Journal of neurophysiology最新文献

{"title":"Acute diffuse axonal injury following repeated mild traumatic brain injury in juvenile rats.","authors":"Erin McDonagh, Eric Eyolfson, Justin Brand, Sandy R Shultz, Brian R Christie","doi":"10.1152/jn.00482.2024","DOIUrl":"10.1152/jn.00482.2024","url":null,"abstract":"<p><p>Mild traumatic brain injuries (mTBIs) are caused by biomechanical forces being transmitted to the brain, causing neuronal connections to be subjected to sheering forces. The injury severity can be affected by a number of factors that include age and sex, however, there remains a paucity of data on how repeated mTBI (r-mTBI) impacts the female brain. In these studies, male and female juvenile rats [<i>postnatal day</i> (PND) <i>25</i>-<i>26</i>] were administered a total of eight mTBIs over a 2-day period. Following each mTBI, rats were immediately assessed for acute neurological impairment. After eight mTBIs were completed, the Barnes maze was used to assess spatial learning and memory. Axonal injury was assessed using silver stain histological analyses. We found that injured females exhibited less acute neurological impairment than males. Three days after the final r-mTBI, no significant differences were observed in spatial learning and memory, with all animals showing similar times to locate the escape platform on the reversal trial, additionally there was no main effect of sex in the Barnes maze. Silver stain uptake was significantly increased in the optic tract, corpus callosum, and cortex compared with sham animals at seven days postinjury in a sex-specific manner. Females showed significant increase in all three regions following r-mTBI, whereas males only showed a significant increase in staining in the optic tract. Overall, these findings show that females may be more susceptible to axonal damage than males, and that cognitive deficits were not evident in this population following r-mTBI. These results indicate that there may be benefits in examining biomarkers that reflect axonal injury and the therapies that target reducing axonal degradation.<b>NEW & NOTEWORTHY</b> Diffuse axonal injury is a hallmark feature of all severities of traumatic brain injury (TBI) yet, in preclinical mild (m)TBI research no studies have yet investigated axonal damage with silver stain immunohistochemistry in female animals. This is a critical gap in the literature as recent studies suggest that females experience mTBI more frequently than males. We found that repeated mTBI (r-mTBI) caused significant diffuse axonal injury that was more pronounced in females compared with males.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"881-891"},"PeriodicalIF":2.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382384","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}

{"title":"Effects of acute intermittent hypoxia on fatigue resistance and voluntary activation of leg muscles in intact humans.","authors":"Aravind Nehrujee, W Zev Rymer, Milap S Sandhu","doi":"10.1152/jn.00026.2025","DOIUrl":"10.1152/jn.00026.2025","url":null,"abstract":"","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"763-764"},"PeriodicalIF":2.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189337","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}

{"title":"Horizontal, vertical, and torsional optokinetic responses and their adaptations in fish.","authors":"Shin Tadokoro, Shuntaro Miki, Toshimi Yamanaka, Yutaka Hirata","doi":"10.1152/jn.00565.2024","DOIUrl":"10.1152/jn.00565.2024","url":null,"abstract":"<p><p>Eye movements in vertebrates moving around stabilize retinal images, achieved through the vestibuloocular reflex (VOR) and the optokinetic response (OKR). Although VOR compensates for head velocity, its effectiveness declines with prolonged motion, necessitating the OKR. This study explores the three-dimensional (3-D) nature of the OKR in goldfish, focusing on horizontal (H), vertical (V), and torsional (T) responses and their adaptation. We found that naïve goldfish exhibited minimal V and TOKR unlike robust HOKR having low-pass characteristics. Through visual training, V and TOKR manifested with flatter frequency spectra, although TOKR toward intorsion unchanged. Memory retention revealed a slower decay of adapted TOKR compared with others. These are the first evaluation of V and TOKR in fish, demonstrating that while naïve goldfish do not rely on V and TOKR in their natural behavior, they retain adaptative capabilities. Vertical and torsional ocular ranges, measured through tilt VOR, well exceeded OKR movement ranges, indicating that minimal VOKR and TOKR are not due to ocular muscle limitations but inherent OKR properties. Head motion analysis in freely swimming goldfish and carp, a closely related species, revealed small, flat frequency spectra in roll and pitch, and large low-pass spectra in yaw in the former, and a significant pitch-down bias during foraging in the latter. These findings suggest that goldfish OKRs are adaptable across axes, reflecting the unique vestibular and visual experiences associated with goldfish locomotor behavior patterns. Notably, the asymmetrical adaptability of TOKR potentially linked to foraging behaviors.<b>NEW & NOTEWORTHY</b> This study provides the first comprehensive evaluation of vertical (V) and torsional (T) optokinetic responses (OKR) in fish, demonstrating that naïve animals exhibit minimal V and TOKR compared with robust horizontal (H) OKR. Visual training revealed adaptive capabilities, with V and TOKR gains increasing, although TOKR showed directional asymmetry. Notably, adapted TOKR exhibited slower memory decay than H and VOKR. These findings highlight the plasticity of OKR and its functional relevance to locomotor behaviors.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"965-986"},"PeriodicalIF":2.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416725","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}

