Journal of Neuroscience最新文献

{"title":"Collapsing perisomatic inhibition leads to epileptic fast ripple oscillations caused by pseudosynchronous firing of CA3 pyramidal neurons.","authors":"Dániel Schlingloff,Tamás F Freund,Balázs Hangya,Attila Gulyás","doi":"10.1523/jneurosci.0500-25.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.0500-25.2025","url":null,"abstract":"Diverse network oscillations, thought to represent different information processing modes of cortical networks, are accompanied by synchronous neuronal activity at various temporal scales. Sharp wave associated ripple oscillations, supporting memory consolidation in the hippocampus, are among the fastest physiological oscillations characterized by strong inter-neuronal synchrony. In contrast, when hippocampal activity turns epileptic, pathological fast-ripple oscillations appear. The distinction of the two oscillations is diagnostically relevant; however, how differential mechanisms of the same network generate the two activities is not well understood. Here we addressed this question using an in vitro hippocampal model that allowed targeted recording of cell types and local pharmacological manipulations in mice of either sex. We showed that inhibition did not contribute to current and rhythm generation of fast-ripples, unlike physiological ripple oscillations. Instead, pathological fast-ripples emerged when perisomatic inhibition from parvalbumin-expressing basket cells collapsed and depended on the quasi-simultaneous onset of stereotypical pyramidal cell (PC) bursts leading to pseudosynchrony. This was accompanied by a loss of spatial coherence. In epileptogenic conditions, deep CA3 PCs selectively ramped up their burst activity before fast-ripple onset, while normally non-bursting superficial PCs acquired burst capability. These results point to PC pseudosynchrony as the underlying mechanism of fast-ripples, with differential contribution of known PC types.Significance statement Sharp wave-ripple oscillations in the hippocampus support memory consolidation via coordinated inhibition-driven synchrony, whereas pathological fast-ripples mark epileptogenic activity. Using an in vitro hippocampal model in mice, we show that fast-ripples emerge from pseudo-synchronous bursting of pyramidal cells after perisomatic inhibition collapses. Deep pyramidal cells of the CA3 area of hippocampus ramp up bursting activity before fast-ripple onset, while normally non-bursting superficial cells fire bursts under epileptic conditions. In contrast to ripple oscillations, fast-ripples lack rhythmic inhibition and exhibit degraded spatial coherence. These findings reveal cell type-specific excitability changes and implicate local failure of inhibition and loss of coherence as mechanisms driving fast-ripple emergence.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"27 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145209321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co-release of GABA and ACh from medial olivocochlear neurons as a fine regulatory mechanism of cochlear efferent inhibition.","authors":"Tais Castagnola,Valeria C Castagna,Lester Torres Cadenas,Siân R Kitcher,Mariano N Di Guilmi,María E Gomez Casati,Holly J Beaulac,Paula I Buonfiglio,Viviana Dalamón,Eleonora Katz,Ana Belén Elgoyhen,Catherine J C Weisz,Juan D Goutman,Carolina Wedemeyer","doi":"10.1523/jneurosci.1653-24.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.1653-24.2025","url":null,"abstract":"During development, inner hair cells (IHCs) in the mammalian cochlea are unresponsive to acoustic stimuli but instead exhibit spontaneous activity. During this same period, neurons originating from the medial olivocochlear (MOC) complex transiently innervate IHCs, regulating their firing pattern which is crucial for the correct development of the auditory pathway. Although the MOC-IHC is a cholinergic synapse, previous evidence indicates the widespread presence of gamma-aminobutyric acid (GABA) signaling markers, including presynaptic GABAB receptors (GABABR). In this study, we explore the source of GABA by optogenetically activating either cholinergic or GABAergic fibers. The optogenetic stimulation of MOC terminals from GAD;ChR2-eYFP and ChAT;ChR2-eYFP mice (of either sex) evoked synaptic currents in IHCs, which were blocked by α-bungarotoxin. This suggests that GABAergic fibers release acetylcholine (ACh) and activate α9α10 nicotinic acetylcholine receptors (nAChRs). Additionally, MOC cholinergic fibers release not only ACh but also GABA, as the effect of GABA on ACh response amplitude was prevented by applying a GABABR blocker. Using optical neurotransmitter detection and calcium imaging techniques, we examined the extent of