Journal of neurophysiology最新文献

{"title":"An EEG-based evaluation of antidepressant effects of ketamine enantiomers and metabolites in monkeys.","authors":"North Pinkley","doi":"10.1152/jn.00204.2026","DOIUrl":"10.1152/jn.00204.2026","url":null,"abstract":"<p><p>Ketamine has shown promise as a rapid-acting antidepressant, but its mechanisms of action and optimal formulation remain incompletely understood. Iwamura et al. (<i>J Neurophysiol</i> 135: 935-950, 2026) used electroencephalography (EEG), a measure of brain electrical activity, to compare how ketamine enantiomers and metabolites differ in their effects on brain activity in a primate model. This mini-review summarizes their findings and examines how this work may inform future research and advance understanding of ketamine-based treatments for depression.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"1344-1347"},"PeriodicalIF":2.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148829388","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":"Estimates of tibialis anterior persistent inward current are reduced by heel pressure in a supine position.","authors":"Ryan W Weller, Tushar Sharma, Leah R Bent, Jayne M Kalmar","doi":"10.1152/jn.00570.2025","DOIUrl":"10.1152/jn.00570.2025","url":null,"abstract":"<p><p>Persistent inward currents (PICs) amplify and sustain motor neuron (MN) output. PICs rely on descending monoaminergic input and are reduced by afferent inhibition. Because PICs are thought to be important for postural maintenance, and there is coupling between plantar cutaneous sensory input and lower limb MNs, our purpose was to assess posture-dependent plantar cutaneous sensory modulation of tibialis anterior (TA) MNs. We hypothesized that cutaneous input, via either heel pressure (HP) or electrical stimulation (Stim), would decrease ΔF estimates of PICs derived from paired motor unit recordings, and that ΔF would be lower in a supine posture. Twenty participants (10 females) performed isometric dorsiflexion contractions with (HP) and without (noHP) heel pressure in seated (SE) and supine (SUP) postures. Cutaneous stimulation (5 × 1 ms pulses, 333 Hz, 2x perceptual threshold) was applied to the heel during half the contractions. ΔF was lower with HP (3.77 ± 1.65 Hz) than noHP (4.87 ± 1.25 Hz), but only in SUP (<i>P</i> = 0.027). ΔF in the seated posture was not different between HP (4.28 ± 1.29 Hz) and noHP (4.46 ± 1.59 Hz) conditions. However, ΔF values were not altered by electrical stimulation (Stim: 4.25 ± 1.44 Hz, no Stim: 4.45 ± 1.55 Hz). This suggests that plantar cutaneous pressure shapes MN excitability via modulation of PICs in a posture-dependent manner. This study adds to our understanding of reflex control of lower limb PICs in tasks associated with plantar cutaneous pressures, such as locomotion or postural stability, where task performance depends upon MN input-output properties.<b>NEW & NOTEWORTHY</b> Our study demonstrates that estimates of PIC are modulated by plantar cutaneous input via mechanical pressure, but not via electrical stimulation, and that this cutaneous sensory modulation is posture-dependent.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"1305-1320"},"PeriodicalIF":2.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794326","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":"Cerebral vestibular-evoked potentials depend on body orientation.","authors":"Paul Kobliska, Lou Seropian, Yannick Becker, Yves Cazals, Christophe Lopez","doi":"10.1152/jn.00116.2026","DOIUrl":"10.1152/jn.00116.2026","url":null,"abstract":"<p><p>Otolithic vestibular receptors encode linear acceleration and head orientation relative to gravity, providing a fundamental reference signal for perception, action, and higher-order cognitive functions. However, the cerebral dynamics of otolithic information processing and their sensitivity to body orientation remain poorly characterized. Here, we used sound-induced vestibular stimulation combined with electroencephalography (EEG) in human participants to characterize vestibular-evoked potentials (vEPs) and to examine how body orientation relative to gravity modulates these responses. Otolithic activation was validated using cervical vestibular-evoked myogenic potentials, confirming activation of otolithic pathways by 105-dB and 500-Hz tone pips. Acoustic stimuli included a novel masked stimulus that reduced auditory perception while preserving vestibular activation. Sound-induced vestibular stimulation elicited reliable short- and middle-latency vEP components. Importantly, middle-latency components Na/Pa (peak latency: 20-30 ms) and N*/P* (41-54 ms) were modulated by body orientation, showing reduced amplitudes in the supine compared with the upright position, but only for otolithic-activating sounds and not for matched auditory control stimuli. This orientation-dependent modulation was stronger for Na/Pa and was specific to otolithic-activating sounds, supporting a vestibular rather than auditory origin and highlighting early integration processes. This pattern suggests that modulation of vEPs primarily reflects context-dependent cerebral processing of otolithic signals rather than peripheral sensory mechanisms. Together, our results establish Na/Pa and N*/P* as reliable cerebral markers of otolithic processing and demonstrate that early cerebral vestibular responses are dynamically shaped by body orientation according to gravity.