Journal of Neuroscience最新文献

{"title":"Incorporation of a Cost of Deliberation Time in Perceptual Decision Making.","authors":"Shinichiro Kira, Ariel Zylberberg, Michael N Shadlen","doi":"10.1523/JNEUROSCI.2426-24.2025","DOIUrl":"10.1523/JNEUROSCI.2426-24.2025","url":null,"abstract":"<p><p>Many decisions benefit from the accumulation of evidence obtained sequentially over time. In such circumstances, the decision-maker must balance speed against accuracy, while considering the cost associated with the passage of time. A neural mechanism to achieve this balance is to accumulate evidence and to terminate the deliberation when enough evidence has accrued. To accommodate time costs, it has been hypothesized that the criterion to terminate a decision may become lax as a function of time. Here we tested this hypothesis by manipulating the cost of time in a perceptual choice-reaction time (RT) task. Human participants (both sexes) discriminated the direction of motion in a dynamic random-dot display, which varied in difficulty across trials. Unbeknownst to the participants, halfway through the experiment, we increased the time pressure by canceling a small fraction of trials, mimicking a broken fixation, if they had not made a decision by a provisional deadline. This subtle manipulation led participants to make faster but less accurate decisions. Choice and RT were well explained by a bounded evidence-accumulation process. We developed a novel computational method to estimate the time-dependent changes in the stopping bounds directly from the participants' RT and choice data. Our analysis revealed that the bounds decline as a function of time, and that this decline is steeper following the time-cost manipulation. The time-varying decision bounds approximate an optimal stopping policy, although the specific bound shape is idiosyncratic across individuals.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12311769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144585511","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":"Unveiling Cortical Criticality Changes along the Prodromal to the Overt Continuum of Alpha-Synucleinopathy.","authors":"Monica Roascio, Sheng H Wang, Vladislav Myrov, Felix Siebenhühner, Rosella Trò, Pietro Mattioli, Francesco Famà, Silvia D Morbelli, Matteo Pardini, Beatrice Orso, J Matias Palva, Dario Arnaldi, Gabriele Arnulfo","doi":"10.1523/JNEUROSCI.1871-24.2025","DOIUrl":"10.1523/JNEUROSCI.1871-24.2025","url":null,"abstract":"<p><p>Patients with idiopathic/isolated REM sleep behavior disorder (iRBD) are in the prodromal stage of alpha-synucleinopathies. Neurodegeneration early affects subcortical structures, including the substantia nigra, in iRBD patients. However, it remains unclear whether there is also an early neurodegeneration process affecting the cerebral cortex. We investigated whether EEG-derived metrics for aberrant cortical dynamics and imbalanced excitation-inhibition (E/I) correlate with disease severity in iRBD patients, aiming to better understand the pathophysiology progression from the prodromal to the overt stage of alpha-synucleinopathies. We retrospectively analyzed resting-state EEG recordings, as a marker of cortical function, and presynaptic dopaminergic imaging, a marker of subcortical function from 59 iRBD patients (9 female) who underwent longitudinal clinical evaluation alongside 46 age-matched healthy controls (22 female). We assessed power-law scaling in long-range temporal correlations (LRTCs), neuronal bistability, and functional E/I balance from the resting-state sensor EEG data and then correlated these to large-scale synchrony, nigrostriatal dopaminergic function, and clinical data. Compared with the control group, patients showed higher LRTCs and bistability in 2-7 Hz oscillations. Patients who developed parkinsonism/dementia exhibited hyperexcitability in 5-7 Hz compared with those who did not. This was also correlated with stronger phase synchrony. Both hyperexcitability in 5-7 Hz and bistability in 2-4 Hz negatively associated with nigrostriatal dopaminergic impairment. The iRBD patients, especially those closer to phenoconversion to parkinsonism or dementia, show clear aberrant cortical dynamics and hyperexcitability alongside substantia nigra impairment, suggesting that neurodegeneration in the prodromal stages affects both subcortical structures and cortical dynamics.