Journal of neurophysiology最新文献

{"title":"Serotonin selectively modulates visual responses of object motion detectors in <i>Drosophila</i>.","authors":"David J Bertsch, Lesly M Palacios Castillo, Mark A Frye","doi":"10.1152/jn.00154.2025","DOIUrl":"10.1152/jn.00154.2025","url":null,"abstract":"<p><p>Serotonin (5-HT) is a hormonal messenger that confers state-level changes upon the nervous system in both humans and flies. In <i>Drosophila</i>, lobula columnar (LC) cells are feature-detecting neurons that project from the optic lobe to the central brain, where each population forms an anatomically distinct glomerulus with heterogeneous synaptic partners. Here, we investigated serotonin's effect on two LC populations with different 5-HT receptor expression profiles. Receptor expression does not predict neuromodulatory effects. LC15 expresses inhibitory 5-HT1A and 5-HT1B receptors, yet serotonin increases the amplitude of calcium responses to visual stimuli. LC12 expresses inhibitory 5-HT1A and excitatory 5-HT2A receptors, yet serotonin application does not influence visual responses. Serotonin targets select visual response properties, potentiating LC15 responses to a motion-defined bar and tuning the gain of responses to varying object velocity, but has no influence on contrast sensitivity. Serotonin does not significantly facilitate LC15 responses in postsynaptic dendrites, only in the presynaptic terminals of the glomerulus, which suggests that the neuromodulatory effects are strongest in the central brain. Connectomics confirms that LC12 and LC15 share neither presynaptic inputs nor postsynaptic outputs in the central brain. The wiring diagram shows no synaptic interactions between the LC15 circuit and major serotonergic 5-HTPLP neurons, nor to other serotonergic neurons of the central brain, suggesting that endogenous 5-HT acts via paracrine transmission on nonserotonergic pathways. Lobula- and glomerulus-specific GABAergic and glutamatergic inhibitory partners, positioned to filter visual stimuli, are putative 5-HT targets. These results provide a comparative framework for the neuromodulatory mechanisms involved in visual processing.<b>NEW & NOTEWORTHY</b> How does neuromodulatory state affects visual feature detection? In this work, we demonstrate highly specific facilitated visual responses of object-detecting neurons after serotonin bath application in Drosophila. Serotonin potentiates motion-defined bar responses in object-detecting LC15 neurons and tunes response gain to translating bars of mid-range velocities in presynaptic axon terminals. Our calcium imaging extends what is known about extra-synaptic neuromodulation in the visual system and shows that serotonin heightens visual processes that inform object-specific behavior.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"962-984"},"PeriodicalIF":2.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12431381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144883055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Problem difficulty and expertise modulate planning performance in a virtually embodied task.","authors":"Riccardo Moretti, Jeremy Gordon, Antonella Maselli, Giovanni Pezzulo","doi":"10.1152/jn.00236.2025","DOIUrl":"10.1152/jn.00236.2025","url":null,"abstract":"<p><p>Expertise in cognitively and motorically demanding tasks, such as indoor climbing and bouldering, is often associated with enhanced planning abilities, yet the specific relationship between cognitive and motor planning in such tasks remains underexplored. This study investigates how expertise influences route planning in bouldering, with a focus on the impact of problem difficulty. We asked expert and novice climbers to virtually solve easy and hard bouldering problems on a familiar indoor climbing wall, using a custom app that allowed them to plan and select sequences of hand movements. Our results show that climbers are slower and less accurate in solving problems that are harder to climb, despite sharing the same perceptual features with easier problems, suggesting a link between the motoric difficulty of solving problems and the accuracy of planning them. Furthermore, expert climbers made fewer severe planning errors and solved problems faster than novices, indicating an advantage in planning ability beyond physical climbing skills. Interestingly, novice climbers were more likely to make short-sighted planning errors in easy problems, opting for nearby holds that were not part of the correct sequence. These findings extend our understanding of how expertise modulates the relationship between cognitive and motor planning, highlighting the role of planning depth and strategy in physically constrained environments. The study also suggests that future research should explore the mechanisms supporting route planning, such as embodied simulation, to better understand the cognitive and motor processes underlying expert performance in dynamic, embodied tasks.