Journal of Neuroscience最新文献

{"title":"Leptin activates dopamine and GABA neurons in the substantia nigra via a local pars compacta-pars reticulata circuit.","authors":"Maria Mancini, Takuya Hikima, Paul Witkovsky, Jyoti C Patel, Dominic W Stone, Alison H Affinati, Margaret E Rice","doi":"10.1523/JNEUROSCI.1539-24.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.1539-24.2025","url":null,"abstract":"<p><p>Adipose-derived leptin contributes to energy homeostasis by balancing food intake and motor output, but how leptin acts in brain motor centers remains poorly understood. We investigated the influence of leptin on neuronal activity in two basal ganglia nuclei involved in motor control: the substantia nigra pars compacta (SNc) and pars reticulata (SNr). Using a mouse reporter line to identify cells expressing leptin receptors (LepRs), we found that in both sexes, a majority of SNc dopamine neurons express a high level of LepR. Whole-cell recording in ex vivo midbrain slices from male wild-type mice showed that leptin activates SNc dopamine neurons directly and increases somatodendritic dopamine release. Although LepR expression in SNr GABA output neurons was low, leptin also activated these cells. Additional experiments showed that the influence of leptin on SNr neurons is indirect and involves D1 dopamine receptors and TRPC3 channels. Administration of leptin to male mice increased locomotor activity, consistent with activation of dopamine neurons in the SNc coupled to previously reported amplification of axonal dopamine release by leptin in striatal slices. These findings indicate that in addition to managing energy homeostasis through its actions as a satiety hormone, leptin also promotes axonal and somatodendritic dopamine release that can influence motor output.<b>Significance statement</b> Dopamine neurons regulate motivated behaviors, but how they are influenced by metabolic hormones, like leptin, is incompletely understood. We show here that leptin increases the activity of substantia nigra (SN) pars compacta dopamine neurons directly, and that this enhances somatodendritic dopamine release. Leptin also increases the activity of GABAergic neurons in the SN pars reticulata, but does so indirectly via D1 dopamine receptors activated by locally released dopamine. Consistent with increased nigral dopamine neuron activity and previous evidence showing that leptin amplifies striatal dopamine release, systemic leptin increases locomotor behavior. This increase in motor activity complements the well-established inhibitory effect of leptin on food intake and adds an additional dimension to the regulation of energy balance by this hormone.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702057","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":"Anatomically distinct regions in the inferior frontal cortex are modulated by task and reading skill.","authors":"Hannah L Stone, Jamie L Mitchell, Mia Fuentes-Jimenez, Jasmine E Tran, Jason D Yeatman, Maya Yablonski","doi":"10.1523/JNEUROSCI.1767-24.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.1767-24.2025","url":null,"abstract":"<p><p>Inferior frontal cortex (IFC) is a critical region for reading and language. This part of the cortex is highly heterogeneous in its structural and functional organization and shows high variability across individuals. Despite decades of research, the relationship between specific IFC regions and reading skill remains unclear. To shed light on the function of IFC in reading, we aim to (1) characterize the functional landscape of text-selective responses in IFC, while accounting for interindividual variability; and (2) examine how text-selective regions in the IFC relate to reading proficiency. To this end, children with a wide range of reading ability (N=66; age 7-14 years, 34 female, 32 male) completed functional MRI scans while performing two tasks on text and non-text visual stimuli. Importantly, both tasks do not explicitly require reading, and can be performed on all visual stimuli. This design allows us to tease apart stimulus-driven responses from task-driven responses and examine where in IFC task and stimulus interact. We were able to identify three anatomically-distinct, text-selective clusters of activation in IFC, in the inferior frontal sulcus (IFS), and dorsal and ventral precentral gyrus (PrG). ​​These three regions showed a strong task effect that was highly specific to text. Furthermore, text-selectivity in the IFS and dorsal PrG was associated with reading proficiency, such that better readers showed higher selectivity to text. These findings suggest that text-selective regions in the IFC are sensitive to both stimulus and task, and highlight the importance of this region for proficient reading.