Progress in Neurobiology最新文献_第4页

Neural dynamics encoding risky choices during deliberation reveal separate choice subspaces 在审议过程中编码风险选择的神经动力学揭示了单独的选择子空间。

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2025-05-07 DOI: 10.1016/j.pneurobio.2025.102776

Logan M. Peters , Alec Roadarmel , Jacqueline A. Overton , Matthew P. Stickle , Zhaodon Kong , Ignacio Saez , Karen Anne Moxon

{"title":"Neural dynamics encoding risky choices during deliberation reveal separate choice subspaces","authors":"Logan M. Peters , Alec Roadarmel , Jacqueline A. Overton , Matthew P. Stickle , Zhaodon Kong , Ignacio Saez , Karen Anne Moxon","doi":"10.1016/j.pneurobio.2025.102776","DOIUrl":"10.1016/j.pneurobio.2025.102776","url":null,"abstract":"<div><div>Human decision-making involves the coordinated activity of multiple brain areas, acting in concert, to enable humans to make choices. Most decisions are carried out under conditions of uncertainty, where the desired outcome may not be achieved if the wrong decision is made. In these cases, humans deliberate before making a choice. The neural dynamics underlying deliberation are unknown and intracranial recordings in clinical settings present a unique opportunity to record high temporal resolution electrophysiological data from many (hundreds) brain locations during behavior. Combined with dynamic systems modeling, these allow identification of latent brain states that describe the neural dynamics during decision-making, providing insight into these neural dynamics and computations. Results show that the neural dynamics underlying risky decisions, but not decisions without risk, converge to separate subspaces depending on the subject’s preferred choice and that the degree of overlap between these subspaces declines as choice approaches, suggesting a network level representation of evidence accumulation. These results bridge the gap between regression analyses and data driven models of latent states and suggest that during risky decisions, deliberation and evidence accumulation toward a final decision are represented by the same neural dynamics, providing novel insights into the neural computations underlying human choice.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"250 ","pages":"Article 102776"},"PeriodicalIF":6.7,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144022247","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}

引用次数: 0

Bidirectional control of generalized absence epilepsy networks via real-time direct depolarization of thalamocortical neurons 通过丘脑皮质神经元实时直接去极化双向控制广泛性缺失癫痫网络。

IF 6.1 2区医学

Progress in Neurobiology Pub Date : 2025-05-06 DOI: 10.1016/j.pneurobio.2025.102774

Tatiana P. Morais , Hannah L. Taylor , Olivér Nagy , Ferenc Mátyás , Francois David , Vincenzo Crunelli , Magor L. Lőrincz

{"title":"Bidirectional control of generalized absence epilepsy networks via real-time direct depolarization of thalamocortical neurons","authors":"Tatiana P. Morais , Hannah L. Taylor , Olivér Nagy , Ferenc Mátyás , Francois David , Vincenzo Crunelli , Magor L. Lőrincz","doi":"10.1016/j.pneurobio.2025.102774","DOIUrl":"10.1016/j.pneurobio.2025.102774","url":null,"abstract":"<div><div>Absence seizures (ASs), characterized by bilateral spike-and-wave discharges (SWDs), are a hallmark of idiopathic generalized epilepsies. We investigated the role of thalamocortical (TC) neurons in the generation and termination of ASs using optogenetic techniques in freely behaving GAERS rats, a well-established AS model. We demonstrate that direct depolarization of ChR2-transfected TC neurons in the ventrobasal thalamic nuclei during quiet wakefulness (QW) reliably elicits ethosuximide-sensitive ASs that have similar duration and frequency to those of spontaneous ASs, while showing little and no effect during active wakefulness (AW) and slow wave sleep (SWS), respectively. Light-stimulation of TC neurons fails to elicit ASs during AW, QW and SWS in non-epileptic control (NEC) rats, whereas it could evoke short ASs in Wistar rats, prevalently during QW. Notably, brief light stimulation effectively halted ongoing spontaneous ASs in GAERS rats (i.e. both SWDs and immobility), immediately altering thalamic multi-unit activity from rhythmic to irregular firing, irrespective of the SWD phase at which it was delivered. These findings support the view that the excitability of cortico-thalamic-cortical network is highly behavioural state-dependent, with increased susceptibility to the induction of ASs during QW, thus questioning the necessity of low-threshold burst firing of TC neurons in the generation of these seizures. Moreover, they highlight the dual control of ASs by TC neurons, underscoring their potential as therapeutic targets for AS modulation.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"252 ","pages":"Article 102774"},"PeriodicalIF":6.1,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144043145","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}