{"title":"Adaptive changes in balance control strategies under continuous exposure to visual-somatosensory conflicts.","authors":"An-Ke Hua, Jing-Yuan Bai, Guo-Zheng Wang, Zeng-Ming Hao, Jun Meng, Jian Wang","doi":"10.1152/jn.00350.2024","DOIUrl":"10.1152/jn.00350.2024","url":null,"abstract":"<p><p>Human postural control system has the capacity to adapt to balance-challenging perturbations. However, the characteristics and mechanisms of postural adaptation to continuous perturbation under the sensory conflicting environments remain unclear. We aimed to investigate the functional role of oscillatory coupling drive to lower-limb muscles with changes in balance control during postural adaptation under multisensory congruent and incongruent environments. We combined a platform moving sinusoidally (0.24 Hz) along the anterior-posterior (AP) axis and a virtual scene moving sinusoidally (0.24 Hz) either along the AP or the medio-lateral (ML) axis to present a 3-min visual-somatosensory congruent condition (<i>n</i> = 10) or incongruent condition (<i>n</i> = 12), respectively. We analyzed the kinematic data and performed intermuscular coherence analysis of surface EMG data from bilateral lower limbs. We found that the inter-limb coherence was larger under the congruent condition and decreased over the 3-min perturbation, while inter-limb coherence remained low and showed no changes under the incongruent condition over the 3-min perturbation. These results suggest that exposure to the incongruent condition disrupted inter-limb intermuscular coupling. Besides, we found the bilateral intra-limb coherence decreased over 3-min congruent and incongruent perturbation, with the bilateral ankle joint angular velocity decreased and the coupling strength (0.2-0.3 Hz) between whole body sway and sinusoidal stimuli in AP decreased. These findings suggest that continuous exposure to sinusoidal perturbation in AP under congruent and incongruent conditions decreased bilateral intermuscular coupling, contributing to flexibility in the sagittal plane. Overall, we suggested the postural control system adapts context specifically to different sensory environments, with distinct characteristics of neuromuscular control strategies.<b>NEW & NOTEWORTHY</b> Lower limb muscle coordination plays a vital role when facing continuous perturbation by updating sensorimotor mappings. However, it is unclear how muscle coordination adapts to visual-somatosensory congruent and incongruent perturbations. Here, we found that muscle coordination showed context-specific adaptive changes to visual-somatosensory congruent or incongruent environment.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"765-774"},"PeriodicalIF":2.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047045","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}