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12311758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144561796","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":"Basal Forebrain to Ventral Tegmental Area Glutamatergic Pathway Promotes Emergence from Isoflurane Anesthesia in Mice.","authors":"Xia-Ting Gong, Zhang-Shu Li, Zhuo-Li Chen, Xin-Cheng Wu, Ling-Yi Shangguan, Zhi-Peng Xu, Li Chen, Changxi Yu, Ping Cai","doi":"10.1523/JNEUROSCI.0007-25.2025","DOIUrl":"10.1523/JNEUROSCI.0007-25.2025","url":null,"abstract":"<p><p>Recent evidence highlights the importance of glutamatergic neurons in the basal forebrain (BF) in promoting cortical activity; however, whether BF glutamatergic neurons are involved in regulating general anesthesia and the underlying neural circuits remains unclear. Here, we showed that the activity of BF glutamatergic neurons decreased during the induction of isoflurane anesthesia and restored during the emergence in mice. Optogenetic activation of these neurons significantly enhanced cortical activation, accelerated behavioral emergence, and improved physiological indicators in both male and female mice under isoflurane anesthesia. Specifically, activation of BF glutamatergic neurons shortened emergence time from isoflurane anesthesia, decreased isoflurane sensitivity, and increased arousal scores of mice. Moreover, optogenetic activation of BF glutamatergic neurons decreased EEG delta power and burst suppression ratio, while increasing pupil size and respiration rate in mice during isoflurane anesthesia. Similar results were observed during the optogenetic activation of BF glutamatergic terminals in the ventral tegmental area (VTA). Additionally, we found that the activity of BF glutamatergic neurons and VTA glutamatergic neurons synchronously fluctuated during isoflurane anesthesia, and optogenetic activation of BF glutamatergic terminals in the VTA potently increased the calcium signals in VTA glutamatergic neurons during isoflurane anesthesia. Collectively, these findings demonstrate that BF glutamatergic neurons promote emergence from isoflurane anesthesia by activating VTA glutamatergic neurons.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12311767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144509204","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":"Projection of Cortical Beta Band Oscillations to a Motor Neuron Pool across the Full Range of Recruitment.","authors":"Emanuele Abbagnano, Alejandro Pascual-Valdunciel, Blanka Zicher, Jaime Ibañez, Dario Farina","doi":"10.1523/JNEUROSCI.0453-25.2025","DOIUrl":"10.1523/JNEUROSCI.0453-25.2025","url":null,"abstract":"<p><p>Cortical beta band oscillations (13-30 Hz) are associated with sensorimotor control, but their precise role remains unclear. Evidence suggests that for low-threshold motor neurons (MNs), these oscillations are conveyed to muscles via the fastest corticospinal fibers. However, their transmission to MNs of different sizes may vary due to differences in the relative strength of corticospinal and reticulospinal projections across the MN pool. Consequently, it remains uncertain whether corticospinal beta transmission follows similar pathways and maintains consistent strength across the entire MN pool. To investigate this, we examined beta activity in MNs innervating the tibialis anterior muscle across the full range of recruitment thresholds in a study involving 12 participants of both sexes. We characterized beta activity at both the cortical and motor unit (MU) levels, while participants performed contractions from mild to submaximal levels. Corticomuscular coherence remained unchanged across contraction forces after normalizing for the net MU spike rate, suggesting that beta oscillations are transmitted with similar strength to MNs, regardless of size. To further explore beta transmission, we estimated corticospinal delays using the cumulant density function, identifying peak correlations between cortical and muscular activity. Once compensated for variable peripheral axonal propagation delay across MNs, the corticospinal delay remained stable, and its value (∼14 ms) indicated projections through the fastest corticospinal fibers for all MNs. These findings demonstrate that corticospinal beta band transmission is determined by the fastest pathway connecting in the corticospinal tract, projecting similarly across the entire MN pool.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12311756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144602147","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":"Stress Sensitization of Neurons in the Dentate Gyrus Is Dependent on Neuronal Interleukin-1 Receptor Signaling and Is Associated with Increased Synaptic Plasticity, Perineuronal Nets, and Excitatory/Inhibitory Input Imbalance.","authors":"Ethan J Goodman, Riley M Britt, Fangli Zhao, Amara C Davis, Lynde M Wangler, Ethan Emami, Samuel P Swanson, Candice C Askwith, John F Sheridan, Jonathan P Godbout","doi":"10.1523/JNEUROSCI.2209-24.2025","DOIUrl":"10.1523/JNEUROSCI.2209-24.2025","url":null,"abstract":"<p><p>Repeated social defeat (RSD) in mice causes sensitization of hippocampal neurons associated with enhanced contextual fear memory. Because enhanced fear memory is an integral component of posttraumatic stress disorder, the physiological basis of neuronal sensitization in the hippocampus after social defeat was investigated in male mice using two