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Neural encoding of direction and distance across reference frames in visually guided reaching. 视觉引导伸手过程中跨参照系方向和距离的神经编码
IF 2.7 3区 医学
eNeuro Pub Date : 2024-11-18 DOI: 10.1523/ENEURO.0405-24.2024
Alejandra Harris Caceres, Deborah A Barany, Neil M Dundon, Jolinda Smith, Michelle Marneweck
{"title":"Neural encoding of direction and distance across reference frames in visually guided reaching.","authors":"Alejandra Harris Caceres, Deborah A Barany, Neil M Dundon, Jolinda Smith, Michelle Marneweck","doi":"10.1523/ENEURO.0405-24.2024","DOIUrl":"10.1523/ENEURO.0405-24.2024","url":null,"abstract":"<p><p>Goal-directed actions require transforming sensory information into motor plans defined across multiple parameters and reference frames. Substantial evidence supports the encoding of target direction in gaze- and body-centered coordinates within parietal and premotor regions. However, how the brain encodes the equally critical parameter of target distance remains less understood. Here, using Bayesian pattern component modeling of fMRI data during a delayed reach-to-target task, we dissociated the neural encoding of both target direction and the relative distances between target, gaze, and hand at early and late stages of motor planning. This approach revealed independent representations of direction and distance along the human dorsomedial reach pathway. During early planning, most premotor and superior parietal areas encoded a target's distance in single or multiple reference frames and encoded its direction. In contrast, distance encoding was magnified in gaze- and body-centric reference frames during late planning. These results emphasize a flexible and efficient human central nervous system that achieves goals by remapping sensory information related to multiple parameters, such as distance and direction, in the same brain areas.<b>Significance statement</b> Motor plans specify various parameters, e.g., target direction and distance, each of which can be defined in multiple reference frames relative to gaze, limb, or head. Combining fMRI, a delayed reach-to-target task, and Bayesian pattern component modeling, we present evidence for independent goal-relevant representations of direction and distance in multiple reference frames across early and late planning along the dorsomedial reach pathway. Initially, areas encoding distance also encode direction, but later in planning, distance encoding in multiple reference frames was magnified. These results emphasize central nervous system flexibility in transforming movement parameters in multiple reference frames crucial for successful goal-directed actions and have important implications for brain-computer interface technology advances with sensory integration.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
New Vistas for the Relationship between Empathy and Political Ideology. 移情与政治意识形态之间关系的新视野。
IF 2.7 3区 医学
eNeuro Pub Date : 2024-11-18 Print Date: 2024-11-01 DOI: 10.1523/ENEURO.0086-24.2024
Niloufar Zebarjadi, Annika Kluge, Eliyahu Adler, Jonathan Levy
{"title":"New Vistas for the Relationship between Empathy and Political Ideology.","authors":"Niloufar Zebarjadi, Annika Kluge, Eliyahu Adler, Jonathan Levy","doi":"10.1523/ENEURO.0086-24.2024","DOIUrl":"10.1523/ENEURO.0086-24.2024","url":null,"abstract":"<p><p>The study of ideological asymmetries in empathy has consistently yielded inconclusive findings. Yet, until recently these inconsistencies relied exclusively on self-reports, which are known to be prone to biases and inaccuracies when evaluating empathy levels. Very recently, we reported ideological asymmetries in cognitive-affective empathy while relying on neuroimaging for the first time to address this question. In the present investigation which sampled a large cohort of human individuals from two distant countries and neuroimaging sites, we re-examine this question, but this time from the perspective of empathy to physical pain. The results are unambiguous at the neural and behavioral levels and showcase no asymmetry. This finding raises a novel premise: the question of whether empathy is ideologically asymmetrical depends on the targeted component of empathy (e.g., physical pain vs cognitive-affective) and requires explicit but also unobtrusive techniques for the measure of empathy. Moreover, the findings shed new light on another line of research investigating ideological (a)symmetries in physiological responses to vicarious pain, disgust, and threat.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The overexpression of eIF4E decreases oxytocin levels and induces social-cognitive behavioral disorders in mice. eIF4E的过表达会降低催产素水平,并诱发小鼠的社会认知行为障碍。
