anna Pensalfini, Monika Pawlik, Sandeep Malampati, Lauren Whyte, Balapal S Basavarajappa, Subbanna Shivakumar, Cynthia Bleiwas, John F Smiley, Paul M Mathews, Ralph A Nixon","doi":"10.1523/JNEUROSCI.2331-24.2025","DOIUrl":"10.1523/JNEUROSCI.2331-24.2025","url":null,"abstract":"<p><p>Endosomal system dysfunction within neurons is a prominent early feature of Alzheimer's disease (AD) pathology. Multiple AD risk factors are regulators of endocytosis and are known to cause hyper-activity of the early-endosome small GTPase rab5, resulting in neuronal endosomal pathway disruption and cholinergic neurodegeneration. Adaptor protein containing Pleckstrin homology domain, Phosphotyrosine binding domain, Leucine zipper motif (APPL1), an important rab5 effector protein and signaling molecule, has been shown <i>in vitro</i> to interface between endosomal and neuronal dysfunction through a rab5-activating interaction with the BACE1-generated C-terminal fragment of amyloid precursor protein (APP-βCTF), a pathogenic APP fragment generated within endosomal compartments. To understand the contribution of APPL1 to AD-related endosomal dysfunction in vivo, we generated a transgenic mouse model over-expressing human APPL1 within neurons (Thy1-APPL1). Strongly supporting the important endosomal regulatory roles of APPL1 and their relevance to AD etiology, Thy1-APPL1 mice (both sexes) develop enlarged neuronal early endosomes and increased synaptic endocytosis due to increased rab5 activation. We demonstrated pathophysiological consequences of APPL1 overexpression, including functional changes in hippocampal long-term potentiation (LTP) and long-term depression (LTD), degeneration of large projection cholinergic neurons of the basal forebrain, and impaired hippocampal-dependent memory. Our evidence shows that neuronal APPL1 elevation modeling its functional increase in the AD brain induces a cascade of AD-related pathological effects within neurons, including early endosome anomalies, synaptic dysfunction, and selective neurodegeneration. Our in vivo model highlights the contributions of APPL1 to the pathobiology and neuronal consequences of early endosomal pathway disruption and its potential value as a therapeutic target.<b>Significance Statement</b> Neuronal endosome dysfunction appears early in Alzheimer's disease (AD) and is linked to memory loss. Genes and risk factors associated with AD often increase rab5 activity, a protein that disrupts endosomal signalling when hyperactivated. APPL1, a key rab5 partner, worsens this dysfunction via its interaction with APP-βCTF, a protein fragment associated with AD. To explore APPL1's role, we created a genetically modified mouse that overexpresses APPL1 in neurons. This model provides the first in vivo evidence that APPL1 overexpression triggers key AD-like effects: rab5 hyperactivation, enlarged early endosomes, loss of cholinergic neurons, reduced synaptic plasticity in memory-related brain regions, and memory deficits. These findings highlight APPL1's role in AD pathogenesis and its potential as a therapeutic target.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Presynaptic mu opioid receptors suppress the functional connectivity of ventral tegmental area dopaminergic neurons with aversion-related brain regions.","authors":"Yichen Wu, Tamara Perez-Rosello, Rajeshwar Awatramani, D James Surmeier","doi":"10.1523/JNEUROSCI.1194-24.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.1194-24.2025","url":null,"abstract":"<p><p>Opioid abuse poses a major healthcare challenge. To meet this challenge, the brain mechanisms underlying opioid abuse need to be more systematically characterized. It is commonly thought that the addictive potential of opioids stems from their ability to enhance the activity of ventral tegmental area (VTA) dopaminergic neurons. Indeed, activation of mu opioid receptors (MORs) dis-inhibits VTA dopaminergic neurons projecting to the nucleus accumbens, providing a substrate for the rewarding effects of opioids. However, the abuse potential of opioids has also been linked to their ability to suppress pain and aversive states. Although medial VTA dopaminergic neurons are commonly excited by aversive stimuli, the effects of MOR signaling on this circuitry have not been systematically explored. To fill this gap, a combination of anatomical, optogenetic, and electrophysiological approaches were used to study the afferent circuitry of paranigral VTA (pnVTA) dopaminergic neurons and its modulation by MOR signaling in male and female mice. These studies revealed that aversion-linked glutamatergic neurons in the lateral hypothalamus, ventrolateral periaqueductal gray, and lateral habenula innervated a subset of pnVTA dopaminergic neurons and that activation of presynaptic MORs suppressed their ability to drive pnVTA spiking. A distinct set of pnVTA dopaminergic neurons were innervated by lateral hypothalamus GABAergic neurons, which also were subject to MOR modulation. Thus, MORs robustly inhibit the ability of brain circuits coding aversive states to drive the activity of pnVTA dopaminergic neurons, suggesting that the addictive potential of opioids may stem in part from their ability to act as negative reinforcers.<b>Significance Statement</b> Opioid abuse is a severe, worldwide problem. The ventral tegmental area (VTA) is part of the brain circuitry underlying opioid dependence. Previous work has shown that opioid activation of mu opioid receptors (MORs) suppresses GABAergic inhibition of VTA dopaminergic neurons, enhancing dopamine release and reward. However, the central mechanisms responsible for the ability of opioids to alleviate pain are less clear. Here we demonstrate that MORs suppress the ability of neurons in three aversion-related brain regions to drive spiking in dopaminergic neurons located in the paranigral region of the VTA - a sub-region linked to pain perception. Thus, these studies add a new dimension to our understanding of the central actions of opioids and their potential role in opioid abuse.