<b>NEW & NOTEWORTHY</b> This study investigates the way climbing expertise shapes planning across varying problem difficulties. Using a novel virtual route-planning tool, the study reveals that participants are less accurate and slower when planning how to solve hard problems. Furthermore, experts plan more accurately and efficiently and avoid short-sighted errors that novices make with higher frequency. These findings highlight how problem difficulty and expertise influence planning accuracy in virtually embodied environments.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"1058-1067"},"PeriodicalIF":2.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957755","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":"Unlocking new mechanisms for future ALS therapies: early interventions with cholinergic antagonists reduce neuromuscular decline.","authors":"Reynaldo Popoli, Tyler L Wells, Turgay Akay","doi":"10.1152/jn.00306.2025","DOIUrl":"https://doi.org/10.1152/jn.00306.2025","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition characterized by motor neuron loss, leading to muscle paralysis and death. C-boutons have been shown to be part of the compensatory mechanism behind delayed symptom onset, and are most active during vigorous exercises, like swimming. When mutant mice with silenced C-boutons perform this exercise, disease progression and behavioral performance drastically improve. Genetic manipulation of C-boutons in human patients remains limited, therefore, we sought to manipulate these synapses using cholinergic antagonists in the presence and absence of exercise in a mouse model of ALS. We demonstrate that atropine and methoctramine administration yield significant improvements in human endpoints, weight maintenance, treadmill performance, and grip strength. Most remarkably, muscle innervation was greatly enhanced at humane endpoints compared to controls, suggesting these drugs provide a protective effect against loss of motor control. We found that methoctramine provided greater benefits in the absence of exercise, hinting at the presence of novel cholinergic mechanisms that can be manipulated in order to preserve motor function. Moreover, we provide evidence that these results are independent of C-boutons, and that methoctramine does not appear to cross the blood-brain barrier. Our results reveal pharmacological mechanisms by which muscle denervation can be reduced, thereby decreasing the rate of disease progression. We have uncovered a promising avenue for improving ALS symptoms by pharmacologically manipulating cholinergic transmission. This mechanism presents as a possible therapy translatable to the clinical setting, which has the potential to prevent the loss of motor control in patients with ALS.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957768","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":"Experimental and computational analysis of REM sleep distributed cortical activity in mice.","authors":"Mathias Peuvrier, Laura Fernandez, Sylvain Crochet, Alain Destexhe, Paul Salin","doi":"10.1152/jn.00344.2024","DOIUrl":"https://doi.org/10.1152/jn.00344.2024","url":null,"abstract":"<p><p>Although classically Rapid-Eye Movement (REM) sleep was thought to generate desynchronized activity similar to wakefulness, it was found that some brain regions could express Slow Wave activity (SWA), a pattern which was normally typical of slow-wave sleep. To investigate possible underlying mechanisms, we analyzed experimental recordings and introduced a computational model of mice cerebral cortex in REM sleep. We characterized the patterns of slow-wave activity across somatosensory and motor areas, and found that the most prominent REM-related SWA was present in the primary (S1) and secondary (S2) somatosensory areas, more rarely seen in motor cortex, and absent from prefrontal cortex or hippocampus. The SWA also tended to be synchronized in S1 and S2. We next investigated possible mechanisms by using a computational model of the mouse brain consisting of adaptive Exponential (AdEx) mean-fields connected together according to the mouse connectome. To compare with experimental data, the local field potential was calculated in each mouse brain region. To reproduce the experiments, we had to assume a heterogeneous level of adaptation in different cortical regions during REM sleep. In these conditions, the model reproduced some of the experimental observations in the somato-motor areas and the other cortical areas. We then used the model to test how the presence of SWA affected cortical responsiveness. Indeed, we found that the areas expressing SWA had diminished evoked responses, which may have participated in a diminished responsiveness during REM sleep.