引用次数: 0

Temporal impact of sepsis on Alzheimer's disease pathology and neuroinflammation 脓毒症对阿尔茨海默病病理和神经炎症的时间影响

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2025-05-03 DOI: 10.1016/j.pneurobio.2025.102775

Quan Vo , Dina C. Nacionales , Karen N. McFarland , Carmelina Gorski , Evan L. Barrios , Gwoncheol Park , Lyle L. Moldawer , Gemma Casadesus , Ravinder Nagpal , Philip A. Efron , Paramita Chakrabarty

{"title":"Temporal impact of sepsis on Alzheimer's disease pathology and neuroinflammation","authors":"Quan Vo , Dina C. Nacionales , Karen N. McFarland , Carmelina Gorski , Evan L. Barrios , Gwoncheol Park , Lyle L. Moldawer , Gemma Casadesus , Ravinder Nagpal , Philip A. Efron , Paramita Chakrabarty","doi":"10.1016/j.pneurobio.2025.102775","DOIUrl":"10.1016/j.pneurobio.2025.102775","url":null,"abstract":"<div><div>Epidemiological evidence has revealed an associative link between sepsis survivorship and increased risk of dementia, particularly Alzheimer's disease (AD). Paradoxically, population studies show females are less susceptible to sepsis but more vulnerable to post-sepsis dementia. Here, we examined the temporal impacts of sepsis in the context of AD by using an AD-amyloidosis model (TgCRND8) and their wild-type littermates and assessing outcomes at 7 days and 3 months post-sepsis in male and female mice. Following 7-days recovery, the microglia and astrocytes in AD-model mice were largely refractile to the systemic immune stimuli. Notably, the female AD-model mice accumulated higher hippocampal amyloid-beta (Aβ) burden and upregulated AD-type transcriptomic signature at this time. On the other hand, male AD-model mice showed no Aβ changes. At this time, the wild-type post-septic males, but not females, displayed robust astrocytosis, with nominal microgliosis. By 3 months post-sepsis, microgliosis was specifically elevated in wild-type females, indicating a prolonged central immune response. At this time, both male and female AD-model mice showed exacerbated Aβ and anxiety indices. Gene network analysis revealed a stronger immune response in females, while the male response was linked to estrogen receptor (ESR) signaling, with ERα protein upregulated in the brains of post-septic AD-model males. Together, our data highlights a sex-dimorphic temporal response in post-sepsis neuroinflammation, with ESR signaling playing a key role in males, while Aβ burden is affected similarly in both males and females.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"250 ","pages":"Article 102775"},"PeriodicalIF":6.7,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143936942","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}

引用次数: 0

EphB2 receptor tyrosine kinase-mediated excitatory synaptic functions are negatively modulated by MDGA2 MDGA2负向调节EphB2受体酪氨酸激酶介导的兴奋性突触功能

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2025-05-01 DOI: 10.1016/j.pneurobio.2025.102772

Hyeonho Kim , Younghyeon Jeon , Seunghye Kim , Yuxuan Guo , Dongwook Kim , Gyubin Jang , Julia Brasch , Ji Won Um , Jaewon Ko