<b>Significance statement</b> The inferior frontal cortex (IFC) is a critical region for language processing, yet despite decades of research, its relationship with reading skill remains unclear. In a group of children with a wide range of reading skills, we were able to identify three anatomically distinct text-selective clusters of activation in the IFC. ​​These regions showed a strong task effect that was highly selective to text. Text-selectivity was positively correlated with reading proficiency, such that better readers showed higher selectivity to text, even in tasks that did not require reading. These findings suggest that multiple text-selective regions within IFC are sensitive to both stimulus and task, and highlight the critical role of IFC for reading proficiency.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702013","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":"Overlapping Cortical Substrate of Biomechanical Control and Subjective Agency.","authors":"John P Veillette, Alfred F Chao, Romain Nith, Pedro Lopes, Howard C Nusbaum","doi":"10.1523/JNEUROSCI.1673-24.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.1673-24.2025","url":null,"abstract":"<p><p>Every movement requires the nervous system to solve a complex biomechanical control problem, but this process is mostly veiled from one's conscious awareness. Simultaneously, we also have conscious experience of controlling our movements-our sense of agency (SoA). Whether SoA corresponds to those neural representations that implement actual neuromuscular control is an open question with ethical, medical, and legal implications. If SoA is the conscious experience of control, this predicts that SoA can be decoded from the same brain structures that implement the so-called \"inverse dynamics\" computations for planning movement. We correlated human (male and female) fMRI measurements during hand movements with the internal representations of a deep neural network (DNN) performing the same hand control task in a biomechanical simulation-revealing detailed cortical encodings of sensorimotor states, idiosyncratic to each subject. We then manipulated SoA by usurping control of participants' muscles via electrical stimulation, and found that the same voxels which were best explained by modeled inverse dynamics representations-which, strikingly, were located in canonically visual areas-also predicted SoA. Importantly, model-brain correspondences and robust SoA decoding could both be achieved within single subjects, enabling relationships between motor representations and awareness to be studied at the level of the individual.<b>Significance Statement</b> The inherent complexity of biomechanical control problems is belied by the seeming simplicity of directing movements in our subjective experience. This aspect of our experience suggests we have limited conscious access to the neural and mental representations involved in controlling the body - but of which of the many possible representations are we, in fact, aware? Understanding which motor control representations percolate into awareness has taken on increasing importance as emerging neural interface technologies push the boundaries of human autonomy. In our study, we leverage machine learning models that have learned to control simulated bodies to localize biomechanical control representations in the brain. Then, we show that these brain regions predict perceived agency over the musculature during functional electrical stimulation.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702058","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":"CCKergic Tufted Cells Regulate Odor Sensitivity by Controlling Mitral Cell Output in the Mouse Olfactory Bulb.","authors":"Eric Starr, Rashika Budhathoki, Dylan Gilhooly, Laura Castillo, Meigeng Hu, Dan Zhao, Yaping Li, Shaolin Liu","doi":"10.1523/JNEUROSCI.1243-24.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.1243-24.2025","url":null,"abstract":"<p><p>Despite the importance of odor detection to the survival of most animals, mechanisms governing olfactory sensitivity remain unclear, especially beyond the olfactory sensory neurons (OSNs). Here we leverage opto- and chemo-genetics to selectively modulate activities of CCKergic tufted cells (TCs) in the mouse olfactory bulb (OB) of either sex, which form the intrabulbar associational system (IAS) to link isofunctional glomeruli, to determine the functional impact on OB output via mitral cells (MCs) and odor detection in behaving animals. NMDA receptors in CCKergic TCs remarkably amplify the OSN-evoked monosynaptic responses in these excitatory neurons, which provide a long-lasting feedforward excitation to MCs via both chemical transmission and electrical synapses between their apical dendrites. NMDA receptors in MCs mediate late components of the dendrodendritic TC→MC transmission to significantly boost MC outcome. Congruently, optogenetic inhibition of the CCKerigic TCs