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957484","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":"Neurostomatology: neologism or a paradigm change? A perspective evaluation.","authors":"Rodrigo Valério, Israel Júnior Borges do Nascimento, Patrícia Valério","doi":"10.1152/jn.00149.2025","DOIUrl":"10.1152/jn.00149.2025","url":null,"abstract":"<p><p>The stomatognathic system (SS) has gained higher visibility over the last decades due to emerging primary records evaluating its complex relationships with the central nervous system (CNS). Multiple anatomical and functional functions can be correlated with the SS, including its critical role in craniofacial development, sensory perception, and motor coordination. Despite its central role in neurosensory integration, its relationship with the central nervous system (CNS) remains underexplored in the neurological sciences. The present study aimed to revisit the major (but commonly unexplored) principles of jaw functional orthopedics (JFO) and evidence emerging academic foundation that supports the reframing of the SS within a generalized taxonomy of neural regulation and plasticity. We assessed whether the suggested terminology \"neurostomatology\" adequately reflects true conceptual scientific advancements or should be considered as a mere neologism. This study used principles of integrative synthesis of the literature, including evidence from multiple fields and medical specialties. Therefore, we collated information related to embryology, neural crest migration, cranial nerve distribution, neurotrophins signaling, bone mechanotransduction, and CNS-SS feedback loops. In addition, we emphasized our analysis and descriptive summarization on experimental and clinical results correlating mastication, neuroplasticity, and hippocampal function. The SS is derived from neural crest cells and is formed by a dense network of afferent and efferent neural pathways and connections, exhibiting a highly developed proprioceptive sensitivity property. The functional stimulation of the SS, especially related to the mastication activation, has been demonstrated to impact hippocampal activity, besides modulating neurotrophins expression and shaping bone architecture through cellular signaling networks. The collated evidence highlights SS as an active modulator of neural development, maintenance, and adaptation. Based on the various publications aforementioned, the authors conclude that the term \"neurostomatology\" is not solely a neologism, but depicts an existing paradigm shift in comprehending of stomatognathic system physiology. This expanded evaluation of literature and historical features related to the theme reinforces the fundamentals of JFO.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"486-492"},"PeriodicalIF":2.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540586","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":"Predicted task success and outcome history mediate eye movements toward locations with high informational or motivational value.","authors":"Theresa K Brand, Alexander C Schütz, Hermann Müller, Heiko Maurer, Mathias Hegele, Lisa K Maurer","doi":"10.1152/jn.00072.2025","DOIUrl":"10.1152/jn.00072.2025","url":null,"abstract":"<p><p>Previous research revealed that the action outcomes of self-generated movements can be predicted internally before outcome feedback becomes available. These sensorimotor predictions have been shown to guide gaze toward locations in the environment with high informational value for feedback processing. To test whether they can further be used to assign specific values to different parts of the visible space in the context of motor learning, we assessed systematic differences between gaze toward targets with high informational value (showing graded movement outcome feedback) and targets with high motivational value (showing the monetary reward in a current trial) as a function of (predicted) task success (hit vs. miss) in a goal-directed throwing task. We observed large interindividual differences in the proportion of fixations on each target, highlighting that stable individual tendencies strongly influence whether gaze is directed toward informational or motivational content. However, individual baseline proportions were fine-tuned by the throwing outcome of previous trials (e.g., a larger proportion of fixations on the informational target in trials that followed a miss in the previous trial) and the predicted outcome of a current trial (a larger proportion of fixations on the motivational target in predicted hits compared to misses). Thus, we conclude that, in the context of motor learning, humans combine outcome history with sensorimotor predictions, including the predictive valuation of outcome feedback, to assign value to different parts of the visible space and to guide gaze at highly valued locations, albeit modestly and subordinate to more stable individual preferences.<b>NEW & NOTEWORTHY</b> We elucidate the potential benefits of internally generated action outcome predictions with respect to the optimization of information uptake in the context of motor learning. Here, we show that outcome predictions are used in combination with outcome history to weigh the value of different parts of the environment, albeit being subordinate to stable individual gaze preferences.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"568-579"},"PeriodicalIF":2.