{"title":"Distinct functional roles of narrow and broadband high-gamma activities in human primary somatosensory cortex.","authors":"Seokyun Ryun, Seokbeen Lim, Dong Pyo Jang, Chun Kee Chung","doi":"10.1152/jn.00159.2024","DOIUrl":"10.1152/jn.00159.2024","url":null,"abstract":"<p><p>Previous studies have shown that high-gamma (HG) activity in the primary visual cortex (V1) has distinct higher (broadband) and lower (narrowband) components with different functions and origins. However, it is unclear whether similar segregation exists in the primary somatosensory cortex (S1), and the origins and roles of HG activity in S1 remain unknown. Here, we investigate functional roles and origins of HG activity in S1 during tactile stimulation in humans and a rat model. In the human experiment, lower-frequency HG (50-70 Hz, LHG) was more sensitive to sustained tactile intensity compared with higher-frequency HG (70-150 Hz, HHG). HHG activity varied depending on the ratio of low and high mechanical frequencies, with its pattern reflecting a mixture of neural activities corresponding to them. Furthermore, classification analysis revealed that HHG activity contains more information about texture surfaces compared with LHG activity. In the rat experiment, we found that both HHG and LHG activities are strongest in the somatosensory input layer (layer IV), similar to findings in V1. Interestingly, spike-triggered local field potential (stLFP) analysis revealed significant HG oscillations exclusively in layer IV, indicating a dominant coupling between neuronal firing and HG oscillations in this layer. In summary, HHG activity is associated with detecting changes in the rate of contact force and subtle skin deformations whereas LHG activity reflects the absolute amount of applied contact force. Finally, both HHG and LHG originated in layer IV of S1.<b>NEW & NOTEWORTHY</b> We investigated the functional roles and origins of high-gamma (HG) activity in the primary somatosensory cortex (S1). The higher-frequency component of HG activity is associated with detecting changes in the rate of contact force and subtle skin deformations whereas the lower-frequency component reflects the absolute magnitude of the applied contact force. Both types of HG activity were found to originate in layer IV of S1.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"839-852"},"PeriodicalIF":2.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047050","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}

{"title":"Cortical acetylcholine response to deep brain stimulation of the basal forebrain in mice.","authors":"Khadijah Shanazz, Kun Xie, Tucker Oliver, Jamal Bogan, Fernando L Vale, Jeremy Sword, Sergei A Kirov, Alvin Terry, Philip O'Herron, David T Blake","doi":"10.1152/jn.00476.2024","DOIUrl":"10.1152/jn.00476.2024","url":null,"abstract":"<p><p>Deep brain stimulation (DBS) using electrical stimulation of neuronal tissue in the basal forebrain to enhance release of the neurotransmitter acetylcholine is under consideration to improve executive function in patients with dementia. Although some small studies indicate a positive response in the clinical setting, the relationship between DBS and acetylcholine pharmacokinetics is incompletely understood. We examined the cortical acetylcholine response to different stimulation parameters of the basal forebrain. Two-photon in vivo imaging was combined with deep brain stimulation in C57BL/6J mice. Stimulating electrodes were implanted in the subpallidal basal forebrain, and the ipsilateral somatosensory cortex was imaged. Acetylcholine activity was determined using the GRAB_ACh-3.0 acetylcholine receptor sensor, and blood vessels were visualized with Texas red. Experiments manipulating stimulation frequency demonstrated that integrated acetylcholine-induced fluorescence was insensitive to frequency with the same number of pulses, and that maximum peak levels were achieved with frequencies from 60 to 130 Hz. Altering pulse train length indicated that longer stimulation resulted in higher peaks and more activation with sublinear summation. The acetylcholinesterase inhibitor, donepezil, increased the peak response to 600 pulses of stimulation at 60 Hz, and the integrated response increased by 57% with the 2 mg/kg dose and 126% with the 4 mg/kg dose. Acetylcholine levels returned to baseline with a time constant of 14-18 s. Donepezil increases total acetylcholine receptor activation associated with DBS but does not change temporal kinetics. The long time constants observed in the cerebral cortex add to the evidence supporting volume and synaptic neurotransmission.<b>NEW & NOTEWORTHY</b> Peak acetylcholine responses to deep brain stimulation of the subpallidal basal forebrain increases with increased frequency and number of pulses. Long recovery periods in the 10s of seconds support \"volume\" versus \"phasic\" transmission of acetylcholine. Donepezil administration enhances the effect of stimulation on cortical acetylcholine release.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"825-838"},"PeriodicalIF":2.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006961","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}