{"title":"EphB2 receptor tyrosine kinase-mediated excitatory synaptic functions are negatively modulated by MDGA2","authors":"Hyeonho Kim , Younghyeon Jeon , Seunghye Kim , Yuxuan Guo , Dongwook Kim , Gyubin Jang , Julia Brasch , Ji Won Um , Jaewon Ko","doi":"10.1016/j.pneurobio.2025.102772","DOIUrl":"10.1016/j.pneurobio.2025.102772","url":null,"abstract":"<div><div>MDGA2 is an excitatory synapse-specific suppressor that uses distinct extracellular mechanisms to negatively regulate various postsynaptic properties. Here, we identify EphB2, an excitatory synapse-specific receptor tyrosine kinase, as a new binding partner for MDGA2. The first three immunoglobulin domains of MDGA2 undergo <em>cis</em>-binding to the ligand-binding domain of EphB2, enabling MDGA2 to compete with Ephrin-B1 for binding to EphB2. Moreover, EphB2 forms complexes with MDGA2 and GluN2B-containing NMDA receptors (NMDARs) in mouse brains. MDGA2 deletion promotes formation of the EphB2/Ephrin-B1 complex but does not alter the surface expression levels and Ephrin-stimulated activation of EphB2 receptors and downstream GluN2B-containing NMDARs in cultured neurons. AlphaFold-based molecular replacement experiments reveal that MDGA2 must bind EphB2 to suppress spontaneous synaptic transmission and NMDAR-mediated, but not AMPAR-mediated, postsynaptic responses at excitatory synapses in cultured neurons. These results collectively suggest that MDGA2 is a versatile factor that suppresses distinct excitatory postsynaptic properties via different transsynaptic pathways.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"250 ","pages":"Article 102772"},"PeriodicalIF":6.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906877","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}

引用次数: 0

Glycine-gated extrasynaptic NMDARs activated during glutamate spillover drive burst firing in nigral dopamine neurons 甘氨酸门控的突触外NMDARs在谷氨酸溢出驱动的突发放电中激活

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2025-04-26 DOI: 10.1016/j.pneurobio.2025.102773

Sofian Ringlet , Zoraide Motta , Laura Vandries , Vincent Seutin , Kevin Jehasse , Laura Caldinelli , Loredano Pollegioni , Dominique Engel

{"title":"Glycine-gated extrasynaptic NMDARs activated during glutamate spillover drive burst firing in nigral dopamine neurons","authors":"Sofian Ringlet , Zoraide Motta , Laura Vandries , Vincent Seutin , Kevin Jehasse , Laura Caldinelli , Loredano Pollegioni , Dominique Engel","doi":"10.1016/j.pneurobio.2025.102773","DOIUrl":"10.1016/j.pneurobio.2025.102773","url":null,"abstract":"<div><div>Burst firing in substantia nigra pars compacta dopamine neurons is a critical biomarker temporally associated to movement initiation. This phasic change is generated by the tonic activation of NMDARs but the respective role of synaptic versus extrasynaptic NMDARs in the ignition of a burst and what is their level of activation remains unknown. Using ex vivo electrophysiological recordings from adolescent rats, we demonstrate that extrasynaptic NMDARs are the primary driver of burst firing. This pool of receptors is recruited during intense synaptic activity via spillover of glutamate and require the binding of NMDAR co-agonist glycine for full activation. Basal synaptic transmission activating only synaptic NMDARs with the support of D-serine is insufficient to generate a burst. Notably, both synaptic and extrasynaptic NMDARs share the same subunit composition but are regulated by distinct co-agonists. Location of NMDARs and regionalization of co-agonists but not NMDAR subunit composition underly burst generation and may serve as a guideline in understanding the physiological role of dopamine in signaling movement.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"249 ","pages":"Article 102773"},"PeriodicalIF":6.7,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143881428","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}

引用次数: 0

Whole-brain effective connectivity of the sensorimotor system using 7 T fMRI with electrical microstimulation in non-human primates 使用7 T功能磁共振成像与电微刺激在非人类灵长类动物的感觉运动系统的全脑有效连接

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2025-04-23 DOI: 10.1016/j.pneurobio.2025.102760

Min-Jun Han , Younghyun Oh , Yejin Ann , Sangyun Kang , Eunha Baeg , Seok Jun Hong , Hansem Sohn , Seong-Gi Kim