dramatically reduces the OSN-evoked MC responses. Unexpectedly, optogenetic activation of the axons projecting from CCKergic TCs on the opposite side of the same bulb produces a mainly AMPA receptor-mediated excitatory responses in MCs, leading us to speculate that CCKergic TCs functionally synchronize MC output from mirror glomeruli. Furthermore, chemogenetic inhibition of CCKergic TCs reduces animal's sensitivity to odors by elevating detection threshold, consistent with the key role of these TCs in functionally controlling MC output. Collectively, our results delineate the cellular and circuit mechanisms allowing the CCKergic TCs to regulate MC output from glomeruli on both medial and lateral side of each OB and the system's sensitivity to odors possibly via the IAS.<b>Significance Statement</b> The detection and processing of chemical stimuli, such as environmental odorants, are essential for the central nervous system to generate appropriate behavioral responses in animals. Most of our current knowledge about odor detection comes from studies on the interactions between chemical stimuli and odorant receptors on olfactory sensory neurons (OSNs) at the periphery. In this study, we have identified a specific subpopulation of nerve cells that play a crucial role in converting sensory input into biological signals within the olfactory bulb, the downstream target of OSNs and the initial site of synaptic odor processing. Our findings provide new insights into the cellular and circuit-level mechanisms that regulate olfactory detection beyond sensory neurons.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702015","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":"Large-Scale High-Resolution Probabilistic Maps of the Human Superior Longitudinal Fasciculus Subdivisions and their Cortical Terminations.","authors":"Matthew Amandola, Katherine Farber, Roma Kidambi, Hoi-Chung Leung","doi":"10.1523/JNEUROSCI.0821-24.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.0821-24.2025","url":null,"abstract":"<p><p>The superior longitudinal fasciculus (SLF) is the large white matter association tract connecting the prefrontal and posterior parietal cortices. Past studies in non-human primates have parcellated the SLF into three subdivisions and have outlined the specific cortico-cortical organization and terminations for each subdivision. However, it is difficult to characterize these structural connections in humans to the specificity of tract-tracing studies in animals. This has led to disagreement on how the SLF subdivisions are organized in the human brain, including if the dorsomedial SLF (SLF-I) is part of the cingulum subsystem. Here, we present a novel large-scale, probabilistic map of the SLF subdivisions, using high-resolution diffusion imaging data from the Human Connectome Project (HCP). We used image data from 302 adult males and 405 adult females to model the three SLF subdivisions in each hemisphere, and attempted to characterize the frontal and parietal termination points for each subdivision. SLF subdivisions were successfully modeled in each subject, showing the dorsomedial-to-ventrolateral organization similar to that in nonhuman primate histological studies. We also found minimal differences between SLF-I models with and without the cingulate gyrus excluded, suggesting that the SLF-I may be a separable tract from the cingulum. Lastly, the SLF subdivisions showed differentiable associations with major cognitive domains such as memory and executive functions. While histological confirmation is needed beyond tractography, these probabilistic masks offer a first step in guiding future exploration of frontoparietal organization by providing detailed characterization of the SLF subdivisions and their potential cortical terminations.<b>Significance statement</b> The prefrontal and posterior parietal areas are interconnected via the SLF, which has been characterized in great detail in monkeys. However, it is difficult to map the SLF organization in the human brain, and previous diffusion MRI findings have been inconsistent. Using diffusion MRI data from 707 individuals, our probabilistic tractography revealed dorsomedial-to-ventrolateral organization of the three SLF subdivisions and their cortical terminations. Our tractography also suggests limited shared volume between the SLF-I and the cingulum, a controversy in recent literature. The SLF subdivisions also differ in their cognitive associations. As a result, we created a large-scale, high-resolution probabilistic parcellation of the SLF, representing an advancement toward standardizing the mapping of human frontoparietal structural connections for clinical and scientific research.