IF 2.7 3区 医学
eNeuro Pub Date : 2024-11-18 DOI: 10.1523/ENEURO.0387-24.2024
Longsheng Huang, Juan Wang, Sijie Chen, Miao Zhao, Lizhen Zheng, Xinxin Huang, Xin Hong, Jie Kang, Ping Ou
{"title":"The overexpression of eIF4E decreases oxytocin levels and induces social-cognitive behavioral disorders in mice.","authors":"Longsheng Huang, Juan Wang, Sijie Chen, Miao Zhao, Lizhen Zheng, Xinxin Huang, Xin Hong, Jie Kang, Ping Ou","doi":"10.1523/ENEURO.0387-24.2024","DOIUrl":"10.1523/ENEURO.0387-24.2024","url":null,"abstract":"<p><p>Overexpression of the eukaryotic initiation factor 4E (eIF4E) gene has been associated with excessive stereotypic behaviors and reduced sociability, which manifest as autism-like social cognitive deficits. However, the precise mechanisms by which eIF4E overexpression induces insufficiently these autism-like behaviors and the specific brain regions implicated remain insufficiently understood . Oxytocin, a neurotransmitter known for its role in social behavior, has been proposed to modulate certain autism-related symptoms by influencing microglial function and attenuating neuroinflammation. Nonetheless , the contributions of the hippocampus and oxytocin in the content of eIF4E overexpression-induced autistic behaviors remain elucidated . To investigate this issue,esearchers utilized the three-chamber social interaction test, the open field test, and the Morris water maze to evaluate the social cognitive behaviors of the two groups of mice. Additionally, enzyme-linked immunosorbent assay (ELISA), immunofluorescence, Western blotting, and RT-qPCR were employed to quantify oxytocin levels and assess hippocampal microglial activation.The results indicate that overexpression of eIF4E in mice is associated with significant impairments in social cognition, alongside pronounced marked hyperactivation of hippocampal microglia.<b>Significance statement</b> Autism spectrum disorder (ASD) encompasses a range of neurodevelopmental disorders characterized by social cognitive impairment.Research has indicated a correlation between the overexpression of the eukaryotic initiation factor 4E (eIF4E) gene and autism-like social cognitive impairment.Oxytocin (OXT), a neurotransmitter, plays a role in regulating hippocampal microglial activity and attenuating neuroinflammation. This modulation may impact social cognition in individuals with autism.Nevertheless,it remains unclear whether there is an involvement of the hippocampus and oxytocin in autism-like social cognitive impairments due to eIF4E overexpression. The present study suggests that overexpression of eIF4E may induce hyperactivation of microglia and contribute to social cognitive impairment by decreasing oxytocin levels in the hippocampus.These findings offer molecular insights into the manifestation of autism-like behavior resulting from eIF4E overexpression and may guide future clinical interventions.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Impulsive Choices Emerge When the Anterior Cingulate Cortex Fails to Encode Deliberative Strategies. 当前扣带回皮层无法编码慎重策略时会出现冲动性选择
IF 2.7 3区 医学
eNeuro Pub Date : 2024-11-18 Print Date: 2024-11-01 DOI: 10.1523/ENEURO.0379-24.2024
Shelby M White, Mitchell D Morningstar, Emanuela De Falco, David N Linsenbardt, Baofeng Ma, Macedonia A Parks, Cristine L Czachowski, Christopher C Lapish