<b>NEW & NOTEWORTHY</b> This study identifies middle-latency vestibular-evoked potentials as reliable cerebral markers of otolithic information processing. We show that both Na/Pa and N*/P* are selectively modulated by body orientation for otolithic-activating sounds but not for auditory controls. These findings reveal that early otolithic vestibular processing depends on body orientation, extending current models of multisensory vestibular integration.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"865-883"},"PeriodicalIF":2.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148604184","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":"Practice-dependent refinement of motor execution is retained and broadly transferable but constrained by movement direction.","authors":"Raphael Q Gastrock, Setayesh Nezakatiolfati, Denise Y P Henriques","doi":"10.1152/jn.00124.2026","DOIUrl":"10.1152/jn.00124.2026","url":null,"abstract":"<p><p>Practice enhances motor acuity, enabling movement execution with greater speed and accuracy. However, the learning principles underlying improvements in speed, accuracy, and efficiency remain relatively understudied compared with those supporting motor skill acquisition and adaptation. Here, we examined motor execution in a skill-based practice task to characterize learning, retention, and generalization of motor acuity. Using a gamified two-dimensional racing task, right-handed participants controlled a stylus-driven car along a curved track as quickly and accurately as possible. Across two studies (<i>n</i> = 83 total, 54 females), participants completed 300 training laps on <i>session 1</i> and returned for <i>session 2</i> to assess retention and generalization to novel track configurations: one with altered spatial configuration (rotated track) and one requiring movement in the opposite direction of training (reverse track). Movement speed improved rapidly, showing robust though incomplete retention across sessions. Speed improvements generalized substantially to both novel tracks. Accuracy was high at training onset and showed strong retention. However, we observed no evidence of offline gains between sessions. Notably, both speed and accuracy declined transiently for the novel track configurations compared with prior training. Movement efficiency, indexed by path length, was retained and generalized to the rotated track. However, reversing movement direction impaired efficiency, revealing a movement direction effect. This effect persisted when training direction was reversed in a second study, with counterclockwise movements remaining slower and less efficient than clockwise movements. Thus, practice produces durable and broadly transferable motor execution improvements, whereas inherent movement direction biases constrain how improvements generalize across contexts.<b>NEW & NOTEWORTHY</b> The learning principles underlying motor acuity improvements are relatively understudied compared with those in motor skill acquisition and adaptation. Prior work suggests that motor execution improvements show limited generalization. In contrast, we demonstrate that execution-based practice can produce robust, transferable gains, while also revealing a key constraint: inherent movement direction biases that limit generalization. By characterizing learning, retention, and generalization, this work provides insight into how motor acuity improvements compare with skill acquisition and adaptation.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"1086-1097"},"PeriodicalIF":2.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794446","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":"Comparison of forelimb and hindlimb movements during treadmill and overground locomotion at different speeds in intact adult cats.","authors":"Johannie Audet, Gabriella Tonleu Dongmo, Charly G Lecomte, Sirine Yassine, Rasha Al Arab, Stephen Mari, Angèle N Merlet, Oussama Eddaoui, Juliette Caron-Davis, Juliana Loza-Vaqueiro, Jean-Christophe Laliberté, Jonathan Harnie, Charlène Nadeau, Alain Frigon","doi":"10.1152/jn.00240.2026","DOIUrl":"10.1152/jn.00240.2026","url":null,"abstract":"<p><p>To evaluate locomotion, motorized treadmills have been widely used in research due to several advantages over conventional overground locomotion. Although comparisons have been made, whether locomotion is equivalent on the treadmill and overground at different speeds remains poorly understood. In the present study, we collected kinematic and electromyography (EMG) data in 10 intact adult cats at four matched speeds ranging from 0.5 m/s to 0.8 m/s during motorized treadmill and overground locomotion. During treadmill locomotion, fore- and hindlimb cycle and stance durations were longer, whereas swing duration was reduced at matched speeds. Cats preferred more stable support periods (i.e., with more limbs on the ground), such as triple and quadrupedal support during treadmill locomotion, whereas they favored diagonal support during overground locomotion, which is known to contribute to forward