{"title":"Neuroimaging meets neurophysiology: vascular endothelial growth factor and regional cerebral blood flow in early Alzheimer's disease.","authors":"Bing Xin Song, Guocheng Jiang, Melissa Wong, Damien Gallagher, Bradley J MacIntosh, Ana C Andreazza, Erika L Beroncal, Sandra E Black, Nathan Herrmann, Jocelyn Charles, Fuqiang Gao, Alex Kiss, Giovanni Marotta, Krista L Lanctôt","doi":"10.1152/jn.00604.2024","DOIUrl":"10.1152/jn.00604.2024","url":null,"abstract":"<p><p>Angiogenesis may play an important role in the pathophysiology of Alzheimer's disease (AD). Previous in vitro and in vivo studies suggest a link between angiogenesis and cerebral blood flow (CBF) in AD; however, this has never been studied clinically. In this sample of study participants with early AD (<i>n</i> = 15), serum vascular endothelial growth factor (VEGF), an angiogenesis biomarker, was negatively associated with regional CBF (rCBF) in the angular gyrus even after bootstrapping at a repetition of 5,000 and controlling for age, sex, and diagnosis (β = -0.015, SE = 0.006, <i>P</i> = 0.02, <i>f</i>² = 0.27, <i>P_bootstrapped</i> = 0.049). Sex-stratified subgroup analyses showed a strong negative correlation between rCBF in the angular gyrus and log-VEGF in males (<i>n</i> = 7; <i>r</i> = -0.78, <i>P</i> = 0.04), but not in females (<i>n</i> = 8; <i>r</i> = -0.16, <i>P</i> = 0.7). These results support an association between angiogenesis and CBF in early AD that should be further investigated in longitudinal studies and may have relevance for future therapeutic interventions in AD.<b>NEW & NOTEWORTHY</b> This manuscript supports the findings from previous in vitro and in vivo Alzheimer's disease (AD) studies where angiogenesis was associated with cerebral blood flow (CBF) changes. Using both neuroimaging and neurophysiology measures, this study showed the association between CBF and blood vascular endothelial growth factor (VEGF) in people with early AD, suggesting further investigation into angiogenesis and CBF as potential therapeutic targets for AD.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"924-929"},"PeriodicalIF":2.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416731","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}

{"title":"Hierarchical emergence of opponent coding in auditory belt cortex.","authors":"Jeffrey S Johnson, Mamiko Niwa, Kevin N O'Connor, Brian J Malone, Mitchell L Sutter","doi":"10.1152/jn.00519.2024","DOIUrl":"10.1152/jn.00519.2024","url":null,"abstract":"<p><p>We recorded from neurons in primary auditory cortex (A1) and middle-lateral belt area (ML) while rhesus macaques either discriminated amplitude-modulated noise (AM) from unmodulated noise or passively heard the same stimuli. We used several post hoc pooling models to investigate the ability of auditory cortex to leverage population coding for AM detection. We find that pooled-response AM detection is better in the active condition than the passive condition, and better using rate-based coding than synchrony-based coding. Neurons can be segregated into two classes based on whether they increase (INC) or decrease (DEC) their firing rate in response to increasing modulation depth. In these samples, A1 had relatively fewer DEC neurons (26%) than ML (45%). When responses were pooled without segregating these classes, AM detection using rate-based coding was much better in A1 than in ML, but when pooling only INC neurons, AM detection in ML approached that found in A1. Pooling only DEC neurons resulted in impaired AM detection in both areas. To investigate the role of DEC neurons, we devised two pooling methods that opposed DEC and INC neurons-a direct subtractive method and a two-pool push-pull opponent method. Only the push-pull opponent method resulted in superior AM detection relative to indiscriminate pooling. In the active condition, the opponent method was superior to pooling only INC neurons during the late portion of the response in ML. These results suggest that the increasing prevalence of the DEC response type in ML can be leveraged by appropriate methods to improve AM detection.<b>NEW & NOTEWORTHY</b> We used several post hoc pooling models to investigate the ability of primate auditory cortex to leverage population coding in the detection of amplitude-modulated sounds. When cells are indiscriminately pooled, primary auditory cortex (A1) detects amplitude-modulated sounds better than middle-lateral belt (ML). When cells that decrease firing rate with increasing modulation depth are excluded, or used in a push-pull opponent fashion, detection is similar in the two areas, and macaque behavior can be approximated using reasonably sized pools.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"944-964"},"PeriodicalIF":2.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441123","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}