{"title":"Impulsive Choices Emerge When the Anterior Cingulate Cortex Fails to Encode Deliberative Strategies.","authors":"Shelby M White, Mitchell D Morningstar, Emanuela De Falco, David N Linsenbardt, Baofeng Ma, Macedonia A Parks, Cristine L Czachowski, Christopher C Lapish","doi":"10.1523/ENEURO.0379-24.2024","DOIUrl":"10.1523/ENEURO.0379-24.2024","url":null,"abstract":"<p><p>Impulsive individuals excessively discount the value of delayed rewards, and this is thought to reflect deficits in brain regions critical for impulse control such as the anterior cingulate cortex (ACC). Delay discounting (DD) is an established measure of cognitive impulsivity, referring to the devaluation of rewards delayed in time. This study used male Wistar rats performing a DD task to test the hypothesis that neural activity states in ACC ensembles encode strategies that guide decision-making. Optogenetic silencing of ACC neurons exclusively increased impulsive choices at the 8 s delay by increasing the number of consecutive low-value, immediate choices. In contrast to shorter delays where animals preferred the delay option, no immediate or delay preference was detected at 8 s. These data suggest that ACC was critical for decisions requiring more deliberation between choice options. To address the role of ACC in this process, large-scale multiple single-unit recordings were performed and revealed that 4 and 8 s delays were associated with procedural versus deliberative neural encoding mechanisms, respectively. The 4 and 8 s delay differed in encoding of strategy corresponding to immediate and delay run termination. Specifically, neural ensemble states at 4 s were relatively stable throughout the choice but exhibited temporal evolution in state space during the choice epoch that resembled ramping during the 8 s delay. Collectively, these findings indicate that ensemble states in ACC facilitate strategies that guide decision-making, and impulsivity increases with disruptions of deliberative encoding mechanisms.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":"11 11","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pupil Trend Reflects Sub-Optimal Alertness Maintenance Over 10 Seconds in Vigilance and Working Memory Performance: An Exploratory Study. 瞳孔趋势反映了在 10 秒钟内保持警觉和工作记忆表现的次最佳警觉状态:一项探索性研究。
IF 2.7 3区 医学
eNeuro Pub Date : 2024-11-18 DOI: 10.1523/ENEURO.0250-24.2024
Jumpei Yamashita, Hiroki Terashima, Makoto Yoneya, Kazushi Maruya, Haruo Oishi, Takatsune Kumada
{"title":"Pupil Trend Reflects Sub-Optimal Alertness Maintenance Over 10 Seconds in Vigilance and Working Memory Performance: An Exploratory Study.","authors":"Jumpei Yamashita, Hiroki Terashima, Makoto Yoneya, Kazushi Maruya, Haruo Oishi, Takatsune Kumada","doi":"10.1523/ENEURO.0250-24.2024","DOIUrl":"10.1523/ENEURO.0250-24.2024","url":null,"abstract":"<p><p>Maintaining concentration on demanding cognitive tasks, such as vigilance (VG) and working memory (WM) tasks, is crucial for successful task completion. Previous research suggests that internal concentration maintenance fluctuates, potentially declining to sub-optimal states, which can influence trial-by-trial performance in these tasks. However, the timescale of such alertness maintenance, as indicated by slow changes in pupil diameter, has not been thoroughly investigated. This study explored whether \"pupil trends\"-which selectively signal sub-optimal tonic alertness maintenance at various timescales-negatively correlate with trial-by-trial performance in VG and WM tasks. Using the Psychomotor Vigilance Task (VG) and the Visual-Spatial 2-back Task (WM), we found that human pupil trends lasting over 10 seconds were significantly higher in trials with longer reaction times, indicating poorer performance, compared to shorter reaction time trials, which indicated better performance. The Attention Network Test further validated that these slow trends reflect sub-optimal states related to (tonic) alertness maintenance rather than sub-optimal performance specific to VG and WM tasks, which is more associated with (phasic) responses to instantaneous interference. These findings highlight the potential role of detecting and compensating for non-optimal states in VG and WM performance, significantly beyond the 10-second timescale. Additionally, the findings suggest the possibility of estimating human concentration during various visual tasks, even when rapid pupil changes occur due to luminance fluctuations.