Journal of Neuroscience最新文献_第10页

Transient Upregulation of Procaspase-3 during Oligodendrocyte Fate Decisions. 在少突胶质细胞命运决定过程中procaspase-3的短暂上调。

IF 4.4 2区医学

Journal of Neuroscience Pub Date : 2025-03-19 DOI: 10.1523/JNEUROSCI.2066-24.2025

Yasmine Kamen, Timothy W Chapman, Enrique T Piedra, Matthew E Ciolkowski, Robert A Hill

{"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":"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.","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}

引用次数: 0

Neurons of the Central Nucleus of the Amygdala That Express Angiotensin Type 2 Receptors Couple Lowered Blood Pressure with Anxiolysis in Male Mice.

IF 4.4 2区医学

Journal of Neuroscience Pub Date : 2025-03-19 DOI: 10.1523/JNEUROSCI.1482-24.2025

Khalid Elsaafien, Matthew K Kirchner, Karen A Scott, Eliot A Spector, Francesca E Mowry, Colin Sumners, Javier E Stern, Annette D de Kloet, Eric G Krause

{"title":"Neurons of the Central Nucleus of the Amygdala That Express Angiotensin Type 2 Receptors Couple Lowered Blood Pressure with Anxiolysis in Male Mice.","authors":"Khalid Elsaafien, Matthew K Kirchner, Karen A Scott, Eliot A Spector, Francesca E Mowry, Colin Sumners, Javier E Stern, Annette D de Kloet, Eric G Krause","doi":"10.1523/JNEUROSCI.1482-24.2025","DOIUrl":"10.1523/JNEUROSCI.1482-24.2025","url":null,"abstract":"Relief from psychological stress confers cardio-protection by altering brain activity and lowering blood pressure; however, the neuronal circuits orchestrating these effects are unknown. Here, we used male mice to discern neuronal circuits conferring stress relief and reduced blood pressure. We found that neurons residing in the central nucleus of the amygdala (CeA) expressing angiotensin type 2 receptors (AT2R), deemed CeAAT2R, innervate brain nuclei regulating stress responding. In vivo optogenetic excitation of CeAAT2R lowered blood pressure, and this effect was abrogated by systemic hexamethonium or antagonism of GABA receptors within the CeA. Intriguingly, in vivo optogenetic excitation of CeAAT2R was also potently anxiolytic. Delivery of an AT2R agonist into the CeA recapitulated the hypotensive and anxiolytic effects, but ablating AT2R(s) from the CeA was anxiogenic. The results suggest that the excitation of CeAAT2R couples lowered blood pressure with anxiolysis. The implication is that therapeutics targeting CeAAT2R may provide stress relief and protection against cardiovascular disease.","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/PMC11924993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256151","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}

引用次数: 0

The Representation of Stimulus Features during Stable Fixation and Active Vision.

IF 4.4 2区医学

Journal of Neuroscience Pub Date : 2025-03-19 DOI: 10.1523/JNEUROSCI.1652-24.2024

Caoimhe Moran, Philippa A Johnson, Hinze Hogendoorn, Ayelet N Landau

{"title":"The Representation of Stimulus Features during Stable Fixation and Active Vision.","authors":"Caoimhe Moran, Philippa A Johnson, Hinze Hogendoorn, Ayelet N Landau","doi":"10.1523/JNEUROSCI.1652-24.2024","DOIUrl":"10.1523/JNEUROSCI.1652-24.2024","url":null,"abstract":"Predictive updating of an object's spatial coordinates from presaccade to postsaccade contributes to stable visual perception. Whether object features are predictively remapped remains contested. We set out to characterize the spatiotemporal dynamics of feature processing during stable fixation and active vision. To do so, we applied multivariate decoding methods to EEG data collected while human participants (male and female) viewed brief visual stimuli. Stimuli appeared at different locations across the visual field at either high or low spatial frequency (SF). During fixation, classifiers were trained to decode SF presented at one parafoveal location and cross-tested on SF from either the same, adjacent, or more peripheral locations. When training and testing on the same location, SF was classified shortly after stimulus onset (∼79 ms). Decoding of SF at locations farther from the trained location emerged later (∼144-295 ms), with decoding latency modulated by eccentricity. This analysis provides a detailed time course for the spread of feature information across the visual field. Next, we investigated how active vision impacts the emergence of SF information. In the presence of a saccade, the decoding time of peripheral SF at parafoveal locations was earlier, indicating predictive anticipation of SF due to the saccade. Crucially, however, this predictive effect was not limited to the specific remapped location. Rather, peripheral SF was correctly classified, at an accelerated time course, at all parafoveal positions. This indicates spatially coarse, predictive anticipation of stimulus features during active vision, likely enabling a smooth transition on saccade landing.","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/PMC11924989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143068541","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}

引用次数: 0

Kv4.2 Regulates Basal Synaptic Strength by Inhibiting R-Type Calcium Channels in the Hippocampus.