propulsion and locomotor efficiency. The type of gait and footfall pattern was conserved between locomotor tasks. The fore- and hindlimbs took longer steps and strides during overground locomotion, but paw placement at contact was more rostral during treadmill locomotion. Forelimb and hindlimb extensor muscle burst durations likely reflect the proportionally longer stance phase observed during treadmill locomotion. EMG burst amplitude was greater in fore- and hindlimb extensor muscles during overground locomotion, whereas EMG burst amplitude of flexor muscles was greater during treadmill locomotion. Overall, our findings demonstrate distinct neuromechanical strategies between treadmill and overground locomotion, reflecting differences in stability requirements, propulsion, braking, and fore- and hindlimb positioning in quadrupedal mammals.<b>NEW & NOTEWORTHY</b> This study provides a comprehensive comparison of treadmill and overground locomotion at different matched speeds in intact cats using kinematic and electromyographic analyses of both the forelimbs and hindlimbs. We highlight differences in locomotor strategies during treadmill and overground locomotion in both the fore- and hindlimbs. These findings demonstrate that locomotor task influences control strategies and should be carefully considered when interpreting experiments, particularly in preclinical models of spinal cord injury.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"1146-1161"},"PeriodicalIF":2.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794254","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":"Multiplexed encoding of frequency-modulated sweep features in the inferior colliculus.","authors":"Audrey C Drotos, Sarah Z Wajdi, Michael Malina, Marina A Silveira, Ross S Williamson, Michael T Roberts","doi":"10.1152/jn.00117.2026","DOIUrl":"10.1152/jn.00117.2026","url":null,"abstract":"<p><p>Within the central auditory pathway, the inferior colliculus (IC) is a critical integration center for ascending sound information. Although IC neurons have well-characterized receptive fields for individual sound features such as sound frequency, intensity, and location, growing evidence suggests that some neurons also use multiplexing to encode sound feature combinations. Here, we performed in vivo juxtacellular recordings in awake, head-fixed mice to examine how individual IC neurons and neuronal populations encode the speed, direction, and frequency range of frequency-modulated (FM) sweeps. To understand the strategies used by neurons to represent different sound features, we trained a support vector machine to decode sound features from different parameters of the spike train, including the firing rate, spike times relative to stimulus onset, distribution of inter-spike intervals, and first spike latency. We found that many IC neurons multiplex features of FM sweeps using distinct temporal coding strategies rather than simple changes in mean firing rate, and that these feature representations are interdependent, yielding a combinatorial encoding of sound features within individual neurons. Accordingly, using static receptive fields for sweep frequency or direction alone yielded poor predictions of neuron responses to vocalizations that contain simple frequency changes. Finally, we showed that encoding strategies varied across individual neurons, resulting in a highly informative population code for FM sweep parameters. Together, our results suggest that multiplexing is a common mechanism used by IC neurons to represent complex sound features.<b>NEW & NOTEWORTHY</b> The inferior colliculus (IC) is a critical auditory processing center. IC neurons exhibit diverse responses to different sound features, but how IC neurons encode co-varying sound features-such as both the direction and intensity of a frequency-modulated (FM) sweep-is poorly understood. Here, we show that individual IC neurons and neuronal populations multiplex information about FM sweep direction, frequency range, and speed through distinct coding strategies, including both spike timing patterns and overall firing rate.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"1024-1044"},"PeriodicalIF":2.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13573665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148673815","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":"Comprehensive analysis of auditory nerve fiber responses using fiber-specific modeling.","authors":"Rebecca C Felsheim, David J Sly, Stephen J O'Leary, Mathias Dietz","doi":"10.1152/jn.00044.2026","DOIUrl":"10.1152/jn.00044.2026","url":null,"abstract":"<p><p>One important aspect of improving cochlear implant performance is a good, quantitative understanding of electrically stimulated nerve fibers and the effects of deafness on their behavior. The main principles of a nerve fiber's responses are well understood. The measures describing the responses, such as the refractory period or facilitation, and the effects of deafness on them, have been investigated in different publications and nerve fiber populations. However, a comprehensive analysis of many measures based on a single dataset is still lacking. Using a fiber-specific model-based analysis, we show that it