Journal of Neuroscience最新文献

{"title":"Amygdala regulates social motivation for selective vocal imitation in zebra finches.","authors":"Tomoko G Fujii,Masashi Tanaka","doi":"10.1523/jneurosci.2435-24.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.2435-24.2025","url":null,"abstract":"Imitation plays a key role in the acquisition of speech and cultural behaviors. Studies suggest that social interaction facilitates imitative learning, indicating that neural circuits involved in social behaviors can also influence the process of imitation. Vocal imitation in juvenile songbirds serves as a valuable model to investigate this idea. Here, we explore the mechanisms of tutor-pupil social interaction and selective song learning in male zebra finches, with a particular focus on the amygdala, which can regulate social behaviors via its processing of values and emotions in mammals. When sequentially exposed to two tutors, normal pupils selectively learned song from the tutor who sang longer but less frequently. When hearing songs, pupils preferentially approached the selected tutor. Excitotoxic lesions of the amygdala increased pupils' social motivation toward tutors yet diminished their song-responsive approach, especially to the selected tutor. Whereas the pupils with amygdala lesions retained their ability to imitate song, the tutor selection became more unpredictable with diminished preference for a specific tutor. Neuronal tracing confirmed that the zebra finch amygdala is connected to the circuits involved in social functions but lacks direct connections to those critical for song control and learning. These results suggest that the amygdala regulates social motivation and tutor selection in juvenile zebra finches, highlighting its role in imitative learning.Significance Statement Social interaction plays a critical role in imitation, particularly in the acquisition of speech and cultural behaviors like dance and song. Although studies in rodents indicate the involvement of the amygdala in social behaviors and social learning, the mechanisms coordinating social behaviors and imitative learning remain poorly understood. Vocal imitation in juvenile songbirds is an ideal model to investigate such mechanisms. Here, we report that lesioning the amygdala in juvenile zebra finches increases overall social motivation but disrupts selective song learning and their preferential approach to the selected tutor. These findings provide new insights into the social function of the amygdala in imitation.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"33 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144146045","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":"Brain-behavior differences in pre-modern and modern lineages of domestic dogs.","authors":"Sophie A Barton,Jeroen B Smaers,James A Serpell,Erin E Hecht","doi":"10.1523/jneurosci.2032-24.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.2032-24.2025","url":null,"abstract":"Although domestic dogs were the first domesticated species, the nature of dog domestication remains a topic of ongoing debate. In particular, brain and behavior changes associated with different stages of the domestication process have been difficult to disambiguate. Most modern Western breed dogs possess highly derived physical and behavioral traits because of intense artificial selection for appearance and function within the past 200 years. In contrast, pre-modern dogs, including primitive/ancient breeds, village dogs, and New Guinea Singing Dogs, have undergone less intensive artificial selection and retain more ancestral characteristics. Consequently, comparisons between modern and pre-modern dogs can shed light on brain and behavior changes that have occurred recently in the domestication process. Here, we addressed this question using a voxel-based morphometry analysis of structural MRI images from 72 modern breed dogs and 13 pre-modern dogs (32 females). Modern breed dogs show widespread expansions of neocortex and reductions in the amygdala and other subcortical regions. Furthermore, cortical measurements significantly predicted individual variation in trainability, while amygdala measurements significantly predicted fear scores. These results contrast with the longstanding view that domestication consistently involves reduction in brain size and cognitive capacity. Rather, our results suggest that recent artificial selection has targeted higher-order brain regions in modern breed dogs, perhaps to facilitate behavioral flexibility and close interaction and cooperation with humans.Significance Statement This study provides novel insights into the neural changes associated with artificial selection during dog domestication by comparing brain morphology between modern breed dogs and a unique and rare sample of pre-modern dogs, including ancient breeds, village dogs, and New Guinea singing dogs. Our findings demonstrate that modern breed dogs exhibit significant cortical expansion linked to trainability and pre-modern dogs show amygdala enlargement associated with heightened fear, suggesting that brain evolution has happened rapidly in a species embedded in the anthropogenic environment.