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702037","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":"Characterizing Human Disparity Tuning Properties Using Population Receptive Field Mapping.","authors":"Ivan Alvarez, Alessandro Mancari, I Betina Ip, Andrew J Parker, Holly Bridge","doi":"10.1523/JNEUROSCI.0795-24.2025","DOIUrl":"10.1523/JNEUROSCI.0795-24.2025","url":null,"abstract":"<p><p>Our visual percept of small differences in depth is largely informed by binocular stereopsis, the ability to decode depth from the horizontal offset between the retinal images in each eye. While multiple cortical areas are associated with stereoscopic processing, it is unclear how tuning to specific binocular disparities is organized across the human visual cortex. We used 3 T functional magnetic resonance imaging to generate population receptive fields (pRFs) in response to modulation of binocular disparity to characterize the neural tuning to disparity. We also used psychophysics to measure stereoacuity thresholds compared with backgrounds at different depths (pedestal disparity). Ten human participants (seven females) observed correlated or anticorrelated random-dot stereograms with disparity ranging from -0.3 to 0.3°, and responses were modeled as one-dimensional tuning curves along the depth dimension. First, we demonstrate that lateral and dorsal visual areas show the greatest proportion of vertices selective for binocular disparity. Second, with binocularly correlated stimuli, we show a polynomial relationship between preferred disparity and tuning curve width, with sharply tuned disparity responses at near-zero disparities, and broader disparity tuning profiles at near or far disparities. This relationship held across visual areas and was not present for anticorrelated stimuli. Finally, the individual thresholds for psychophysical stereoacuity at the three different pedestal disparities were broadly related to pRF tuning width in area V1, suggesting a possible limit for fine stereopsis at the earliest level of cortical processing. Together, these findings point to heterogeneity of disparity processing across human visual areas, comparable with nonhuman primates.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7617416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371422","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":"Involvement of aSPOC in the Online Updating of Reach-to-Grasp to Mechanical Perturbations of Hand Transport.","authors":"Mariusz P Furmanek, Luis F Schettino, Mathew Yarossi, Madhur Mangalam, Kyle Lockwood, Sergei V Adamovich, Eugene Tunik","doi":"10.1523/JNEUROSCI.0173-24.2025","DOIUrl":"10.1523/JNEUROSCI.0173-24.2025","url":null,"abstract":"<p><p>Humans adjust their movement to changing environments effortlessly via multisensory integration of the effector's state, motor commands, and sensory feedback. It is postulated that frontoparietal (FP) networks are involved in the control of prehension, with dorsomedial (DM) and dorsolateral (DL) regions processing the reach and the grasp, respectively. This study tested (five female and five male participants) the differential involvement of FP nodes [ventral premotor cortex (PMv), dorsal premotor cortex (PMd), anterior intraparietal sulcus (aIPS), and anterior superior parieto-occipital cortex (aSPOC)] in online adjustments of reach-to-grasp coordination to mechanical perturbations (MP) that disrupted arm transport. We used event-related transcranial magnetic stimulation (TMS) to test whether the nodes of these pathways causally contribute to the processing of proprioceptive information when reaching for a virtual visual target at two different perturbation latencies. TMS over aSPOC selectively altered the correction magnitude of arm transport during late perturbations, demonstrating that aSPOC processes proprioceptive inputs related to mechanical perturbations in a movement phase-dependent manner.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11924878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054037","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":"Mapping Eye, Arm, and Reward Information in Frontal Motor Cortices Using Electrocorticography in Nonhuman Primates.","authors":"Tomohiro Ouchi, Leo R Scholl, Pavithra Rajeswaran, Ryan A Canfield, Lydia I Smith, Amy L Orsborn","doi":"10.1523/JNEUROSCI.1536-24.2025","DOIUrl":"10.1523/JNEUROSCI.1536-24.2025","url":null,"abstract":"<p><p>Goal-directed reaches give rise to dynamic neural activity across the brain as we move our eyes and arms and process outcomes. High spatiotemporal resolution mapping of multiple cortical areas will improve our understanding of how these neural computations are spatially and temporally distributed across the brain. In this study, we used micro-electrocorticography (µECoG) recordings in two male monkeys performing visually guided reaches to map information related to eye movements, arm movements, and receiving rewards over primary motor cortex, premotor cortex, frontal eye