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649744","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":"Tracking the cortical processing pathway of representational contents during emotional conflicts.","authors":"Negin Gholamipourbarogh, Antje Opitz, Roula Jamous, Josua Zimmermann, David Cole, Boris B Quednow, Ann-Kathrin Stock, Christian Beste","doi":"10.1152/jn.00163.2025","DOIUrl":"10.1152/jn.00163.2025","url":null,"abstract":"<p><p>The monitoring of conflicting information, including emotional information, is essential for goal-directed acting. Even though the neurophysiological and functional neuroanatomical underpinnings of these processes have been investigated intensively, what has been examined at the neurophysiological level is still insufficient to explain/better understand the processes postulated as relevant by the cognitive theory of emotional conflicts. This particularly refers to how representations of emotionally conflicting information are handled in possibly different functional neuroanatomical structures and neural activity profiles. We investigated this question with an emotional Stroop task combining various EEG analysis methods in a sample of <i>n</i> = 44 healthy participants. The results revealed robust emotional conflict effects on the behavioral level. The neurophysiological data analysis revealed that distinct functional neuroanatomical structures play specific roles during the processing of representational content during emotional conflict monitoring. Starting in sensory cortices, representational content of emotional conflicts can be tracked through the insular cortex to the inferior and superior parietal cortex and medial frontal cortices. Each of these regions process representational content coded by spatially independent activity profiles. The findings show that emotional conflict monitoring reflects a dynamic interplay of multiple brain regions, each processing specific aspects of task-relevant representations.<b>NEW & NOTEWORTHY</b> Emotional conflict monitoring reflects a dynamic interplay of multiple brain regions, each processing specific aspects of information.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"628-641"},"PeriodicalIF":2.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144707820","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":"Inter-limb and handedness differences in the adaptation to brief movement perturbations.","authors":"Weiwei Zhou, Katelyn Haly, Neena Deshpande, Wilsaan M Joiner","doi":"10.1152/jn.00592.2024","DOIUrl":"10.1152/jn.00592.2024","url":null,"abstract":"<p><p>Handedness or limb preference is a well-known aspect of upper-limb motor control lateralization. However, its impact on motor adaptation remains poorly understood. Here, using brief, force perturbations, we examined how inter-limb and handedness differences influence the online corrective response and adaptation when movement was randomly disrupted. We tested both limbs of human subjects (<i>n</i> = 50, 33 females) who exhibited different hand preferences. The correction to the perturbation (applied early, late, or mid-movement) was similar between limbs, but was significantly different between right- and left-handed individuals, with mixed-handed subjects falling in between. Similar to the corrections, the total force generated during the adaptive response differed significantly between right- and left-handed individuals, and in the majority of cases, mixed-handed subjects again fell between the two. In addition, the single-trial adaptation to the perturbation (i.e., the temporal force profile) was well-characterized by a linear combination of the scaled movement kinematics (i.e., the limb motion states-longitudinal position and velocity). Interestingly, handedness had less influence on how this movement information was integrated in the adaptive response; the dependence of the temporal pattern of force on movement velocity and position changed based on when the perturbation occurred and was significantly modified more for the left limb compared with the right. However, this spatiotemporal modulation was similar for right- and left-handed groups, but distinctly different for mixed-handed subjects. These results demonstrate <i>1</i>) a systematic difference in motor corrections based on handedness and <i>2</i>) inter-limb differences in how spatiotemporal properties influence the integration of motion-state information.<b>NEW & NOTEWORTHY</b> This study characterized performance differences influenced by handedness in upper limb motor control. Correction to movement perturbations changed based on handedness, with mixed-handed subjects showing behavior that was between right- and left-handed individuals. In addition, the motion state dependence of the adaptive response varied between limbs, with the left limb showing more sensitivity to the temporal properties of the perturbation. Our results provide novel insight into how handedness is reflected in the coding of limb motion.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"766-782"},"PeriodicalIF":2.