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"37 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144122110","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":"Inhibition of Rho-associated kinases ROCK1 and ROCK2 as a Therapeutic Strategy to Reactivate the Repressed FXN Gene in Friedreich Ataxia.","authors":"Minggang Fang,Shahid Banday,Sara K Deibler,Tessa M Simone,Madison Coleman,Emerald O'Connor,Rui Li,Lihua Julie Zhu,Michael R Green","doi":"10.1523/jneurosci.2307-24.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.2307-24.2025","url":null,"abstract":"Friedreich ataxia (FA) is an autosomal recessive disease characterized by progressive damage to the nervous system and severe cardiac abnormalities. The disease is caused by a GAA•TTC triplet repeat expansion in the first intron of the FXN gene, which results in epigenetic repression of FXN transcription and reduction in FXN (frataxin) protein which results in mitochondrial dysfunction. Factors and pathways that promote FXN repression represent potential therapeutic targets whose inhibition would restore FXN transcription and frataxin protein levels. Here, we performed a candidate-based RNAi screen to identify kinases, a highly druggable class of proteins, that when knocked down upregulate FXN expression. Using this approach, we identified Rho kinase ROCK1 as a critical factor required for FXN repression. ShRNA-mediated knockdown of ROCK1, or the related kinase ROCK2, increases FXN mRNA and frataxin protein levels in FA patient-derived induced pluripotent stem cells (iPSCs) and differentiated neurons and cardiomyocytes to levels observed in normal cells. We demonstrate that small molecule ROCK inhibitors, including the FDA-approved drug belumosudil and fasudil, reactivate FXN expression in cultured FA iPSCs, neurons, cardiomyocytes, and FA patient primary fibroblasts, and ameliorate the characteristic mitochondrial defects in these cell types. Remarkably, treatment of transgenic FA mice of both sexes with belumosudil or fasudil upregulates FXN expression, ameliorates the mitochondrial defects in the brain and heart tissues, and improves motor coordination and muscle strength. Collectively, our study identifies ROCK kinases as critical repressors of FXN expression and provides preclinical evidence that FDA approved ROCK inhibitors may be repurposed for treatment of FA.Significance Statement Friedreich ataxia is a debilitating disorder caused by epigenetic repression of the frataxin (FXN) gene, leading to neurodegeneration and cardiomyopathy. Through an RNA interference screen, we identified ROCK1 and ROCK2 kinases as critical repressors of FXN expression, making them promising therapeutic targets for upregulating FXN in patient-derived cells. Treatment with small-molecule ROCK inhibitors, including the FDA-approved drug belumosudil and clinically advanced fasudil, restores frataxin levels, alleviates mitochondrial defects, and improves disease phenotypes in cells and animal models. These findings establish ROCK kinases as targets for Friedreich ataxia therapy and open new avenues for repurposing existing ROCK inhibitors, warranting clinical exploration.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"33 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144122111","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":"Functional Roles of Gastrin-Releasing Peptide-Producing Neurons in the Suprachiasmatic Nucleus: Insights into Photic Entrainment and Circadian Regulation.","authors":"Ruoshi Li,Ran Inoue,Hisashi Mori,Arisa Hirano,Takeshi Sakurai","doi":"10.1523/jneurosci.0065-25.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.0065-25.2025","url":null,"abstract":"The suprachiasmatic nucleus (SCN) serves as the central circadian clock in mammals, coordinating daily rhythms in both behavior and physiology. In the SCN, gastrin-releasing peptide (GRP)-producing neurons (GRPNs) are predominantly located in the core region, suggesting their possible involvement in photic entrainment. However, the specific contribution of GRPNs to the regulation of circadian rhythms remains poorly understood. This study utilized a Cre-driver mouse line, Grp-iCre knock-in (KI) mice, in which Cre recombinase is exclusively expressed in GRPNs, allowing the selective manipulation of SCN GRPNs to investigate their characteristics and functional roles in circadian regulation. All experiments were conducted in adult male mice. Anatomical tracing revealed that SCN GRPNs primarily project to the thalamus and hypothalamus, whereas input mapping demonstrated that SCN GRPNs receive most synaptic inputs from within the SCN. Behavioral analyses revealed that neither GRP deficiency nor ablation of SCN GRPNs significantly affected circadian locomotor activity rhythms or photic entrainment. However, chemogenetic stimulation of the SCN GRPNs is sufficient to induce phase shifts in behavioral rhythms. Additionally, calcium imaging with fiber photometry indicated that SCN GRPNs quickly responded to photic stimulation, with increased neural activity following retinal exposure to white light. These findings suggest that SCN GRPNs play a role in photic entrainment, albeit potentially redundant with other neuronal populations such as vasoactive intestinal peptide-producing neurons.Significance Statement The suprachiasmatic nucleus (SCN) functions as the central circadian clock in mammals, synchronizing internal rhythms with the external light-dark cycle. Among its diverse cell types, gastrin-releasing peptide (GRP)-producing neurons (GRPNs) have been implicated in light-based entrainment, but their specific roles remained unclear. Using targeted genetic tools, we demonstrated that these neurons respond rapidly to retinal light stimulation and, when artificially activated, can induce phase shifts in behavioral rhythms. However, eliminating these neurons does not disrupt circadian behavior or molecular clock rhythms, indicating functional redundancy within the SCN network. Our findings clarify the modulatory-but non-essential-role of GRPNs in light-induced entrainment and underscore the complexity and resilience of circadian circuit organization.