is possible to extract multiple measures from existing pulse train recordings of 118 guinea-pig nerve fibers. This not only included eight basic measures, such as refractory period and facilitation, but also four spike-train-derived measures (spike rate, dip duration, interspike interval, and vector strength). Using these, we started two lines of investigation. In the first one, we investigated the response differences between fibers from acutely and chronically deafened animals. The results showed that, on average, the chronically deaf groups had a shorter refractory period and a higher discharge rate. In the second line, we investigated the relationship between the basic measures and the spike-train measures using fiber-specific modeling. This showed, e.g., an inverse relationship between the spike rate and the refractory period, confirming our previous findings. Overall, this paper provides a detailed characterization of both acutely and chronically deafened nerve fibers, and an analysis of the interaction between basic measures and spike-train responses.<b>NEW & NOTEWORTHY</b> Quantitative descriptions of electrically evoked auditory nerve responses are essential for improving cochlear implants. Using fiber-specific modeling, this study extracts a comprehensive set of response measures from pulse-train recordings of 118 auditory nerve fibers. Comparing fibers from acutely and chronically deafened animals reveals differences, e.g., in refractory properties and response rate. An investigation into the relationship between the measures revealed a dependency of the rate on the refractory properties and additionally on the dynamic range.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"518-532"},"PeriodicalIF":2.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148375965","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":"Approaching hurricane effects on phrenic motor plasticity: the Florida experience.","authors":"Alexandria B Marciante, Alec L E Butenas, Kayla A Burrowes, Gordon S Mitchell","doi":"10.1152/jn.00157.2026","DOIUrl":"10.1152/jn.00157.2026","url":null,"abstract":"<p><p>Phrenic long-term facilitation (pLTF) is a form of respiratory motor plasticity elicited by moderate acute intermittent hypoxia (mAIH). Although certain factors such as aging and inflammation undermine mAIH-induced pLTF, little is known concerning the effects of physiological stress. Over several decades, accumulated anecdotal evidence from our laboratory suggests that major construction near the animal facility, or other events thought to elicit stress responses in rats, undermine mAIH-induced pLTF and cause unstable phrenic bursting accompanied by spontaneous phrenic nerve \"apneas\" post-AIH; the reasons for stress-induced instability are unknown. Here, we document chance observations of similar effects on phrenic nerve activity during the 2024 Florida hurricane season. Approaching hurricanes ±5 days from landfall in Florida were associated with unstable phrenic nerve activity, neural apneas, and increased serum stress hormone levels in anesthetized adult (3-4 mo) male Sprague-Dawley rats. We summarize observations concerning the impact of hurricanes and discuss the role of stress hormones, underscoring the need to consider factors known to elevate stress hormones in studies of respiratory control, including respiratory motor plasticity.<b>NEW & NOTEWORTHY</b> Over several decades, anecdotal evidence from our laboratory suggests that stress undermines respiratory (phrenic) motor plasticity elicited by acute intermittent hypoxia and destabilizes phrenic nerve activity for unknown reasons. During the 2024 Florida Hurricane Season, we observed that approaching hurricanes were associated with unstable phrenic nerve activity, neural apneas, and increased serum stress hormone levels, highlighting the need to consider factors known to elevate stress hormones in studies of breathing stability and/or neuroplasticity.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"546-556"},"PeriodicalIF":2.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148436809","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":"Stability of ruthenium oxide-coated microelectrode arrays for chronic stimulation of rat somatosensory cortex.","authors":"Thomas J Smith, Hari Srinivasan, Sophia L Vargas, Mahasty Khajehzadeh, Eleanor N Jeakle, Shreya Tirumala Kumara, Madison Jiang, Ashlynn Ogundipe, Luisa R Villafranca, Mehak Kaul, Arlin A Khan, Claire Cheon, Mihai Bendea, Fareeha Faruk, Ghazaal Tahmasebi, Justin Abbott, Andrew Barre, Ana G Hernandez-Reynoso, Joseph J Pancrazio, Stuart F Cogan","doi":"10.1152/jn.00047.2026","DOIUrl":"10.1152/jn.00047.2026","url":null,"abstract":"<p><p>Intracortical microstimulation (ICMS) of the primary somatosensory cortex offers the potential for restoring sensory function in neuroprosthetic applications; however, achieving stable long-term performance from implanted electrode materials remains a challenge. Recently, ruthenium oxide (RuO_x) has emerged as a viable faradaic coating material suitable for ICMS application due to its high-charge injection capacity, low impedance, and stable electrochemical properties. However, its long-term in vivo performance remains an area of