Journal of Neuroscience最新文献

{"title":"Estrogen-regulated lateral septal kisspeptin neurons abundantly project to GnRH neurons and the hypothalamic supramammillary nucleus.","authors":"Soma Szentkirályi-Tóth, Balázs Göcz, Szabolcs Takács, Miklós Sárvári, Imre Farkas, Katalin Skrapits, Éva Rumpler, Szilárd Póliska, Gergely Rácz, András Matolcsy, Gaëtan Ternier, Daniela Fernandois, Paolo Giacobini, Vincent Prévot, William H Colledge, Gábor Wittmann, Andrea Kádár, Petra Mohácsik, Balázs Gereben, Csaba Fekete, Erik Hrabovszky","doi":"10.1523/JNEUROSCI.1307-24.2024","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.1307-24.2024","url":null,"abstract":"<p><p>While hypothalamic kisspeptin (KP) neurons play well-established roles in the estrogen-dependent regulation of reproduction, little is known about extrahypothalamic KP-producing (KP<sub>LS</sub>) neurons of the lateral septum. As established previously, <i>Kiss1</i> expression in this region is low and regulated by estrogen receptor- and GABA<sub>B</sub> receptor-dependent mechanisms. Our present experiments on <i>Kiss1-Cre/ZsGreen</i> knock-in mice revealed that transgene expression in the LS begins at P33-36 in females and P40-45 in males and is stimulated by estrogen receptor signaling. Fluorescent cell numbers continue to increase in adulthood and, regardless of age, remain higher in females. Viral tracing uncovered that the bulk of KP<sub>LS</sub> fibers joins the medial forebrain bundle and terminates in the hypothalamic supramammillary nucleus. Smaller subsets of the axons innervate the medial amygdala or project to other limbic structures. One-quarter of gonadotropin-releasing hormone-immunoreactive perikarya in the preoptic area and their dendrites receive appositions from KP<sub>LS</sub> axons. Ovariectomized adult <i>Kiss1-Cre/ZsGreen</i> mice treated for 4 days with 17β-estradiol or vehicle were used for RNA-Seq studies of laser-microdissected KP<sub>LS</sub> neurons. The transcriptome included markers of GABAergic and neuropeptidergic (<i>Penk</i>, <i>Cartpt, Vgf)</i> cotransmission and 571 estrogen-regulated transcripts. Estrogen treatment upregulated the acetylcholine receptor transcript <i>Chrm2</i> and, in slice electrophysiology experiments, caused enhanced muscarinic inhibition of KP<sub>LS</sub> neurons. Finally, we provided immunohistochemical evidence for homologous neurons in the <i>post mortem</i> human brain, suggesting that KP<sub>LS</sub> neurons may contribute to evolutionarily conserved regulatory mechanisms. Future studies will need to investigate the putative roles of KP<sub>LS</sub> neurons in the estrogen-dependent control of gonadotropin-releasing hormone neurons and/or various hypothalamic/limbic functions.<b>Significance Statement</b> Gonadotropin-releasing hormone (GnRH) neurons of the hypothalamus stimulate pituitary gonadotropin secretion to promote gonadal functions. Sex steroids of the gonads serve as feedback signals to control the hypothalamic output of GnRH. According to current consensus, steroid feedback is mainly sensed and communicated to the GnRH neuronal system by sex steroid-sensitive hypothalamic cell groups through the neuropeptide kisspeptin.Anatomical, developmental, spatial transcriptomic and electrophysiological characterization of an extrahypothalamic kisspeptin system in this study unveils the previously unexplored contribution of lateral septal kisspeptin cells to the sex-steroid dependent afferent control of GnRH neurons. Identification of analogous kisspeptin neurons in the <i>post mortem</i> human brain suggests that this estrogen dependent system may play an evolutionarily cons","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142923898","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":"Time Course of Orientation Ensemble Representation in the Human Brain.","authors":"Xizi Gong, Tao He, Qian Wang, Junshi Lu, Fang Fang","doi":"10.1523/JNEUROSCI.1688-23.2024","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.1688-23.2024","url":null,"abstract":"<p><p>Natural scenes are filled with groups of similar items. Humans employ ensemble coding to extract the summary statistical information of the environment, thereby enhancing the efficiency of information processing, something particularly useful when observing natural scenes. However, the neural mechanisms underlying the representation of ensemble information in the brain remain elusive. In particular, whether ensemble representation results from the mere summation of individual item representations or it engages other specific processes remains unclear. In this study, we utilized a set of orientation ensembles wherein none of the individual item orientations were the same as the ensemble orientation. We recorded magnetoencephalography (MEG) signals