interventions: microglia depletion (CSF1R antagonist, PLX5622) and neuronal (Vglut2⁺) IL-1R1^-/- mice. Here, two single-nuclei (sn) RNAseq data sets using these interventions were integrated and compared. Social defeat altered the transcriptional profiles of CA1 (Satb2⁺), dentate gyrus (DG, Prox1⁺), and inhibitory (Pval⁺) neurons, and these stress profiles were influenced by nIL-1R1, microglia, or both. In DG neurons, differentially expressed genes and canonical pathways related to cAMP response element (CREB), calcium/calmodulin kinases, bassoon, and glutamatergic signaling were robustly increased by RSD, and these were selectively dependent on nIL-1R1. Based on the snRNAseq data, neuronal stability and plasticity within the hippocampus were assessed. For instance, social defeat increased perineuronal nets around inhibitory (Pval⁺) neurons in the DG, and these were influenced by both nIL-1R1 and microglia. In addition, RNAscope confirmed that bassoon RNA was amplified after social defeat in the CA1 and DG, and these increases were selectively dependent on nIL-1R1. Last, electrophysiological analyses showed that both spontaneous excitatory and inhibitory postsynaptic current amplitudes in the DG were influenced by social defeat in a nIL-1R1-dependent manner. Collectively, sensitization of dentate gyrus neurons after social defeat requires neuronal IL-1R1 and is associated with enhanced CREB-bassoon signaling and disruption of the excitatory/inhibitory input balance.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12311764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144561795","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":"Online Movements Reflect Ongoing Deliberation.","authors":"Jan A Calalo, Truc T Ngo, Seth R Sullivan, Kathryn Strand, John H Buggeln, Rakshith Lokesh, Adam M Roth, Michael J Carter, Isaac L Kurtzer, Joshua G A Cashaback","doi":"10.1523/JNEUROSCI.1913-24.2025","DOIUrl":"10.1523/JNEUROSCI.1913-24.2025","url":null,"abstract":"<p><p>From navigating a crowded hallway to skiing down a treacherous hill, humans are constantly making decisions while moving. Insightful past work has provided a glimpse of decision deliberation at the moment of movement onset. Yet it is unknown whether ongoing deliberation can be expressed during movement, following movement onset and prior to any decision. Here we tested the idea that an ongoing deliberation continually influences motor processes-prior to a decision-directing online movements. The deliberation process was manipulated by having humans of either sex observe tokens that moved into a left or right target. Supporting our hypothesis, we found that lateral hand movements reflected deliberation, prior to a decision. We also found that a deliberation urgency signal, which more heavily weighs later evidence, was fundamental to predicting decisions and explains past movement behavior in a new light. Our paradigm promotes the expression of ongoing deliberation through movement, providing a powerful new window to understand the interplay between decision and action.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12311772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144545864","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":"The orbitofrontal cortex underlies consolidation of Pavlovian anticipatory arousal responses in macaque monkeys.","authors":"Jaewon Hwang,Pamela L Noble,Mary K L Baldwin,Elisabeth A Murray","doi":"10.1523/jneurosci.0619-25.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.0619-25.2025","url":null,"abstract":"Altered arousal is characteristic of many mental health disorders, including major depressive disorder (MDD). Several studies link neural activity in orbitofrontal cortex (OFC) with anticipation of reward, including anticipatory sympathetic arousal, which is blunted in MDD. We therefore studied acquisition and consolidation of appetitive Pavlovian memories in two groups of adult male rhesus monkeys: unoperated controls (N = 4) and those with selective neurotoxic lesions of OFC (N = 4). The dependent measure was conditioned sympathetic arousal as indexed by differential pupil dilation, and the key comparison was dilation in response to a visual cue that predicted the delivery of a large fluid reward (CS+) vs. a cue that predicted no reward (CS-). Control procedures ruled out global effects of the lesion on pupil dilation. All four unoperated controls and all four monkeys with OFC lesions acquired a conditioned increase in pupil size in response to the CS+. However, three of the four monkeys in the lesion group failed to consolidate the memory underlying this response. In contrast to this impairment, monkeys with OFC lesions acquired and consolidated an operant visual discrimination for the same reward and did so at the same rate as controls. These findings point to a specialized role for OFC in consolidating memories underlying positive affective