<b>Significance Statement</b> Using biomarkers to estimate human concentration levels can adaptively enhance performance in daily activities. Theoretically, the pupil diameter, which measurably fluctuates over several seconds, could mirror real-time concentration in demanding tasks like vigilance (VG) and working memory (WM). Although capable of accurately estimating concentration in the presence of rapid luminance changes, empirical evidence linking these pupil measures at the slow timescales to trial-by-trial VG and WM task performance is lacking. This study demonstrates that the 10-second pupil trend accurately reflects these tasks' performance, underscoring its potential for daily concentration assessment.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dissociable effects of urgency and evidence accumulation during reaching revealed by dynamic multisensory integration. 动态多感官整合揭示了伸手过程中紧迫性和证据积累的不同影响。
IF 2.7 3区 医学
eNeuro Pub Date : 2024-11-14 DOI: 10.1523/ENEURO.0262-24.2024
Anne H Hoffmann, Frédéric Crevecoeur
{"title":"Dissociable effects of urgency and evidence accumulation during reaching revealed by dynamic multisensory integration.","authors":"Anne H Hoffmann, Frédéric Crevecoeur","doi":"10.1523/ENEURO.0262-24.2024","DOIUrl":"10.1523/ENEURO.0262-24.2024","url":null,"abstract":"<p><p>When making perceptual decisions, humans combine information across sensory modalities dependent on their respective uncertainties. However, it remains unknown how the brain integrates multisensory feedback during movement, and which factors besides sensory uncertainty influence sensory contributions. We performed two reaching experiments on healthy adults to investigate whether movement corrections to combined visual and mechanical perturbations scale with visual uncertainty. To describe the dynamics of multimodal feedback responses, we further varied movement time and visual feedback duration during the movement. The results of our first experiment show that the contribution of visual feedback decreased with uncertainty. Additionally, we observed a transient phase during which visual feedback responses were stronger during faster movements. In a follow-up experiment, we found that the contribution of vision increased more quickly during slow movements when we presented the visual feedback for a longer time. Muscle activity corresponding to these visual responses exhibited modulations with sensory uncertainty and movement speed ca. 100ms following the onset of the visual feedback. Using an optimal feedback control model, we show that the increased response to visual feedback during fast movements can be explained by an urgency-dependent increase in control gains. Further, the fact that a longer viewing duration increased the visual contributions suggests that the brain accumulates sensory information over time to estimate the state of the arm during reaching. Our results provide additional evidence concerning the link between reaching control and decision-making, both of which appear to be influenced by sensory evidence accumulation and response urgency.<b>Significance statement</b> The time-course of multisensory integration during movement, along with the factors influencing this process, still requires further investigation. Here, we tested how visual uncertainty, movement speed, and visual feedback duration influence reach corrections to combined visual and mechanical perturbations. Using an optimal feedback control model, we illustrate that the time-course of multimodal corrections follows the predictions of a Kalman filter which continuously weighs sensory feedback and internal predictions according to their reliability. Importantly, we further show that changes in movement speed led to urgency-dependent modulations of control gains. Our results corroborate previous research linking motor control and decision-making by highlighting that multisensory feedback responses depend on sensory evidence accumulation and response urgency in a similar way as decision-making processes.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
State dependent motor cortex stimulation reveals distinct mechanisms for corticospinal excitability and cortical responses. 与状态相关的运动皮层刺激揭示了皮质脊髓兴奋性和皮层反应的不同机制。
IF 2.7 3区 医学
eNeuro Pub Date : 2024-11-14 DOI: 10.1523/ENEURO.0450-24.2024
Nipun D Perera, Miles Wischnewski, Ivan Alekseichuk, Sina Shirinpour, Alexander Opitz