from human participants (both sexes) when they performed an ensemble orientation discrimination task. Time-resolved multivariate pattern analysis (MVPA) and the inverted encoding model (IEM) were employed to unravel the neural mechanisms of the ensemble orientation representation and track its time course. First, we achieved successful decoding of the ensemble orientation, with a high correlation between the decoding and behavioral accuracies. Second, the IEM analysis demonstrated that the representation of the ensemble orientation differed from the sum of the representations of individual item orientations, suggesting that ensemble coding could further modulate orientation representation in the brain. Moreover, using source reconstruction, we showed that the representation of ensemble orientation manifested in early visual areas. Taken together, our findings reveal the emergence of the ensemble representation in the human visual cortex and advance the understanding of how the brain captures and represents ensemble information.<b>Significance Statement</b> Ensemble coding, a cognitive process of extracting summary statistical information from groups of similar items, stands as a pivotal strategy enabling humans to efficiently process complex natural scenes with limited sensory capacities. However, the neural mechanisms of ensemble coding remain largely unknown. Recent modeling studies have predominantly highlighted the importance of the summed activation across all items in ensemble coding. Intriguingly, here, we show that ensemble orientation representation differed from the summed representation of all component item orientations, suggesting that ensemble coding incorporates additional processes beyond mere summation. Additionally, we explore how the ensemble orientation representation per se evolved in the human visual cortex. Our findings significantly extend our understanding of ensemble coding.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922083","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":"Emergence of categorical representations in parietal and ventromedial prefrontal cortex across extended training.","authors":"Zhiya Liu, Yitao Zhang, Chudan Wen, Jingzhao Yuan, Jingxian Zhang, Carol A Seger","doi":"10.1523/JNEUROSCI.1315-24.2024","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.1315-24.2024","url":null,"abstract":"<p><p>How do the neural representations underlying category learning change as skill develops? We examined perceptual category learning using a prototype learning task known to recruit a corticostriatal system including the posterior striatum, motor cortex, visual cortex, and the intraparietal sulcus (IPS). Male and female human participants practiced categorizing stimuli as category members or nonmembers (A versus not-A) across three days, with fMRI data collected at the beginning and end. Univariate analyses found that corticostriatal activity in regions associated with habitual instrumental learning were recruited across both sessions, but activity in regions associated with goal-directed instrumental learning decreased from day 1 to day 3. Multivoxel Pattern Analysis (MVPA) indicated that after training the trained category could be more easily decoded from the IPS when compared with a novel category. Representational Similarity Analysis (RSA) showed development of category representations in IPS and motor cortex. In addition, RSA revealed evidence for category-related representations including prototype representation in the ventromedial prefrontal cortex which may reflect parallel development of schematic memory for the category structure. Overall, the results converge to show how performance of category decisions and representations of the category structure emerge after extensive training across the corticostriatal system underlying perceptual category learning.<b>Significance Statement</b> We compared activity during initial category learning with that after an extended training session and used multivariate methods to characterize representational changes. We found that representations changed in the intraparietal sulcus (IPS) and ventromedial prefrontal cortex (VMPFC). The IPS became sensitive to category membership and distinguished between the trained category and a novel category. The VMPFC showed sensitivity to the prototype as well as other category-related features. In addition, motor cortex coded for category membership decisions and making associated motor responses. Overall our results go beyond previous research that established what brain regions are recruited during the initial phases of perceptual category learning to characterize how category representations emerge as participants become highly skilled.