responses, which further implicates OFC dysfunction in the blunted positive affect characteristic of MDD and suggests therapeutic approaches involving enhanced consolidation and/or reconsolidation of associative memories.Significance statement Blunted anticipation of positive events is characteristic of many mental health disorders, including major depressive disorder (MDD). Cortical circuits underlying anticipatory responses have been identified in rodent models, but it is likely that different mechanisms operate in anthropoid primates, the clade that includes humans and monkeys. Anthropoids have cortical areas that rats and mice lack, and here we show that-in a macaque monkey model-some of these areas are necessary for consolidating memories that produce autonomic arousal in anticipation of rewards. Specifically, the integrity of granular orbitofrontal cortex (OFC)-the part of OFC specific to primates-is essential for macaque monkeys to consistently generate arousal in response to visual cues that predict positive events.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"59 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144720304","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":"Ciliary ARL13B is Essential for Vision and Morphogenesis of Cone Outer Segments.","authors":"Alexis Crockett,Sierra Kuzak,Thamaraiselvi Saravanan,Tongju Guan,Tamara Caspary,Hunter Aliff,George Holmes,Faezeh Moakedi,Visvanathan Ramamurthy","doi":"10.1523/jneurosci.0752-25.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.0752-25.2025","url":null,"abstract":"Mutations in ARL13B lead to Joubert syndrome, a ciliopathy with neurological and retinal abnormalities. In photoreceptors, ARL13B localizes to the connecting cilia and outer segments. However, the specific function and the need for ARL13B in photoreceptor cilia remain unclear. We used a knock-in mouse model with the Arl13b V358A mutation, which disrupts ciliary localization while preserving guanine exchange factor (GEF) activity, to investigate the role of ARL13B in the photoreceptor cilia. Using female and male littermates, we show by electroretinogram (ERG) that the exclusion of ARL13B from photoreceptor cilia leads to an early loss of cone-mediated vision followed by a decline in rod-mediated vision. This phenotype was unique to the cilia-excluded V358A model, as analysis using the GEF impaired R79Q model did not show similar changes in photoreceptor function. Morphological analyses using immunohistochemistry (IHC) and Transmission Electron Microscopy (TEM) revealed shortened cone axonemes and structural abnormalities in cone outer segments. IHC staining further demonstrated that loss of ciliary ARL13B disrupts the localization of intraflagellar transport protein 88 (IFT88) in photoreceptors. In addition, the phosphoinositol-4,5-bisphosphate (PIP2) binding protein, Tubby-like protein 1 (TULP1), associated with inherited retinal diseases, was mislocalized to cone outer segments in the V358A model. These findings establish an essential role for ciliaryARL13B in maintaining cone photoreceptor axoneme length, outer segment organization, and proper protein localization. They also suggest that phosphoinositide gradients are critical for cone photoreceptor function and morphology. Together, our findings provide new insights into the molecular mechanisms regulating photoreceptor cilia and the pathogenesis of ciliopathies.Significance Statement Mutations in ARL13B cause blindness in humans. In a mouse model lacking ARL13B, photoreceptor neurons rapidly degenerate, leading to visual impairment. Despite its critical role in vision, the specific function of ARL13B within photoreceptor cilia remains unclear. Using a mouse model in which ARL13B is excluded from cilia but retains enzymatic activity, we demonstrate that ARL13B is essential for early cone photoreceptor function while rod photoreceptor function declines progressively. The absence of ciliary ARL13B results in shortened axonemes, structural abnormalities, loss of cone photoreceptors, and mislocalization of key ciliary proteins. Our findings establish ARL13B as a crucial regulator of cone photoreceptor architecture and protein distribution.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"721 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144720263","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":"Phase consistency dynamics of memory encoding.","authors":"Ryan A Colyer, Michael J Kahana","doi":"10.1523/JNEUROSCI.2077-24.