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Change of spiny neuron structure in the basal ganglia song circuit and its regulation by miR-9 during song development.","authors":"Hannah Jarrell, Ansab Akhtar, Max Horowitz, Zhi Huang, Zhimin Shi, ZhiDe Fang, XiaoChing Li","doi":"10.1523/JNEUROSCI.2276-23.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.2276-23.2025","url":null,"abstract":"<p><p>Juvenile zebra finches learn to sing by imitating conspecific songs of adults during a sensitive period early in life. Area X is a basal ganglia nucleus of the song control circuit specialized for song-related sensory-motor learning during song development. The structural plasticity and the molecular mechanisms regulating neuronal structure in Area X during song development and maturation are unclear. In this study, we examined the structure of spiny neurons, the main neuron type in Area X, at key stages of song development in male zebra finches. We report that dendritic arbor of spiny neurons expands during the sensitive period for song learning, and this initial growth is followed by pruning of dendrites and spines accompanied by changes in spine morphology as the song circuit matures. Previously, we showed that overexpression of miR-9 in Area X impairs song learning and performance and alters the expression of many genes that have important roles in neuronal structure and function (Shi et al., 2018). As an extension of that study, we report here that overexpression of miR-9 in spiny neurons in juvenile zebra finches reduces dendritic arbor complexity and spine density in a developmental stage-specific manner. We also show that miR-9 regulates structural maintenance of spiny neurons in adulthood. Together, these findings reveal dynamic microstructural changes in the song circuit during the sensitive period of song development and provide evidence that miR-9 regulates neuronal structure during song development and maintenance.<b>Significance Statement</b> Song development in juvenile zebra finches provides a model to study sensitive period plasticity for language development and related neural developmental disorders in humans. Area X is a basal ganglia nucleus essential for song-related sensory-motor learning in the zebra finch. We show that dendritic arbor of spiny neurons in Area X undergoes an initial growth and expansion followed by pruning of dendrites and spines during song development, and that this process is regulated by miR-9 in a developmental stage specific manner. These findings reveal the temporal profiles of structural development of key neurons in the basal ganglia song circuit and reveal a possible molecular mechanism for restricting sensitive period plasticity during vocal development.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"V2b neurons act via multiple targets to produce in phase inhibition during locomotion.","authors":"Mohini Sengupta, Alaina Bertram, Shuyu Iris Zhu, Geoff Goodhill, Martha W Bagnall","doi":"10.1523/JNEUROSCI.1530-24.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.1530-24.2025","url":null,"abstract":"<p><p>Spinal interneurons shape motor neuron activity. Gata3⁺ V2b neurons are a major inhibitory spinal population. These neurons are present at multiple spinal levels in mice, suggesting an important function in motor control. In zebrafish, our previous work showed that V2b neurons are evenly distributed along the spinal cord, where they act to slow down locomotion. However, the timing of V2b activity during locomotion, their postsynaptic targets other than motor neurons, and their recruitment across different behaviors remain unknown. In this study, we address these questions using larval zebrafish. First, via optogenetic mapping of output in the rostrocaudal axis, we demonstrate that V2b neurons robustly inhibit motor neurons and other major spinal populations, including V2a, V1, commissural neurons and other V2b neurons. V2b inhibition is patterned along the rostrocaudal axis, providing long-range inhibition to motor and V2a neurons but more localized inhibition of V1 neurons. Next, by recording V2b activity during different visually and electrically evoked movements, we show that V2b neurons are specifically recruited for forward swims and turns, but not for fast escape movements. Furthermore, a subset of V2b neurons also exhibited short-latency sensory-evoked activity preceding motor initiation. Finally, we show that V2b inhibition occurs in phase with the leading edge of the motor burst, in contrast to V1 inhibition which occurs in phase with the falling edge of the motor burst. Taken together, these data show that in axial motor networks, V2b neurons act via multiple targets to produce in phase, leading inhibition during locomotion.<b>Significance statement</b> Spinal interneurons are critical for executing and regulating movements. However, it has been challenging to understand their functions and interconnections because the spinal cord circuit is complex, with many long-range connections that are challenging to map. Using optogenetics in the larval zebrafish, we mapped the connectivity and activity of an inhibitory spinal population: V2b neurons. We show that V2b neurons not only inhibit motor neurons but also other major excitatory and inhibitory populations. With electrophysiology and calcium imaging, we recorded V2b activity during different behaviors and found that V2b neurons inhibit their targets on the rising phase of motor bursts, preferentially during slow locomotion. These results suggest that V2b neurons have a distinctive role in motor control.