{"title":"Whole-brain effective connectivity of the sensorimotor system using 7 T fMRI with electrical microstimulation in non-human primates","authors":"Min-Jun Han , Younghyun Oh , Yejin Ann , Sangyun Kang , Eunha Baeg , Seok Jun Hong , Hansem Sohn , Seong-Gi Kim","doi":"10.1016/j.pneurobio.2025.102760","DOIUrl":"10.1016/j.pneurobio.2025.102760","url":null,"abstract":"<div><div>The sensorimotor system is a crucial interface between the brain and the environment, and it is endowed with multiple computational mechanisms that enable efficient behaviors. For example, predictive processing via an efference copy of a motor command has been proposed as one of the key computations used to compensate for the sensory consequence of movement. However, the neural pathways underlying this process remain unclear, particularly regarding whether the M1-to-S1 pathway plays a dominant role in predictive processing and how its influence compares to that of other pathways. In this study, we present a causally inferable input–output map of the sensorimotor effective connectivity that we made by combining ultrahigh-field functional MRI, electrical microstimulation of the S1/M1 cortex, and dynamic causal modeling for the whole sensorimotor network in anesthetized primates. We investigated how motor signals from M1 are transmitted to S1 at the circuit level, either via direct cortico-cortical projections or indirectly via subcortical structures such as the thalamus. Across different stimulation conditions, we observed a robust asymmetric connectivity from M1 to S1 that was also the most prominent output from M1. In the thalamus, we identified distinct activations: M1 stimulation showed connections to the anterior part of ventral thalamic nuclei, whereas S1 was linked to the more posterior regions of the ventral thalamic nuclei. These findings suggest that the cortico-cortical projection from M1 to S1, rather than the cortico-thalamic loop, plays a dominant role in transmitting movement-related information. Together, our detailed dissection of the sensorimotor circuitry underscores the importance of M1-to-S1 connectivity in sensorimotor coordination.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"250 ","pages":"Article 102760"},"PeriodicalIF":6.7,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906878","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}

引用次数: 0

Slumber under pressure: REM sleep and stress response 压力下的睡眠：快速眼动睡眠和应激反应

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2025-04-22 DOI: 10.1016/j.pneurobio.2025.102771

Bernhard Schaefke , Jingfei Li , Binghao Zhao , Liping Wang , Yu-Ting Tseng

引用次数: 0

Modulation of premotor cortex excitability mitigates the behavioral and electrophysiological abnormalities in a Parkinson's disease mouse model 运动前皮层兴奋性的调节减轻了帕金森病小鼠模型的行为和电生理异常

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2025-04-19 DOI: 10.1016/j.pneurobio.2025.102761

In Sun Choi , Jinmo Kim , Joon Ho Choi , Eun-Mee Kim , Ji-Woong Choi , Jong-Cheol Rah

{"title":"Modulation of premotor cortex excitability mitigates the behavioral and electrophysiological abnormalities in a Parkinson's disease mouse model","authors":"In Sun Choi , Jinmo Kim , Joon Ho Choi , Eun-Mee Kim , Ji-Woong Choi , Jong-Cheol Rah","doi":"10.1016/j.pneurobio.2025.102761","DOIUrl":"10.1016/j.pneurobio.2025.102761","url":null,"abstract":"<div><div>The subthalamic nucleus (STN) plays a crucial role in suppressing prepotent response tendency. The prefrontal regions innervating the STN exhibit increased activity during the stop-signal responses, and the optogenetic activation of these neurons suppresses ongoing behavior. High-frequency electrical stimulation of the STN effectively treats the motor symptoms of Parkinson's disease (PD), yet its underlying circuit mechanisms remain unclear. Here, we investigated the involvement of STN-projecting premotor (M2) neurons in PD mouse models and the impact of deep brain stimulation targeting the STN (DBS-STN). We found that the M2 neurons exhibited enhanced burst firing and synchronous oscillations in the PD mouse model. Remarkably, high-frequency stimulation of STN-projecting M2 neurons, simulating antidromic activation during DBS-STN relieved motor symptoms and hyperexcitability. These changes were attributed to reduced firing frequency vs. current relationship through normalized hyperpolarization-activated inward current (Ih). The M2 neurons in the PD model mouse displayed increased Ih, which was reversed by high-frequency stimulation. Additionally, the infusion of ZD7288, an HCN channel blocker, into the M2 replicated the effects of high-frequency stimulation. In conclusion, our study reveals excessive excitability and suppressive motor control through M2-STN synapses in a PD mouse model. Antidromic excitation of M2 neurons during DBS-STN alleviates this suppression, thereby improving motor impairment. These findings provide insights into the circuit-level dynamics underlying deep brain stimulation's therapeutic effects in PD, suggesting that M2-STN synapses could serve as potential targets for future therapeutic strategies.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"249 ","pages":"Article 102761"},"PeriodicalIF":6.7,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143874020","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}

引用次数: 0

Lethal Interactions of neuronal networks in epilepsy mediated by both synaptic and volume transmission indicate approaches to prevention 由突触和体积传递介导的癫痫中神经元网络的致命相互作用表明了预防的方法