field, and dorsolateral prefrontal cortex. Time-frequency and decoding analyses revealed that eye and arm movement information shifts across brain regions during a reach, likely reflecting shifts from planning to execution. Although eye and arm movement temporally overlapped, phase clustering analyses enabled us to resolve differences in eye and arm information across brain regions. This analysis revealed that eye and arm information spatially overlapped in motor cortex, which we further confirmed by demonstrating that arm movement decoding performance from motor cortex activity was impacted by task-irrelevant eye movements. Phase clustering analyses also identified reward-related activity in the prefrontal and premotor cortex. Our results demonstrate µECoG's strengths for functional mapping and provide further detail on the spatial distribution of eye, arm, and reward information processing distributed across frontal cortices during reaching. These insights advance our understanding of the overlapping neural computations underlying coordinated movements and reveal opportunities to leverage these signals to enhance future brain-computer interfaces.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11924994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076205","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":"Dynamics of Pitch Perception in the Auditory Cortex.","authors":"Ellie Bean Abrams, Alec Marantz, Isaac Krementsov, Laura Gwilliams","doi":"10.1523/JNEUROSCI.1111-24.2025","DOIUrl":"10.1523/JNEUROSCI.1111-24.2025","url":null,"abstract":"<p><p>The ability to perceive pitch allows human listeners to experience music, recognize the identity and emotion conveyed by conversational partners, and make sense of their auditory environment. A pitch percept is formed by weighting different acoustic cues (e.g., signal fundamental frequency and interharmonic spacing) and contextual cues (expectation). How and when such cues are neurally encoded and integrated remains debated. In this study, 28 participants (16 female) listened to tone sequences with different acoustic cues (pure tones, complex missing fundamental tones, and tones with an ambiguous mixture), placed in predictable and less predictable sequences, while magnetoencephalography was recorded. Decoding analyses revealed that pitch was encoded in neural responses to all three tone types in the low-to-mid auditory cortex and sensorimotor cortex bilaterally, with right-hemisphere dominance. The pattern of activity generalized across cue types, offset in time: pitch was neurally encoded earlier for harmonic tones (∼85 ms) than pure tones (∼95 ms). For ambiguous tones, pitch emerged significantly earlier in predictable contexts than in unpredictable. The results suggest that a unified neural representation of pitch emerges by integrating independent pitch cues and that context alters the dynamics of pitch generation when acoustic cues are ambiguous.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11924889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257323","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":"Transient Upregulation of Procaspase-3 during Oligodendrocyte Fate Decisions.","authors":"Yasmine Kamen, Timothy W Chapman, Enrique T Piedra, Matthew E Ciolkowski, Robert A Hill","doi":"10.1523/JNEUROSCI.2066-24.2025","DOIUrl":"10.1523/JNEUROSCI.2066-24.2025","url":null,"abstract":"<p><p>Oligodendrocytes are generated throughout life and in neurodegenerative conditions from brain resident oligodendrocyte precursor cells (OPCs). The transition from OPC to oligodendrocyte involves a complex cascade of molecular and morphological states that position the cell to make a fate decision to integrate as a myelinating oligodendrocyte or die through apoptosis. Oligodendrocyte maturation impacts the cell death mechanisms that occur in degenerative conditions, but it is unclear if and how the cell death machinery changes as OPCs transition into oligodendrocytes. Here, we discovered that differentiating oligodendrocytes transiently upregulate the zymogen procaspase-3 in both female and male mice, equipping these cells to make a survival decision during differentiation. Pharmacological inhibition of caspase-3 decreases oligodendrocyte density, indicating that procaspase-3 upregulation is linked to successful oligodendrocyte generation. Moreover, using procaspase-3 as a marker, we show that oligodendrocyte differentiation continues in the aging cortex and white matter. Taken together, our data establish procaspase-3 as a differentiating oligodendrocyte marker and provide insight into the underlying mechanisms occurring during the decision to integrate or die.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11924999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015321","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}