IF 4.4 2区医学

Journal of Neuroscience Pub Date : 2025-03-19 DOI: 10.1523/JNEUROSCI.0444-24.2025

Seung Yeon Lee, Jiwoo Shin, Min Jeong Kwon, Yujin Kim, Won-Kyung Ho, Suk-Ho Lee

{"title":"Kv4.2 Regulates Basal Synaptic Strength by Inhibiting R-Type Calcium Channels in the Hippocampus.","authors":"Seung Yeon Lee, Jiwoo Shin, Min Jeong Kwon, Yujin Kim, Won-Kyung Ho, Suk-Ho Lee","doi":"10.1523/JNEUROSCI.0444-24.2025","DOIUrl":"10.1523/JNEUROSCI.0444-24.2025","url":null,"abstract":"Kv4.2 subunits, which mediate transient A-type K+ current, are crucial in regulating neuronal excitability and synaptic responses within the hippocampus. While their contribution to activity-dependent regulation of synaptic response is well-established, the impact of Kv4.2 on basal synaptic strength remains elusive. To address this gap, we introduced a Kv4.2-specific antibody (anti-Kv4.2) into hippocampal neurons of mice of both sexes to selectively inhibit postsynaptic Kv4.2, enabling direct examination of its impact on excitatory postsynaptic potentials (EPSPs) and currents (EPSCs) during basal synaptic activity. Our results demonstrated that blocking Kv4.2 significantly enhanced the amplitude of EPSPs. This amplification was proportional to the increase in the amplitude of EPSCs, which, in turn, correlated with the expression level of Kv4.2 in the dendritic regions of the hippocampus. Furthermore, the anti-Kv4.2-induced increase in EPSC amplitude was associated with a decrease in the failure rate of EPSCs evoked by minimal stimulation, suggesting that blocking Kv4.2 facilitates the recruitment of AMPA receptors to both silent and functional synapses to enhance synaptic efficacy. The anti-Kv4.2-induced synaptic potentiation was effectively abolished by intracellular 10 mM BAPTA or by blocking R-type calcium channels (RTCCs) and downstream signaling molecules, including protein kinases A and C. Importantly, Kv4.2 inhibition did not occlude further synaptic potentiation induced by high-frequency stimulation, suggesting that anti-Kv4.2-induced synaptic strengthening involves unique mechanisms that are distinct from long-term potentiation pathways. Taken together, these findings underscore the essential role of Kv4.2 in the regulation of basal synaptic strength, which is mediated by the inhibition of RTCCs.","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/PMC11924881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400508","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}

引用次数: 0

Stimulus-Dependent Expression of Bdnf Is Mediated by ATF2, MYT1L, and EGR1 Transcription Factors.

IF 4.4 2区医学

Journal of Neuroscience Pub Date : 2025-03-19 DOI: 10.1523/JNEUROSCI.0313-24.2025

Eli-Eelika Esvald, Andra Moistus, Karin Lehe, Annela Avarlaid, Anastassia Šubina, Liis Kuusemets, Jürgen Tuvikene, Tõnis Timmusk

{"title":"Stimulus-Dependent Expression of Bdnf Is Mediated by ATF2, MYT1L, and EGR1 Transcription Factors.","authors":"Eli-Eelika Esvald, Andra Moistus, Karin Lehe, Annela Avarlaid, Anastassia Šubina, Liis Kuusemets, Jürgen Tuvikene, Tõnis Timmusk","doi":"10.1523/JNEUROSCI.0313-24.2025","DOIUrl":"10.1523/JNEUROSCI.0313-24.2025","url":null,"abstract":"Neurotrophins like BDNF have a key role in the proper functioning of the central nervous system, influencing numerous processes like memory formation and behavior. An imbalance in BDNF levels can lead to a wide range of diseases, including depression and neurodevelopmental disorders. While the potential therapeutic effects of BDNF are well-recognized, there is a knowledge gap in understanding the mechanisms governing BDNF expression levels. Here, we focused on the regulation of Bdnf gene expression in response to different stimuli, specifically studying the effects of neuronal activity and BDNF-TrkB signaling on Bdnf transcription in cultured neurons from rats of either sex. We used in vitro DNA pulldown combined with mass spectrometry to determine transcription factors that interact with the Bdnf promoters upon different stimuli and validated numerous known regulators, such as USF and AP1 family, and novel candidate regulators using reporter assays. We show that the USF family of transcription factors is specifically recruited after membrane depolarization, whereas the AP1 family participates in Bdnf regulation only after BDNF-TrkB signaling. We further describe ATF2, MYT1L, and EGR family as novel regulators of Bdnf expression by demonstrating their direct binding to Bdnf promoters using chromatin immunoprecipitation assays both in vitro and in vivo, showing their functional role in Bdnf gene expression and ultimately identifying their regulatory cis-elements in Bdnf promoters. Furthermore, our results show competition between ATF2, CREB, and AP1 family in regulating Bdnf levels. Collectively, our results provide insight into the regulation of Bdnf expression upon different stimuli.","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/PMC11924897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416074","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}

引用次数: 0

From Circuits to Lifespan: Translating Mouse and Human Timelines with Neuroimaging-Based Tractography.