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"44 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144122113","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":"Neural signatures of flexible multiple timing.","authors":"Shahar Haim,Nir Ofir,Leon Y Deouell,Ayelet N Landau,Eran Lottem","doi":"10.1523/jneurosci.2041-24.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.2041-24.2025","url":null,"abstract":"The human ability to track overlapping and asynchronous time intervals is crucial for a myriad of tasks, from engaging in conversation to driving a car. Additionally, unexpected events can trigger rapid, on-the-fly adjustments, necessitating quick updating of both timing intervals and action planning. Such events require immediate recalibration of decision variables to allow the system to promptly adapt to new stimuli and update the timing mechanisms accordingly. In this study, we assessed human male and female participants' ability to track two simultaneous and asynchronous beep trains and determine which one ended first. Due to the stochastic nature of the beeps, participants frequently had to reorient their intended actions in order to identify which train was more likely to have ended. We found that they were able to do this accurately, demonstrating timing performance that was comparable to that of a single train. At the neural level, we recorded slowly evolving EEG potentials that encoded a single interval, the one associated with the currently intended action. Upon an intention switch, when participants had to reorient to a previously unintended action, the EEG response amplitude was reset to reflect the new intended interval. In contrast, when participants were instructed to disregard one of the beep trains, EEG responses solely reflected the intervals of the sequence they attended to. This flexibility in response highlights the brain's ability to dynamically reconfigure cognitive processes in real-time, ensuring that actions remain contextually appropriate despite sudden changes in the environment.Significance statement The human brain exhibits a remarkable ability to track temporal patterns and rapidly adjust timing and action plans in response to unexpected events. Using a novel task, we show that humans can flexibly process two independent, asynchronous sound trains and accurately determine which ends first. The unpredictable nature of the stimuli required frequent shifts in participants' intentions and adjustments in timing. EEG recordings reveal neural signals that mirror this adaptability, dynamically aligning with behavioral changes. These findings highlight the brain's capacity for real-time cognitive flexibility in response to sudden environmental changes, offering new insights into the mechanisms of complex timing behavior.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"97 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144122112","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":"Attention alters population spatial frequency tuning.","authors":"Luis D Ramirez,Feiyi Wang,Sam Ling","doi":"10.1523/jneurosci.0251-25.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.0251-25.2025","url":null,"abstract":"Spatial frequency (SF) selectivity serves as a fundamental building block within the visual system, determining what we can and cannot see. Attention is theorized to augment the visibility of items in our environment by changing how we process SFs. However, the specific neural mechanisms underlying this effect remain unclear, particularly in humans. Here, we used functional magnetic resonance imaging (fMRI) to measure voxel-wise population SF tuning (pSFT), which allowed us to examine how attention alters the SF response profiles of neural populations in early visual cortex (V1-V3). In the scanner, participants (5 female, 3 male) were cued to covertly attend to one of two spatially competing letter streams, each defined by low or high SF content. This task promoted feature-based attention directed to a particular SF, as well as the suppression of the irrelevant stream's SF. Concurrently, we measured pSFT in a task-irrelevant hemifield to examine how the known spatial spread of feature-based attention influenced the SF tuning properties of neurons sampled within a voxel. We discovered that attention elicited attractive shifts in SF preference, towards the attended SF. This suggests that attention can profoundly influence populations of SF preference across the visual field, depending on task goals and native neural preferences.Significance Statement The spatial frequency (SF) preference of neural populations in early visual cortex governs the coarse and fine details we can see. However, the brain is limited in what it can process, requiring selective attention to prioritize relevant over irrelevant details. Although SF is fundamental to visual processing, it remains unclear how selective attention to SF alters population-level responses to SF. Using fMRI, we measured SF preferences in V1-V3 while participants deployed feature-based attention to one of two competing stimuli solely defined by their SF. We found that attention produced attractive shifts in preferences across the visual field, towards the attended SF, demonstrating that voluntary attention can flexibly reshape SF preferences in early visual cortex.