{"title":"Excellent test-retest reliability of perturbation-evoked cortical responses supports feasibility of the balance N1 as a clinical biomarker.","authors":"Jasmine L Mirdamadi, Alex Poorman, Gaetan Munter, Kendra Jones, Lena H Ting, Michael R Borich, Aiden M Payne","doi":"10.1152/jn.00583.2024","DOIUrl":"10.1152/jn.00583.2024","url":null,"abstract":"<p><p>There is a growing interest in measuring cortical activity during balance control for understanding mechanisms of impaired balance with aging and neurological dysfunction. The most well-characterized electrophysiological signal elicited by a balance disturbance is the perturbation-evoked N1 potential. We previously found associations between the N1 and balance ability, suggesting it may be a potential biomarker of balance health. However, a potential biomarker will be limited by its reliability and clinical feasibility, which has yet to be established. Here, we characterized the reliability of the balance N1 within and between sessions over a 1-wk interval in 10 younger and 14 older adults, and over a 1-year interval in a subset of older adults (<i>n</i> = 12). We extracted N1 amplitude and latency from the Cz electrode using an advanced, computationally intensive approach (64 electrodes, many trials). Test-retest reliability was assessed using the intraclass correlation coefficient (ICC). Internal consistency was quantified by split-half reliability using the Spearman correlation coefficient. N1s varied across individuals, yet within individuals, showed excellent test-retest reliability (ICC > 0.9) and internal reliability (<i>r</i> > 0.9). N1 amplitude reliability generally plateaued within six trials, whereas more trials were needed to reliably measure latency. Similar results were obtained using a minimal approach (three electrodes, simple preprocessing) and at the component level (largest contributing N1 source). The N1's stability, reliability, and feasibility make it well suited for potential use as a clinical biomarker. Characterizing N1 reliability in different populations and contexts will be necessary to enhance our understanding, optimize experimental design, and determine its predictive validity (e.g., falls risk).<b>NEW & NOTEWORTHY</b> Prior studies identified associations between the perturbation-evoked N1 potential and behaviors that predict falls, suggesting its potential as a biomarker of balance. We show excellent test-retest reliability of the N1 over a year in older adults, and that a reliable measurement can be obtained within six trials using simplified methods, demonstrating clinical feasibility. This study also guides the design of more powerful N1 experiments, necessary to identify underlying mechanisms and assess clinical utility.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"987-1001"},"PeriodicalIF":2.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492432","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}

{"title":"Differentiating the contributions of Na⁺/K⁺ pump current and persistent Na⁺ current in simulated voltage-clamp experiments.","authors":"Jessica R Parker, Jan-Marino Ramirez","doi":"10.1152/jn.00060.2024","DOIUrl":"10.1152/jn.00060.2024","url":null,"abstract":"<p><p>The persistent Na⁺ current (I_NaP) is thought to play important roles in many brain regions including the generation of inspiration in the ventral respiratory column (VRC) of mammals. The characterization of the slow inactivation of I_NaP requires long-lasting voltage steps (>1 s), which will increase intracellular Na⁺ and activate the Na⁺/K⁺-ATPase pump current (I_Pump). Thus, I_Pump may contribute to the previously measured slow inactivation of I_NaP and the generation of the inspiratory bursting rhythm. To test this hypothesis, we computationally modeled a respiratory pacemaker neuron that included a noninactivating I_NaP and I_Pump in addition to other basic spike-generating currents. This model produces an inspiration-like bursting rhythm, in which the dynamics of [Na⁺]_i account for burst initiation and termination. We simulated a voltage-clamp experiment measuring the I_NaP inactivation kinetics using our model of noninactivating I_NaP and I_Pump. Consistent with prior measurements in the VRC, we found a sigmoidal inactivation curve and a current that only partially inactivated reaching a minimum inactivation of 0.37. The biexponential time course of inactivation had decay rate constants of 0.45 s and 2.33 s with contributions of 49% and 51%, respectively. The time constant of inactivation was 2.16 s. This decay was caused by the slow growth of I_Pump and the slow hyperpolarization of the Na⁺ reversal potential in response to the growing [Na⁺]_i. We conclude that important biophysical properties previously attributed to the I_NaP may be caused by I_Pump. This has important implications for understanding respiratory rhythmogenesis and other neuronal functions.<b>NEW & NOTEWORTHY</b> The slow inactivation of the persistent Na⁺ current has been implicated in numerous neuronal functions. Our computational approach indicates that voltage-clamp experiments may show a slow inactivation that is actually caused by the Na⁺/K⁺ pump current and a changing Na⁺ reversal potential rather than a slow Na⁺ inactivation process. These results call into question to what extent the slow inactivation of the persistent Na⁺ current is solely important for neuronal functions.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"904-923"},"PeriodicalIF":2.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006962","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}