IF 4.4 2区医学

Journal of Neuroscience Pub Date : 2025-03-19 DOI: 10.1523/JNEUROSCI.1429-24.2025

Nicholas C Cottam, Kwadwo Ofori, Kevin T Stoll, Madison Bryant, Jessica R Rogge, Khan Hekmatyar, Jianli Sun, Christine J Charvet

{"title":"From Circuits to Lifespan: Translating Mouse and Human Timelines with Neuroimaging-Based Tractography.","authors":"Nicholas C Cottam, Kwadwo Ofori, Kevin T Stoll, Madison Bryant, Jessica R Rogge, Khan Hekmatyar, Jianli Sun, Christine J Charvet","doi":"10.1523/JNEUROSCI.1429-24.2025","DOIUrl":"10.1523/JNEUROSCI.1429-24.2025","url":null,"abstract":"Animal models are commonly used to investigate developmental processes and disease risk, but humans and model systems (e.g., mice) differ substantially in the pace of development and aging. The timeline of human developmental circuits is well known, but it is unclear how such timelines compare with those in mice. We lack age alignments across the lifespan of mice and humans. Here, we build upon our Translating Time resource, which is a tool that equates corresponding ages during development. We collected 1,125 observations from age-related changes in body, bone, dental, and brain processes to equate corresponding ages across humans, mice, and rats to boost power for comparison across humans and mice. We acquired high-resolution diffusion MR scans of mouse brains (n = 16) of either sex at sequential stages of postnatal development [postnatal day (P)3, 4, 12, 21, 60] to track brain circuit maturation (e.g., olfactory association, transcallosal pathways). We found heterogeneity in white matter pathway growth. Corpus callosum growth largely ceases days after birth, while the olfactory association pathway grows through P60. We found that a P3-4, mouse equates to a human at roughly GW24 and a P60 mouse equates to a human in teenage years. Therefore, white matter pathway maturation is extended in mice as it is in humans, but there are species-specific adaptations. For example, olfactory-related wiring is protracted in mice, which is linked to their reliance on olfaction. Our findings underscore the importance of translational tools to map common and species-specific biological processes from model systems to humans.","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/PMC11925001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054058","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}

引用次数: 0

The Frequency and State-Dependent Relationship between Pupil Size and Respiration.

IF 4.4 2区医学

Journal of Neuroscience Pub Date : 2025-03-19 DOI: 10.1523/JNEUROSCI.2410-24.2025

Deepa Issar

引用次数: 0

Disentangling the Component Processes in Complex Planning Impairments Following Ventromedial Prefrontal Lesions.

IF 4.4 2区医学

Journal of Neuroscience Pub Date : 2025-03-19 DOI: 10.1523/JNEUROSCI.1814-24.2025

Eleanor Holton, Bas van Opheusden, Jan Grohn, Harry Ward, John Grogan, Patricia L Lockwood, Ili Ma, Wei Ji Ma, Sanjay G Manohar

{"title":"Disentangling the Component Processes in Complex Planning Impairments Following Ventromedial Prefrontal Lesions.","authors":"Eleanor Holton, Bas van Opheusden, Jan Grohn, Harry Ward, John Grogan, Patricia L Lockwood, Ili Ma, Wei Ji Ma, Sanjay G Manohar","doi":"10.1523/JNEUROSCI.1814-24.2025","DOIUrl":"10.1523/JNEUROSCI.1814-24.2025","url":null,"abstract":"Damage to the ventromedial prefrontal cortex (vmPFC) in humans disrupts planning abilities in naturalistic settings. However, it is unknown which components of planning are affected in these patients, including selecting the relevant information, simulating future states, or evaluating between these states. To address this question, we leveraged computational paradigms to investigate the role of vmPFC in planning, using the board game task \"Four-in-a-Row\" (18 lesion patients, 9 female; 30 healthy control participants, 16 female) and the simpler \"Two-Step\" task measuring model-based reasoning (49 lesion patients, 27 female; 20 healthy control participants, 13 female). Damage to vmPFC disrupted performance in Four-in-a-Row compared with both control lesion patients and healthy age-matched controls. We leveraged a computational framework to assess different component processes of planning in Four-in-a-Row and found that impairments following vmPFC damage included shallower planning depth and a tendency to overlook game-relevant features. In the \"Two-Step\" task, which involves binary choices across a short future horizon, we found little evidence of planning in all groups and no behavioral differences between groups. Complex yet computationally tractable tasks such as \"Four-in-a-Row\" offer novel opportunities for characterizing neuropsychological planning impairments, which in vmPFC patients we find are associated with oversights and reduced planning depth.","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/PMC11924998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076176","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}

引用次数: 0

Scaling of Ventral Hippocampal Activity during Anxiety.