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142923867","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":"Enhanced somatosensory inhibition sharpens hand representation and sensorimotor skills in pianists.","authors":"Masato Hirano, Yudai Kimoto, Sachiko Shiotani, Shinichi Furuya","doi":"10.1523/JNEUROSCI.1486-24.2024","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.1486-24.2024","url":null,"abstract":"<p><p>Dexterous motor skills, like those needed for playing musical instruments and sports, require the somatosensory system to accurately and rapidly process somatosensory information from multiple body parts. This is challenging due to the convergence of afferent inputs from different body parts into a single neuron and the overlapping representation of neighboring body parts in the somatosensory cortices. How do trained individuals, such as pianists and athletes, manage this? Here, a series of five experiments with pianists and nonmusicians (female and male) shows that pianists have enhanced inhibitory function in the somatosensory system, which isolates the processing of somatosensory afferent inputs from each finger. This inhibitory function was assessed using a paired-pulse paradigm of somatosensory evoked potentials in Electroencephalography (EEG), which measures the suppressive effect of a first stimulus (i.e., conditioning stimulus) on the response to a subsequent second stimulus. We found that pianists and nonmusicians showed an inhibitory response to the sequential stimuli to the peripheral somatosensory nerve at the wrist when the conditioning stimulus was intense. However, only pianists exhibited an inhibitory response to a weak conditioning stimulus, indicating enhanced inhibitory function in pianists. Additionally, the conditioning stimulus increased the information content segregating individual fingers represented in the cortical activity evoked by passive finger movements and improved the perception of fast multi-finger sequential movements, specifically for pianists. Our findings provide the first evidence for experience-dependent plasticity in somatosensory inhibitory function and highlight its role in the expert motor performance of pianists.<b>Significant statement</b> Fine motor skills, such as playing musical instruments, rely on the somatosensory system to process somatosensory information from multiple body parts. How does the somatosensory system process inputs from different body parts separately and with less interference? This study discovered enhanced inhibitory function in the somatosensory system of expert pianists, which contributes to isolating finger representation in the somatosensory processing and thereby improve the perception and execution of fast and complex multifinger movements. The present findings demonstrate that extensive musical training strengthens inhibitory processing in the somatosensory system, which underlies pianists' remarkable finger dexterity.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142923897","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":"Nonresolving Neuroinflammation Regulates Axon Regeneration in Chronic Spinal Cord Injury.","authors":"Andrew N Stewart, Christopher C Bosse-Joseph, Reena Kumari, William M Bailey, Kennedy A Park, Victoria K Slone, John C Gensel","doi":"10.1523/JNEUROSCI.1017-24.2024","DOIUrl":"10.1523/JNEUROSCI.1017-24.2024","url":null,"abstract":"<p><p>Chronic spinal cord injury (SCI) lesions retain increased densities of microglia and macrophages. In acute SCI, macrophages induce growth cone collapse and facilitate axon retraction away from lesion boundaries. Little is known about the role of sustained inflammation in chronic SCI or whether chronic inflammation affects regeneration. We used the colony-stimulating factor-1 receptor inhibitor, PLX-5622, to deplete microglia and macrophages months after complete crush SCI in female mice. Transcriptional analyses revealed a significant inflammatory depletion within chronic SCI lesions after PLX-5622 treatment. Both transcriptional analyses and immunohistochemistry revealed that Iba1⁺ cells repopulate to predepleted densities after treatment removal. Neuronal-enriched transcripts were significantly elevated in mice after inflammatory repopulation, but no significant effects were observed with inflammatory depletion alone. Axon densities also significantly increased within the lesion after PLX-5622 treatment and after repopulation. To better examine the effect of chronic inflammation on axon regeneration, we tested PLX-5622 treatment in neuronal-specific phosphatase and tensin homolog protein (PTEN) knock-out (PTEN-KO) mice. PTEN-KO was delivered using spinal injections of retrogradely transported adeno-associated viruses (AAVrg's). PTEN-KO did not further increase axon densities within the lesion beyond the effects induced by PLX-5622. Axons that grew within the lesion were histologically identified as 5-HT⁺ and CGRP⁺, both of which are not robustly transduced by AAVrg's. Our work identified that increased macrophage/microglial densities in the chronic SCI environment may be actively retained by homeostatic mechanisms likely affiliated with a sustained elevated expression of CSF1 and other chemokines. Finally, we identify a novel role of sustained inflammation as a prospective barrier to axon regeneration in chronic SCI.