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.2077-24.2025","url":null,"abstract":"<p><p>Human and animal studies implicate theta and alpha oscillations in memory function. We tested whether theta, alpha, and beta phase consistency predicts memory encoding dynamics in neurosurgical patients performing delayed free recall tasks with either unrelated (N=188: 99 male, 89 female) or categorized words (N=157: 88 male, 69 female). We observed widespread post-stimulus phase consistency (3-21 Hz) and, crucially, identified distinct frequency-specific patterns predictive of successful encoding. Specifically, increased early-list item recall was significantly correlated across subjects with increased theta (3-7 Hz) phase consistency. Subsequent recall analyses, controlling for serial position, revealed distinct frequency signatures for successfully encoded items: theta (3-6 Hz) and alpha (9-14 Hz) for unrelated lists, and theta (3-6 Hz) and beta (14-19 Hz) for categorized lists. Regional analyses for unrelated lists highlighted the lateral temporal cortex for theta effects and the prefrontal cortex for both theta and alpha consistency. These findings provide novel evidence for the frequency-specific presence of increased phase consistency during episodic encoding, revealing its sensitivity to both item context and temporal position within a learning sequence.<b>Significance statement</b> Neural oscillations are implicated in memory encoding, but their precise roles are still being defined. Our study leverages large-scale intracranial EEG from participants undergoing word recall experiments, and introduces analytical innovations for robustly quantifying phase consistency with differing numbers of recalled versus forgotten items. This methodology reveals that phase consistency across different frequency bands (theta, alpha, beta) predicts memory formation. We demonstrate a role for theta consistency in encoding early list items and show that the brain recruits different oscillatory patterns (alpha or beta alongside theta) depending on item context (unrelated vs. categorized lists). These findings advance our understanding of the frequency-specific neural mechanisms supporting human episodic memory, revealing how the brain adapts its encoding strategies based on informational structure.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144734993","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":"F-BAR proteins CIP4 and FBP17 function in cortical neuron radial migration and process outgrowth.","authors":"Lauren A English, Russell J Taylor, Jillian Palmos, Connor J Cameron, Emily A Broker, Emma M TeVogt, Erik W Dent","doi":"10.1523/JNEUROSCI.1952-24.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.1952-24.2025","url":null,"abstract":"<p><p>Neurite initiation from newly born neurons is a critical step in neuronal differentiation and migration. Neuronal migration in the developing cortex is accompanied by dynamic extension and retraction of neurites as neurons progress through bipolar and multipolar states. However, there is a relative lack of understanding regarding how the dynamic extension and retraction of neurites is regulated during neuronal migration. In recent work we have shown that CIP4, a member of the F-BAR family of membrane bending proteins, inhibits cortical neurite formation in culture, while family member FBP17 induces premature neurite outgrowth. These results beg the question of how CIP4 and FBP17 function in radial neuron migration and differentiation in vivo, including the timing and manner of neurite extension and retraction. Indeed, the regulation of neurite outgrowth is essential for the transitions between bipolar and multipolar states during radial migration. To examine the effects of modulating expression of CIP4 and FBP17 in vivo, we used <i>in utero</i> electroporation, in combination with our published Double UP technique, to compare knockdown or overexpression cells with control cells within the same mouse tissue of either sex. We show that either knockdown or overexpression of CIP4 and FBP17 results in the marked disruption of radial neuron migration by modulating neuronal morphology and neurite outgrowth, consistent with our findings in culture. Our results demonstrate that the F-BAR proteins CIP4 and FBP17 are essential for proper radial migration in the developing cortex and thus play a key role in cortical development.<b>Significance statement</b> During embryonic development, radial migration of newly born cortical neurons is a complex process that underlies the proper formation of the neocortex, the outermost layers of neurons in the brain. Disruptions in radial migration results in profound effects on cognitive function and can lead to devastating developmental disabilities. To better understand this critical process in brain development, we examined two members of the F-BAR family of membrane-bending proteins, CIP4 and FBP17, which are present in the developing brain. We demonstrate that intracellular concentrations of these proteins must be tightly regulated. Increasing or decreasing protein levels has profound effects on neuronal morphology and proper radial migration, suggesting they are key players in cortical development.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144734992","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}