IF 4.4 2区医学

Journal of Neuroscience Pub Date : 2025-03-19 DOI: 10.1523/JNEUROSCI.1128-24.2025

Carlo Cerquetella, Camille Gontier, Thomas Forro, Jean-Pascal Pfister, Stéphane Ciocchi

{"title":"Scaling of Ventral Hippocampal Activity during Anxiety.","authors":"Carlo Cerquetella, Camille Gontier, Thomas Forro, Jean-Pascal Pfister, Stéphane Ciocchi","doi":"10.1523/JNEUROSCI.1128-24.2025","DOIUrl":"10.1523/JNEUROSCI.1128-24.2025","url":null,"abstract":"The hippocampus supports a multiplicity of functions, with the dorsal region contributing to spatial representations and memory and the ventral hippocampus (vH) being primarily involved in emotional processing. While spatial encoding has been extensively investigated, how the vH activity is tuned to emotional states, e.g., to different anxiety levels, is not well understood. We developed an adjustable linear track maze for male mice with which we could induce a scaling of behavioral anxiety levels within the same spatial environment. Using in vivo single-unit recordings, optogenetic manipulations, and population-level analysis, we examined the changes and causal effects of vH activity at different anxiety levels. We found that anxiogenic experiences activated the vH and that this activity scaled with increasing anxiety levels. We identified two processes that contributed to this scaling of anxiety-related activity: increased tuning and successive remapping of neurons to the anxiogenic compartment. Moreover, optogenetic inhibition of the vH reduced anxiety across different levels, while anxiety-related activity scaling could be decoded using a linear classifier. Collectively, our findings position the vH as a critical limbic region that functions as an \"anxiometer\" by scaling its activity based on perceived anxiety levels. Our discoveries go beyond the traditional theory of cognitive maps in the hippocampus underlying spatial navigation and memory, by identifying hippocampal mechanisms selectively regulating anxiety.","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/PMC11924894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054041","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}

引用次数: 0

K_V1 Channels Enable Myelinated Axons to Transmit Spikes Reliably without Spiking Ectopically.

IF 4.4 2区医学

Journal of Neuroscience Pub Date : 2025-03-19 DOI: 10.1523/JNEUROSCI.1889-24.2025

Nooshin Abdollahi, Yu-Feng Xie, Stéphanie Ratté, Steven A Prescott

{"title":"KV1 Channels Enable Myelinated Axons to Transmit Spikes Reliably without Spiking Ectopically.","authors":"Nooshin Abdollahi, Yu-Feng Xie, Stéphanie Ratté, Steven A Prescott","doi":"10.1523/JNEUROSCI.1889-24.2025","DOIUrl":"10.1523/JNEUROSCI.1889-24.2025","url":null,"abstract":"Action potentials (spikes) are regenerated at each node of Ranvier during saltatory transmission along a myelinated axon. The high density of voltage-gated sodium channels required by nodes to reliably transmit spikes increases the risk of ectopic spike generation in the axon. Here we show that ectopic spiking is avoided because KV1 channels prevent nodes from responding to slow depolarization; instead, axons respond selectively to rapid depolarization because KV1 channels implement a high-pass filter. To characterize this filter, we compared spike initiation properties in the soma and axon of CA1 pyramidal neurons from mice of both sexes, using spatially restricted photoactivation of channelrhodopsin-2 (ChR2) to evoke spikes in either region while simultaneously recording at the soma. Somatic photostimulation evoked repetitive spiking whereas axonal photostimulation evoked transient spiking. Blocking KV1 channels converted the axon photostimulation response to repetitive spiking and encouraged spontaneous ectopic spike initiation in the axon. According to computational modeling, the high-pass filter implemented by KV1 channels matches the axial current waveform associated with saltatory conduction, enabling axons to faithfully transmit digital signals by maximizing their signal-to-noise ratio for this task. Specifically, a node generates a single spike only when rapidly depolarized, which is precisely what occurs during saltatory conduction when a pulse of axial current (triggered by a spike occurring at the upstream node) reaches the next node. The soma and axon use distinct spike initiation mechanisms (filters) appropriate for the task required of each region, namely, analog-to-digital transduction in the soma versus digital signal transmission in the axon.","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/PMC11924992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069373","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}

引用次数: 0