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144707818","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":"Feeding state-specific hormonal tuning of neural circuit modulation.","authors":"Logan J Fickling, Aaron P Cook, Wenxin Wu, Angel Erbey Ibarra, Lingjun Li, Michael P Nusbaum","doi":"10.1152/jn.00164.2025","DOIUrl":"10.1152/jn.00164.2025","url":null,"abstract":"<p><p>Studies of hormone influences on neural circuits and behavior have primarily focused on the manipulation of individual hormones. Here, we examine the influence of behavioral (feeding) state-specific hormonal environments on the gastric mill (chewing) circuit configured by the neuropeptide Gly¹-SIFamide (G-SIFamide) in the isolated <i>Cancer borealis</i> stomatogastric ganglion (STG). The G-SIFamide-activated gastric mill rhythm, which is similar to that driven by the G-SIFamidergic projection neuron modulatory commissural neuron 5 (MCN5), is distinguished from other gastric mill rhythms by the presence of rhythmic, prolonged inferior cardiac (IC) neuron bursts and associated interruptions of the pyloric rhythm. Applying 1 µM G-SIFamide in saline only occasionally activated the gastric mill rhythm, whereas this rhythm occurred more frequently when 1 µM G-SIFamide was applied in hemolymph from an unfed crab and even more often in 1-h postfed hemolymph. No novel gastric mill neuron activity occurred under these latter conditions, suggesting that hemolymph strengthened the G-SIFamide actions. Supporting this suggestion, 10 µM G-SIFamide in saline elicited this rhythm as frequently as 1 µM G-SIFamide in unfed hemolymph. Moreover, any G-SIFamide application following an initial application of 1 µM G-SIFamide in hemolymph (unfed or fed) or 10 µM G-SIFamide in saline, but not 1 µM G-SIFamide in saline, activated the gastric mill rhythm less frequently. Mass spectrometry analysis indicated that the hemolymph influence was unlikely due to additional G-SIFamide, because no SIFamide peptide family members were identified in either hemolymph. These results suggest that one or more non-SIFamide hormones strengthen this neuropeptide-modulated circuit output by increasing the effectiveness of the applied G-SIFamide.<b>NEW & NOTEWORTHY</b> We establish that a complete, natural hormonal environment (hemolymph) increases the likelihood of a neuropeptide activating the gastric mill (chewing) rhythm in the crab stomatogastric ganglion (STG). The similar action of a higher neuropeptide concentration in saline, its comparable desensitizing effect to that of neuropeptide plus hemolymph on subsequent neuropeptide applications, and the absence of that neuropeptide in hemolymph suggest one or more distinct hormones act to enhance the effectiveness of the applied peptide.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"642-666"},"PeriodicalIF":2.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12450063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144637313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of persistent inward currents in alpha motoneurons with joint angle depends on muscle length.","authors":"Valentin Goreau, Quentin Morvan, François Hug, Guillaume Le Sant, Raphaël Gross, Thomas Cattagni","doi":"10.1152/jn.00097.2025","DOIUrl":"10.1152/jn.00097.2025","url":null,"abstract":"<p><p>During voluntary movement, activity of alpha motoneurons is modulated to account for changes in muscle force-generating capacity induced by variations in muscle length. To date, research has primarily focused on the modulation of ionotropic inputs, whereas the role of another key contributor to alpha motoneuron activity, persistent inward currents (PICs), has been largely overlooked. In this human study involving young male participants (<i>n</i> = 19), high-density surface electromyography signals were recorded from the gastrocnemius medialis and soleus muscles at different ankle positions, and subsequently decomposed into motor unit spiking activity. Metrics extracted from these spiking activities were used to estimate the respective contributions of PICs, neuromodulation, and inhibition to alpha motoneurons' activity. To differentiate the impact of muscle length from muscle tension, we compared voluntary contractions performed at both similar relative torque levels and similar absolute torque levels across different ankle positions. Our results revealed that PIC-induced prolongation of motor unit discharges was reduced at longer muscle lengths, accompanied by increased inhibition. This effect was consistent across both relative and absolute torque conditions, supporting the hypothesis that muscle length is the primary driver of PICs modulation with change of position. These findings suggest that PICs may serve as an additional mechanism-likely related to inhibitory inputs-to regulate alpha motoneuron activity, ensuring adaptation to changes in muscle length.<b>NEW & NOTEWORTHY</b> Little is known about how motoneuron activity is regulated to generate muscle contractions that adapt to variations in the muscle's force-generating capacity resulting from changes in muscle length. In this human study, we observed that the prolongation of discharge induced by persistent inward currents is modulated by muscle length, likely through the regulation of inhibitory inputs. Alongside the modulation of ionotropic inputs, this may serve as a regulatory mechanism to account for variations in muscle length.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"493-503"},"PeriodicalIF":2.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540585","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}