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144286984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Neurobiology of Cognitive Fatigue and Its Influence on Effort-Based Choice.","authors":"Grace Steward, Vivian Looi, Vikram S Chib","doi":"10.1523/JNEUROSCI.1612-24.2025","DOIUrl":"10.1523/JNEUROSCI.1612-24.2025","url":null,"abstract":"<p><p>Feelings of cognitive fatigue emerge through repeated mental exertion and are ubiquitous in our daily lives. However, there is a limited understanding of the neurobiological mechanisms underlying the influence of cognitive fatigue on decisions to exert. We use functional magnetic resonance imaging while participants (18 females, 10 males) chose to exert effort for reward, before and after bouts of fatiguing cognitive exertion. We found that when participants became cognitively fatigued, they were more likely to choose to forgo higher levels of reward for more effort. We describe a mechanism by which signals related to cognitive exertion in the dorsolateral prefrontal cortex influence effort value computations, instantiated by the insula, thereby influencing an individual's decisions to exert while fatigued. Our results suggest that cognitive fatigue plays a critical role in decisions to exert effort and provides a mechanistic link through which information about cognitive state shapes effort-based choice.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12160390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144062975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stereotyped Spatiotemporal Dynamics of Spontaneous Activity in Visual Cortex Prior to Eye Opening.","authors":"Luna Kettlewell, Audrey Sederberg, Gordon B Smith","doi":"10.1523/JNEUROSCI.1420-24.2025","DOIUrl":"10.1523/JNEUROSCI.1420-24.2025","url":null,"abstract":"<p><p>Over the course of development, functional sensory representations emerge in the visual cortex. Prior to eye opening, modular patterns of spontaneous activity form long-range networks that may serve as a precursor for mature network organization. Although the spatial structure of these networks has been well studied, their temporal features, which may contribute to their continued plasticity and development, remain largely uncharacterized. To address this, we imaged hours of spontaneous network activity in the visual cortex of developing ferrets of both sexes utilizing a fast calcium indicator (GCaMP8m) and wide-field imaging at high temporal resolution (50 Hz). The spatial structure of this activity was highly modular, exhibiting distributed and spatially segregated active domains and long-range correlated networks on the timescale of tens of milliseconds. We found that the majority of events showed a clear dynamic component in which the patterns of active modules shifted over the course of events lasting a few hundred milliseconds. Although only a minority of events were well fit with a linear traveling wave, more complex spatiotemporal patterns occurred in repeated and stereotyped motifs across hours of imaging. Finally, we found that the most frequently occurring single-frame spatial activity patterns were predictive of future activity and separable spatiotemporal trajectories extending over many hundreds of milliseconds. Together, our results demonstrate that spontaneous activity in the early developing cortex exhibits a stereotyped spatiotemporal structure on fast timescales, suggesting a potential role in the maturation and refinement of future functional representations.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12160389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144041150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gestational Chlorpyrifos Exposure Imparts Lasting Alterations to the Rat Somatosensory Cortex.","authors":"Jeffrey A Koenig, Catherine Haga, Nathan Cramer, Asaf Keller","doi":"10.1523/JNEUROSCI.0363-25.2025","DOIUrl":"10.1523/JNEUROSCI.0363-25.2025","url":null,"abstract":"<p><p>Chlorpyrifos is an organophosphorus pesticide used extensively in agricultural and residential settings for nearly 60 years. Gestational, subacute exposure to chlorpyrifos is linked to increased prevalence of neurodevelopmental disorders. Animal studies have modeled these neurobehavioral detriments; however, the functional alterations in the brain induced by this exposure remain largely unknown. To address this, we used a rat model of gestational chlorpyrifos exposure to interrogate the alterations in the developing somatosensory (barrel) cortex. Rat dams were exposed to chlorpyrifos (5 mg/kg) or vehicle on gestational days 18-21 via subcutaneous injection, with no overt acute toxicity. Acetylcholinesterase was modestly inhibited but returned to baseline levels by postnatal day 12. We performed whole-cell patch-clamp recordings on postnatal days 12-20 in both male and female progeny of the treated dams. A spike timing-dependent plasticity protocol revealed changes to the normal development of use-dependent plasticity, including interference in long-term synaptic depression. Recording inhibitory synaptic activity revealed an increase in the frequency of spontaneous postsynaptic currents and in paired-pulse ratios, in conjunction with a significant decrease in miniature postsynaptic currents. These findings suggest a presynaptic mechanism of inhibited GABA release, with potential disinhibition of inhibitory neurons. Evaluation of barrel cortex development displayed disruptions to normal barrel field patterning, with increases in both the septal area and total barrel field. We provide evidence for functional and structural alterations during brain development induced by in utero exposure to the organophosphorus pesticide chlorpyrifos that may account for the well-established behavioral outcomes.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12160401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144056838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}