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"18 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144122152","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":"Microglia supports both the singular form of LTP expressed by the lateral perforant path and episodic memory.","authors":"J Chavez,A A Le,J Quintanilla,J C Lauterborn,Y Jia,A M Tagne,H L Lee,K M Jung,D Piomelli,G Lynch,C M Gall","doi":"10.1523/jneurosci.1322-24.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.1322-24.2025","url":null,"abstract":"We report here that microglia exert a surprisingly discrete but functionally critical influence on synaptic plasticity in mouse hippocampus. Treatment of adult male mice with colony stimulating factor 1 receptor antagonist PLX5622 (PLX), with resultant depletion of forebrain microglia, did not disturb basal synaptic transmission at four synaptic connections in hippocampus. Long-term potentiation (LTP) was also intact for three of these sites, but the singular, endocannabinoid-dependent form of LTP expressed by lateral perforant path (LPP) input to the dentate gyrus (DG) was severely impaired. The LPP-LTP defect occurred in conjunction with a pronounced increase in DG (but not neocortical) levels of 2-arachidonoylglycerol (2-AG), the retrograde (spine-to-terminal) endocannabinoid messenger that initiates LPP-LTP. Despite this, concentrations of the 2-AG synthetic enzyme diacylglycerol lipase were not affected by PLX treatment. Synaptic levels of the cannabinoid type 1 receptor, which mediates 2-AG effects on LPP-LTP, were similarly unaffected. Prior work has implicated the LPP in episodic memory. We determined that the LPP-LTP impairment in PLX-treated mice was accompanied by a failure to acquire the three basic elements of an episode: the identities, locations, and presentation order for a collection of olfactory cues. Treatment with JZL184, which inhibits the 2-AG degradative enzyme monoglyceride lipase, restored both LPP-LTP and episodic 'What' encoding in PLX-treated mice. We conclude that microglia selectively regulate endocannabinoid transmission at the LPP-DG synapse and thereby potently influence synaptic plasticity at the initial stage of a cortico-hippocampal circuit that is critical for episodic memory.Significance Statement There has been considerable interest in microglial involvement in the moment-to-moment operations of the brain. However, the present studies show that, with one prominent exception, treatments that significantly deplete forebrain microglia have no detectable influence on synaptic operations at multiple sites within hippocampus. Nevertheless, long-term potentiation was selectively disrupted within the lateral perforant path, a primary cortical input to hippocampus. Relatedly, microglial depletion was associated with severe impairments in encoding the principal components of episodic memory. These results indicate microglial influences on synaptic transmission are surprising discrete and yet essential for orderly cognition.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"57 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144122114","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":"Brain Topological Changes in Subjective Cognitive Decline and Associations with Amyloid Stages.","authors":"Xueyan Jiang,Mingkai Zhang,Chuyao Yan,Marcel Daamen,Henning Boecker,Feng Yue,Frank Jessen,Xiaochen Hu,Ying Han","doi":"10.1523/jneurosci.2310-24.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.2310-24.2025","url":null,"abstract":"This study examined how amyloid burden affects structural and functional brain network topology in subjective cognitive decline (SCD), a risk condition for Alzheimer's disease (AD). Functional and structural brain networks were analyzed in 100 individuals with SCD and 86 normal controls (both sexes included) using resting-state functional MRI and diffusion tensor imaging. Topological properties of brain networks were evaluated as indicators of information exchange efficiency and network robustness. Amyloid burden in 55 SCD participants was measured using amyloid PET imaging and a frequency-based staging method, which defined global and regional amyloid burden for four anatomical stages. Compared to normal controls, individuals with SCD exhibited increased functional nodal efficiency and structural nodal betweenness in the left anterior and median cingulate gyri, with no differences in network-level properties. Amyloid staging revealed four cortical divisions: stage 1, fusiform and lateral temporal gyri; stage 2, occipital areas; stage 3, default mode network (DMN), midline brain and lateral frontotemporal areas; and stage 4, the remaining cortex. The global and regional amyloid burden of each