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606855","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":"AMPAR Regulation in Synaptic Plasticity: The Roles of Calcineurin, CK2, and α2δ-1.","authors":"Richard Coca","doi":"10.1523/JNEUROSCI.1703-24.2024","DOIUrl":"10.1523/JNEUROSCI.1703-24.2024","url":null,"abstract":"","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"45 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142916234","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":"Computational and Neural Evidence for Altered Fast and Slow Learning from Losses in Problem Gambling.","authors":"Kiyohito Iigaya, Tobias Larsen, Timothy Fong, John P O'Doherty","doi":"10.1523/JNEUROSCI.0080-24.2024","DOIUrl":"10.1523/JNEUROSCI.0080-24.2024","url":null,"abstract":"<p><p>Learning occurs across multiple timescales, with fast learning crucial for adapting to sudden environmental changes, and slow learning beneficial for extracting robust knowledge from multiple events. Here, we asked if miscalibrated fast vs slow learning can lead to maladaptive decision-making in individuals with problem gambling. We recruited participants with problem gambling (PG; N = 20; 9 female and 11 male) and a recreational gambling control group without any symptoms associated with PG (N = 20; 10 female and 10 male) from the community in Los Angeles, CA. Participants performed a decision-making task involving reward-learning and loss-avoidance while being scanned with fMRI. Using computational model fitting, we found that individuals in the PG group showed evidence for an excessive dependence on slow timescales and a reduced reliance on fast timescales during learning. fMRI data implicated the putamen, an area associated with habit, and medial prefrontal cortex (PFC) in slow loss-value encoding, with significantly more robust encoding in medial PFC in the PG group compared to controls. The PG group also exhibited stronger loss prediction error encoding in the insular cortex. These findings suggest that individuals with PG have an impaired ability to adjust their predictions following losses, manifested by a stronger influence of slow value learning. This impairment could contribute to the behavioral inflexibility of problem gamblers, particularly the persistence in gambling behavior typically observed in those individuals after incurring loss outcomes.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142669951","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":"Optogenetic Control of Dopamine Receptor 2 Reveals a Novel Aspect of Dopaminergic Neurotransmission in Motor Function.","authors":"Hyunbin Kim, Geunhong Park, Hyo Geun Shin, Duwan Kwon, Heejung Kim, In-Yeop Baek, Min-Ho Nam, Il-Joo Cho, Jeongjin Kim, Jihye Seong","doi":"10.1523/JNEUROSCI.1473-24.2024","DOIUrl":"10.1523/JNEUROSCI.1473-24.2024","url":null,"abstract":"<p><p>Dopaminergic neurotransmission plays a crucial role in motor function through the coordination of dopamine receptor (DRD) subtypes, such as DRD1 and DRD2, thus the functional imbalance of these receptors can lead to Parkinson's disease. However, due to the complexity of dopaminergic circuits in the brain, it is limited to investigating the individual functions of each DRD subtype in specific brain regions. Here, we developed a light-responsive chimeric DRD2, OptoDRD2, which can selectively activate DRD2-like signaling pathways with spatiotemporal resolution. OptoDRD2 was designed to include the light-sensitive component of rhodopsin and the intracellular signaling domain of DRD2. Upon illumination with blue light, OptoDRD2 triggered DRD2-like signaling pathways, such as Gαi/o subtype recruitment, a decrease in cAMP levels, and ERK phosphorylation. To explore unknown roles of DRD2 in glutamatergic cell populations of basal ganglia circuitry, OptoDRD2 was genetically expressed in excitatory neurons in lateral globus pallidus (LGP) of the male mouse brain. The optogenetic stimulation of OptoDRD2 in the LGP region affected a wide range of locomotion-related parameters, such as increased frequency of movement and decreased immobility time, resulting in the facilitation of motor function of living male mice. Therefore, our findings indicate a potentially novel role for DRD2 in the excitatory neurons of the LGP region, suggesting that OptoDRD2 can be a valuable tool enabling the investigation of unknown roles of DRD2 at specific cell types or brain regions.