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2025-04-19 DOI: 10.1016/j.pneurobio.2025.102770

Carl L. Faingold

{"title":"Lethal Interactions of neuronal networks in epilepsy mediated by both synaptic and volume transmission indicate approaches to prevention","authors":"Carl L. Faingold","doi":"10.1016/j.pneurobio.2025.102770","DOIUrl":"10.1016/j.pneurobio.2025.102770","url":null,"abstract":"<div><div>Neuronal network interactions are important in normal brain physiology and also in brain disorders. Many mesoscopic networks, including the auditory and respiratory network, mediate a single brain function. Macroscopic networks, including the locomotor network, central autonomic network (CAN), and many seizure networks involve interactions among multiple mesoscopic networks. Network interactions are mediated by neuroactive substances, acting via synaptic transmission, which mediate rapid interactions between networks. Slower, but vitally important network interactions, are mediated by volume transmission. Changes in the interactions between networks, mediated by neuroactive substances, can significantly alter network function and interactions. The acoustic startle response involves interactions between auditory and locomotor networks, and also includes brainstem reticular formation (BRF) nuclei, which participate in many different networks. In the fear-potentiated startle paradigm this network interacts positively with the amygdala, induced by conditioning. Seizure networks can interact negatively with the respiratory network, which becomes lethal in sudden unexpected death in epilepsy (SUDEP), a tragic emergent property of the seizure network. SUDEP models that exhibit audiogenic seizures (AGSz) involve interactions between the auditory and locomotor networks with BRF nuclei. In the DBA/1 mouse SUDEP model the AGSz network interacts negatively with the respiratory network, resulting in postictal apnea. The apnea is lethal unless the CAN is able to initiate autoresuscitation. These network interactions involve synaptic transmission, mediated by GABA and glutamate and volume transmission mediated by adenosine, CO<sub>2</sub> and serotonin. Altering these interaction mechanisms may prevent SUDEP. These epilepsy network interactions illustrate the complex mechanisms that can occur among neuronal networks.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"249 ","pages":"Article 102770"},"PeriodicalIF":6.7,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143858694","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}

引用次数: 0

Neural connections and molecular mechanisms underlying motor skill deficits in genetic models of autism spectrum disorders 自闭症谱系障碍遗传模型中运动技能缺陷的神经连接和分子机制

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2025-04-18 DOI: 10.1016/j.pneurobio.2025.102759

Jingwen Duan , Deyang Zeng , Tong Wu , Zhenzhao Luo , Geng Jingwen , Wei Tan , Yan Zeng

{"title":"Neural connections and molecular mechanisms underlying motor skill deficits in genetic models of autism spectrum disorders","authors":"Jingwen Duan , Deyang Zeng , Tong Wu , Zhenzhao Luo , Geng Jingwen , Wei Tan , Yan Zeng","doi":"10.1016/j.pneurobio.2025.102759","DOIUrl":"10.1016/j.pneurobio.2025.102759","url":null,"abstract":"<div><div>Autism spectrum disorders (ASDs) comprise a broad category of neurodevelopmental disorders that include repetitive behaviors and difficulties in social interactions. Notably, individuals with ASDs exhibit significant impairments in motor skills even prior to the manifestation of other core symptoms. These skills are crucial for daily activities, such as communication, imitation, and exploration, and hold significant importance for individuals with ASDs. This review seeks to offer new insights into the understanding of motor skill impairments by delineating the pathological mechanisms underlying motor skill learning impairments associated with gene mutations in <em>Fmr1</em>, <em>Chd8</em>, <em>Shank3</em>, <em>BTBR</em>, 16p11.2, and <em>Mecp2</em>, predominantly drawing from well-characterized genetic mouse model studies and proposing potential targets for future therapeutic interventions. We further discuss the underlying pathogenic abnormalities associated with the development of specific brain regions within the cerebellum and cerebrum, as well as disruptions in the structure and function of critical neuronal connectivity pathways. Additional research utilizing epidemiological data, clinical observations, and animal research methodologies is warranted to enhance our understanding of the effect of motor skill learning on the growth, development, and social integration of children. Ultimately, our review suggests potential targets for future therapeutic interventions.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"249 ","pages":"Article 102759"},"PeriodicalIF":6.7,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143864311","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}

引用次数: 0