active investigation. In this study, we evaluated the viability of RuO_x-coated amorphous silicon carbide microelectrode arrays (MEAs) for producing ICMS-evoked percepts over a 25-wk chronic implantation period with an established rodent-based go/no-go behavioral paradigm. Weekly behavioral, electrochemical, and local electrophysiological measurements were analyzed to assess the stability of RuO_x for long-term stimulation and recording studies. Results showed an exponential-like reduction in perception thresholds, stabilizing around the ninth postimplantation week at ∼0.4 nC/ph per electrode ×16 electrodes (simultaneous multichannel stimulation). Throughout this period, behavioral performance remained consistently high (∼91%), with stable reaction times, indicating reliable sensory perception up to 25 wk. Electrochemical measurements, including 1-kHz impedance and driving voltage, alongside neural recording metrics like spike rate and noise floor, remained relatively stable throughout the study. Although minor degradations in the number of detected units per electrode and the peak-to-peak voltages of those units were observed (consistent with other silicon-based MEA studies), RuO_x-coated electrodes demonstrated the ability to reliably evoke sensory percepts over the duration of the experiment. Overall, these findings highlight RuO_x as a durable MEA-coating material for future ICMS applications.<b>NEW & NOTEWORTHY</b> Ruthenium oxide has emerged as a promising electrode coating material for intracortical microstimulation applications due to its favorable electrochemical properties. However, its long-term in vivo stimulation performance has not been well characterized. Using a go/no-go behavioral paradigm, we show that ruthenium oxide-coated microelectrode arrays support functionally relevant intracortical microstimulation-induced percepts for up to 25 wk postimplantation in rat somatosensory cortex, highlighting stable electrochemical properties and the utility of ruthenium oxide for chronic applications.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"854-863"},"PeriodicalIF":2.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148604119","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":"Persistent input- and cell-type-specific synaptic alterations in the somatosensory thalamus of Dravet syndrome mice.","authors":"Mona Safari, Rutvi Pallav Desai, Harbal Rai, Tyler J Roberts, Rabeya Khondaker, Julia Smith, Sharon A Swanger","doi":"10.1152/jn.00064.2026","DOIUrl":"10.1152/jn.00064.2026","url":null,"abstract":"<p><p>Dravet syndrome (DS) is an epileptic encephalopathy most often caused by loss-of-function mutations in the <i>SCN1A</i> gene, leading to haploinsufficiency of the voltage-gated sodium channel Na_V1.1. Seizures begin during infancy and wane throughout childhood, but behavioral symptoms, including intellectual disability, motor impairments, and autistic features, remain through adulthood. Seizures primarily stem from inhibitory neuron hypoexcitability in the cortex, hippocampus, and thalamus, but circuit abnormalities underlying persistent behavioral symptoms are poorly understood. Prior work showed synapse dysfunction in thalamocortical neurons in 4-wk-old DS mice, but elucidating the timing and progression of these alterations is necessary to understand the disease stages that synapse dysfunction may contribute to circuit and behavioral phenotypes. We investigated synapse function in the ventral posterolateral (VPL) and ventral posteromedial (VPM) thalamus before seizure onset (P13-P17), after the period of highest seizure burden (P28-P32), and in adulthood (P58-P63). VPL and VPM synaptic activity showed that excitatory input to the VPL was reduced after seizure onset, and this reduction persisted through adulthood, while VPM excitatory input was unaffected. We further showed a selective reduction in the function and number of excitatory sensory synapses in the VPL, with no change to cortical synapses. VPL and VPM neurons both showed inhibitory synapse dysfunction at 4 wk, which persisted in adult DS mice only in VPL neurons. These results revealed persistent input- and cell-type-specific alterations to thalamic synapses that develop after seizure onset and are maintained into adulthood, suggesting synaptic deficits could contribute to ongoing somatosensory thalamocortical circuit dysfunction and behavioral deficits in DS.<b>NEW & NOTEWORTHY</b> This study reveals that synaptic dysfunction in the somatosensory thalamus of Dravet syndrome (DS) mice emerges after seizure onset and persists into adulthood. Using electrophysiology and high-resolution imaging, we demonstrate a selective, persistent reduction of sensory input to VPL neurons, while cortical input remains intact. Inhibitory input to VPL thalamus is similarly impaired after seizure onset and persists in adulthood. These input- and cell-type-specific deficits may contribute to the enduring sensory and sleep impairments characteristic of DS.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"558-574"},"PeriodicalIF":2.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13533332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148421833","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}