{"title":"State dependent motor cortex stimulation reveals distinct mechanisms for corticospinal excitability and cortical responses.","authors":"Nipun D Perera, Miles Wischnewski, Ivan Alekseichuk, Sina Shirinpour, Alexander Opitz","doi":"10.1523/ENEURO.0450-24.2024","DOIUrl":"https://doi.org/10.1523/ENEURO.0450-24.2024","url":null,"abstract":"<p><p>Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation method that modulates brain activity by inducing electric fields in the brain. Real-time, state-dependent stimulation with TMS has shown that neural oscillation phase modulates corticospinal excitability. However, such motor-evoked potentials (MEPs) only indirectly reflect motor cortex activation and are unavailable at other brain regions of interest. The direct and secondary cortical effects of phase-dependent brain stimulation remain an open question. In this study, we recorded the cortical responses during single-pulse TMS using electroencephalography (EEG) concurrently with the MEP measurements in 20 healthy human volunteers (11 female). TMS was delivered at peak, rising, trough, and falling phases of mu (8-13 Hz) and beta (14-30 Hz) oscillations in the motor cortex. The cortical responses were quantified through TMS-evoked potential components N15, P50, and N100 as peak-to-peak amplitudes (P50-N15 and P50-N100). We further analyzed whether the pre-stimulus frequency band power was predictive of the cortical responses. We demonstrated that phase-specific targeting modulates cortical responses. The phase relationship between cortical responses was different for early and late responses. In addition, pre-TMS mu oscillatory power and phase significantly predicted both early and late cortical EEG responses in mu-specific targeting, indicating the independent causal effects of phase and power. However, only pre-TMS beta power significantly predicted the early and late TEP components during beta-specific targeting. Further analyses indicated distinct roles of mu and beta power on cortical responses. These findings provide insight to mechanistic understanding of neural oscillation states in cortical and corticospinal activation in humans.<b>Significance Statement</b> Understanding the effects of noninvasive neuromodulation on human brain provides valuable insights to its clinical utility. Brain state dependent stimulation helps us understand mechanisms leading to cortical responses and behavioral outcomes. Here we study the effects of the phase of ongoing oscillations in the motor cortex on cortical responses measured by electroencephalography. We also studied the relationship of phase preference between cortical responses and motor evoked potentials. Furthermore, we investigated the effects of the power of ongoing oscillations on cortical responses. These findings are important to understand the changes in biomarkers during state-dependent brain stimulation and their relationship to behavioral outcomes. At large, this helps the researchers to utilize state-dependent brain stimulation to enhance treatment efficacy.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Erratum: White et al., "Learning to Choose: Behavioral Dynamics Underlying the Initial Acquisition of Decision-Making". 勘误:White 等人,"学会选择:决策的初始习得所依赖的行为动力"。
IF 2.7 3区 医学
eNeuro Pub Date : 2024-11-14 Print Date: 2024-11-01 DOI: 10.1523/ENEURO.0429-24.2024
{"title":"Erratum: White et al., \"Learning to Choose: Behavioral Dynamics Underlying the Initial Acquisition of Decision-Making\".","authors":"","doi":"10.1523/ENEURO.0429-24.2024","DOIUrl":"10.1523/ENEURO.0429-24.2024","url":null,"abstract":"","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":"11 11","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11567142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Normal pressure hydrocephalus in adult mice causes gait impairment, cognitive deficits, and urinary frequency with incontinence. 成年小鼠的正常压力脑积水会导致步态障碍、认知障碍和尿频尿失禁。
IF 2.7 3区 医学
eNeuro Pub Date : 2024-11-14 DOI: 10.1523/ENEURO.0412-24.2024
Margaret M Tish, Natalie A Voss, Aimee X Bertolli, Miles J Klimara, Richard J Smith, Daniel R Thedens, Chantal Allamargot, Marco M Hefti, Matthew A Howard, Georgina M Aldridge, Joel C Geerling