cortical stage were positively associated with the node-level properties of a set of DMN hubs, with the left anterior and posterior cingulate gyri being congruently associated with all amyloid stages. These findings suggest that amyloid burden continuously influences network adaptations through DMN hubs, irrespective of local proximity to pathology. Increased nodal properties in cortical hubs may reflect heightened information-processing demands during early amyloid deposition in this population at risk for AD.Significance Statement Amyloid spreads throughout the cortex in AD. It is unclear whether early amyloid deposition may trigger system-level network reorganization in SCD who are at risk for AD. We examined the brain topology alterations in SCD and its relationship with amyloid deposition at different cortical stages. We found increased node-level topological properties, in the core default mode network region (i.e., the cingulate cortex) in SCD. Increasing regional amyloid load at all stages showed consistent associations with the increasing node-level topological properties of the cingulate cortex in SCD. Our findings suggest that amyloid deposition impacts the system-level network adaptation via the cingulate cortex already at the very early stage and is unlikely to have a local effect in this AD risk population.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"57 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144122115","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":"Mef2c Controls Postnatal Callosal Axon Targeting by Regulating Sensitivity to Ephrin Repulsion.","authors":"Sriram Sudarsanam, Luis E Guzman-Clavel, Nyle Dar, Jakub Ziak, Naseer Shahid, Xinyu O Jin, Alex L Kolodkin","doi":"10.1523/JNEUROSCI.0201-25.2025","DOIUrl":"10.1523/JNEUROSCI.0201-25.2025","url":null,"abstract":"<p><p>Intracortical circuits, including long-range callosal projections, are crucial for information processing. The development of neuronal connectivity in the cerebral cortex is contingent on ordered emergence of neuronal classes followed by the formation of class-specific axon projections. However, the genetic determinants of intracortical axon targeting are still unclear. We find that the transcription factor myocyte enhancer factor 2-c (Mef2c) directs the development of somatosensory cortical (S1) Layer 4 and 5 identity in murine postmitotic pyramidal neurons during embryogenesis. During postnatal development, <i>Mef2c</i> expression shifts to Layer 2/3 callosal projection neurons (L2/3 CPNs). At this later developmental stage, we identify a novel function for <i>Mef2c</i> in contralateral homotopic domain targeting by S1-L2/3 CPN axons. We employ functional manipulation of EphrinA-EphA signaling in <i>Mef2c</i> mutant CPNs and demonstrate that Mef2c represses <i>EphA</i>6 to desensitize S1-L2/3 CPN axons to EphrinA5 repulsion at their contralateral targets. Our work uncovers dual roles for <i>Mef2c</i> in cortical development: regulation of laminar subtype specification during embryogenesis and axon targeting in postnatal callosal neurons.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12096051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144006285","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":"Neocortical and Hippocampal Theta Oscillations Track Audiovisual Integration and Replay of Speech Memories.","authors":"Emmanuel Biau, Danying Wang, Hyojin Park, Ole Jensen, Simon Hanslmayr","doi":"10.1523/JNEUROSCI.1797-24.2025","DOIUrl":"10.1523/JNEUROSCI.1797-24.2025","url":null,"abstract":"<p><p>\"Are you talkin' to me?!\" If you ever watched the masterpiece \"Taxi Driver\" directed by Martin Scorsese, you certainly recall the monologue during which Travis Bickle rehearses an imaginary confrontation in front of a mirror. While remembering this scene, you recollect a myriad of speech features across visual and auditory senses with a smooth sensation of unified memory. The aim of this study was to investigate how the fine-grained synchrony between coinciding visual and auditory features impacts brain oscillations when forming multisensory speech memories. We developed a memory task presenting participants with short synchronous or asynchronous movie clips focused on the face of speakers in real interviews, all the while undergoing magnetoencephalography recording. In the synchronous condition, the natural alignment between visual and auditory onsets was kept intact. In the asynchronous condition, auditory onsets were delayed to present lip movements and speech sounds in antiphase specifically with respect to the theta oscillation synchronizing them in the original movie. Our results first showed that theta oscillations in the neocortex and hippocampus were modulated by the level of synchrony between lip movements and syllables during audiovisual speech perception. Second, theta asynchrony between the lip movements and auditory envelope during audiovisual speech perception reduced the accuracy of subsequent theta oscillation reinstatement during memory recollection. We conclude that neural theta oscillations play a pivotal role in both audiovisual integration and memory replay of speech.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12096043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102940","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}