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142677640","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":"Human iPSC-Derived MSCs Induce Neurotrophic Effects and Improve Metabolic Activity in Acute Neuronal Injury Models.","authors":"Keiji Kawatani, Genesis Omana Suarez, Ralph B Perkerson, Ephraim E Parent, Toshihiko Nambara, Joshua A Knight, Tammee M Parsons, Kshama Gupta, Francis Shue, Alla Alnobani, Prasanna Vibhute, Hancheng Cai, Hugo Guerrero-Cázares, John A Copland, Alfredo Quiñones-Hinojosa, Takahisa Kanekiyo","doi":"10.1523/JNEUROSCI.0606-24.2024","DOIUrl":"10.1523/JNEUROSCI.0606-24.2024","url":null,"abstract":"<p><p>Mesenchymal stromal cell (MSC) therapy has regenerative potentials to treat various pathological conditions including neurological diseases. MSCs isolated from various organs can differentiate into specific cell types to repair organ damages. However, their paracrine mechanisms are predicted to predominantly mediate their immunomodulatory, proangiogenic, and regenerative properties. While preclinical studies highlight the significant potential of MSC therapy in mitigating neurological damage from stroke and traumatic brain injury, the variability in clinical trial outcomes may stem from the inherent heterogeneity of somatic MSCs. Accumulating evidence has demonstrated that induced pluripotent stem cells (iPSCs) are an ideal alternative resource for the unlimited expansion and biomanufacturing of MSCs. Thus, we investigated how iPSC-derived MSCs (iMSCs) influence properties of iPSC-derived neurons. Our findings demonstrate that the secretome from iMSCs possesses neurotrophic effects, improving neuronal survival and promoting neuronal outgrowth and synaptic activity in vitro. Additionally, the iMSCs enhance metabolic activity via mitochondrial respiration in neurons, both in vitro and in mouse models. Glycolytic pathways also increased following the administration of iMSC secretome to iPSC-derived neurons. Consistently, in vivo experiments showed that intravenous administration of iMSCs compensated for the elevated energetic demand in male mice with irradiation-induced brain injury by restoring synaptic metabolic activity during acute brain damage. ¹⁸F-FDG PET imaging also detected an increase in brain glucose uptake following iMSC administration. Together, our results highlight the potential of iMSC-based therapy in treating neuronal damage in various neurological disorders, while paving the way for future research and potential clinical applications of iMSCs in regenerative medicine.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576646","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":"Cerebellar Purkinje Cell Activity Regulates White Matter Response and Locomotor Function after Neonatal Hypoxia.","authors":"Srikanya Kundu, Javid Ghaemmaghami, Georgios Sanidas, Nora Wolff, Abhya Vij, Chad Byrd, Gabriele Simonti, Maria Triantafyllou, Beata Jablonska, Terry Dean, Ioannis Koutroulis, Vittorio Gallo, Panagiotis Kratimenos","doi":"10.1523/JNEUROSCI.0899-24.2024","DOIUrl":"10.1523/JNEUROSCI.0899-24.2024","url":null,"abstract":"<p><p>Neonatal hypoxia (Hx) causes white matter (WM) injury, particularly in the cerebellum. We previously demonstrated that Hx-induced reduction of cerebellar Purkinje cell (PC) activity results in locomotor deficits. Yet, the mechanism of Hx-induced cerebellar WM injury and associated locomotor abnormalities remains undetermined. Here, we show that the cerebellar WM injury and linked locomotor deficits are driven by PC activity and are reversed when PC activity is restored. Using optogenetics and multielectrode array recordings, we manipulated PC activity and captured the resulting cellular responses in WM oligodendrocyte precursor cells and GABAergic interneurons. To emulate the effects of Hx, we used light-activated halorhodopsin targeted specifically to the PC layer of normal mice. Suppression of PC firing activity at P13 and P21 phenocopied the locomotor deficits observed in Hx. Moreover, histopathologic analysis of the developing cerebellar WM following PC inhibition (P21) revealed a corresponding reduction in oligodendrocyte maturation and myelination, akin to our findings in Hx mice. Conversely, PC stimulation restored PC activity, promoted oligodendrocyte maturation, and enhanced myelination, resulting in reversed Hx-induced locomotor deficits. Our findings highlight the crucial role of PC activity in cerebellar WM development and locomotor performance following neonatal injury.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142548652","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}