{"title":"Normal pressure hydrocephalus in adult mice causes gait impairment, cognitive deficits, and urinary frequency with incontinence.","authors":"Margaret M Tish, Natalie A Voss, Aimee X Bertolli, Miles J Klimara, Richard J Smith, Daniel R Thedens, Chantal Allamargot, Marco M Hefti, Matthew A Howard, Georgina M Aldridge, Joel C Geerling","doi":"10.1523/ENEURO.0412-24.2024","DOIUrl":"10.1523/ENEURO.0412-24.2024","url":null,"abstract":"<p><p>Normal pressure hydrocephalus (NPH) is marked by enlarged cerebral ventricles with normal intracranial pressure, plus three stereotypical symptoms: gait impairment, cognitive dysfunction, and urinary frequency with urge-incontinence. The neural circuit dysfunction responsible for each of these symptoms remains unknown, and an adult mouse model would expand opportunities to explore these mechanisms in preclinical experiments. Here, we describe the first mouse model of chronic, communicating hydrocephalus with normal intracranial pressure. Hydrocephalic male and female mice had unsteady gait and reduced maximum velocity. Despite performing well on a variety of behavioral tests, they exhibited subtle learning impairments. Hydrocephalic mice also developed urinary frequency, and many became incontinent. This mouse model, with symptoms resembling human NPH, can be combined with molecular-genetic tools in any mouse strain to explore the neural circuit mechanisms of these symptoms. Preclinical work using this hydrocephalus model will lead to the development of new treatments for NPH symptoms.<b>Significance Statement</b> Like human patients with normal pressure hydrocephalus (NPH), mice with communicating hydrocephalus develop enlarged cerebral ventricles with normal intracranial pressure plus three stereotypical symptoms: gait impairment, cognitive dysfunction, and urinary frequency with incontinence. This mouse model, with symptoms resembling human NPH, can be combined with molecular-genetic tools in any mouse strain to explore neural circuit mechanisms of NPH symptoms.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Prenatal Exposure to MAM Impairs mPFC and Hippocampal Inhibitory Function in Mice during Adolescence and Adulthood. 产前接触 MAM 会损害小鼠青春期和成年期的 mPFC 和海马抑制功能。
IF 4.6 3区 医学
eNeuro Pub Date : 2024-11-14 Print Date: 2024-11-01 DOI: 10.1523/ENEURO.0362-24.2024
Zhiyin He, Qian He, Xiaorong Tang, Keni Huang, Yiwen Lin, Jianrui Xu, Qiliang Chen, Nenggui Xu, Lulu Yao
{"title":"Prenatal Exposure to MAM Impairs mPFC and Hippocampal Inhibitory Function in Mice during Adolescence and Adulthood.","authors":"Zhiyin He, Qian He, Xiaorong Tang, Keni Huang, Yiwen Lin, Jianrui Xu, Qiliang Chen, Nenggui Xu, Lulu Yao","doi":"10.1523/ENEURO.0362-24.2024","DOIUrl":"10.1523/ENEURO.0362-24.2024","url":null,"abstract":"<p><p>Neurodevelopmental abnormalities are considered to be one of the important causes of schizophrenia. The offspring of methylazoxymethanol acetate (MAM)-exposed mice are recognized for the dysregulation of neurodevelopment and are well-characterized with schizophrenia-like phenotypes. However, the inhibition-related properties of the medial prefrontal cortex (mPFC) and hippocampus throughout adolescence and adulthood have not been systematically elucidated. In this study, both 10 and 15 mg/kg MAM-exposed mice exhibited schizophrenia-related phenotypes in both adolescence and adulthood, including spontaneous locomotion hyperactivity and deficits in prepulse inhibition. We observed that there was an obvious parvalbumin (PV) loss in the mPFC and hippocampus of MAM-exposed mice, extending from adolescence to adulthood. Moreover, the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) in pyramidal neurons at mPFC and hippocampus was significantly dampened in the 10 and 15 mg/kg MAM-exposed mice. Furthermore, the firing rate of putative pyramidal neurons in mPFC and hippocampus was increased, while that of putative inhibitory neurons was decreased during both adolescence and adulthood. In conclusion, PV loss in mPFC and hippocampus of MAM-exposed mice may contribute to the impaired inhibitory function leading to the attenuation of inhibition in the brain both in vitro and in vivo.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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