GABAergic modulation at the single synapse level. Our findings suggest heterogeneity in GABA modulation, as only 15 out of 31 recorded synaptic sites were modulated by applying the GABABR specific antagonist, CGP 35348 (100-200 µM). In conclusion, we provide evidence indicating that GABA and ACh are co-released from at least a subset of MOC terminals. In this circuit, GABA functions as a negative feedback mechanism, locally regulating the extent of cholinergic inhibition at certain efferent-IHC synapses during an immature stage.Significance statement Before hearing onset, the medial olivocochlear (MOC) efferent system of the mammalian cochlea regulates the pattern of IHC spontaneous firing rate through the activation of α9α10 nAChRs. However, GABA is also known to have a modulatory role at the MOC-IHC synapse. Our results suggest that GABA is co-released from at least a subset of MOC terminals, working as a precise regulatory mechanism for ACh release. Furthermore, we demonstrate that not all synaptic contacts within a single IHC are equally modulated by GABA.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"100 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145209304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disentangling the functional roles of premotor-motor pathways in automatic imitation: A combined network-based transcranial stimulation and drift diffusion modeling approach.","authors":"Sonia Turrini,Luca Tarasi,Naomi Bevacqua,Francesca Fiori,Sara Zago,Giorgio Arcara,Matteo Candidi,Vincenzo Romei,Alessio Avenanti","doi":"10.1523/jneurosci.0340-25.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.0340-25.2025","url":null,"abstract":"Humans have an automatic tendency to imitate others' actions, a process facilitated by the action observation network (AON). While motor nodes of the AON, such as the ventral premotor cortex (PMv) and the supplementary motor area (SMA), are engaged during automatic imitation, the distinct roles of their projections to the primary motor cortex (M1) remain poorly understood. Here, we investigate the plasticity and functional role of PMv-to-M1 and SMA-to-M1 pathways in healthy humans of either sex. We used a combination of cortico-cortical paired associative stimulation (ccPAS) to modulate cortical connectivity strength, and drift diffusion modeling (DDM) to study the impact of ccPAS on the latent cognitive processes underlying automatic imitation. Our results show that manipulating PMv-to-M1 connectivity increases the baseline tendency to imitate actions, shifting the response toward or away from an imitative response when connectivity in this circuit is enhanced or hindered, respectively. Conversely, strengthening SMA-to-M1 connectivity does not affect this bias but improves contextual information integration, facilitating task-appropriate behavior, reflected by the drift rate parameter. These findings demonstrate a double dissociation in the functional roles of PMv-to-M1 and SMA-to-M1 pathways: the former pathway drives the automatic imitation bias, while the latter modulates the integration of contextual information to regulate imitation. By combining network-based brain stimulation with advanced behavioral analysis, this study provides causal evidence for the distinct cognitive functions supported by the PMv-to-M1 and SMA-to-M1 pathways in the facilitation and regulation of automatic imitation. Our findings offer insights into the neural mechanisms governing imitation and its context-dependent modulation.Significance statement Humans automatically imitate others' actions, a process supported by fronto-parietal brain regions. However, the specific roles of the ventral premotor to primary motor cortex (PMv-to-M1) and supplementary motor area to primary motor cortex (SMA-to-M1) pathways are unclear. Using cortico-cortical paired associative stimulation (ccPAS) and drift diffusion modeling (DDM), we demonstrate a double dissociation in the functions of these networks. PMv-to-M1 connectivity determines the baseline tendency to imitate (i.e., starting point parameter), either increasing or reducing automatic imitation. In contrast, SMA-to-M1 connectivity enhances integration of contextual information, promoting task-appropriate responses (i.e., drift rate parameter). These findings highlight distinct contributions of PMv-to-M1 and SMA-to-M1 pathways to imitation and its regulation, advancing our understanding of the neural mechanisms underlying social behavior.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"7 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145209320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disrupted Calcium Dynamics in Reactive Astrocytes Occur with End Feet-Arteriole Decoupling in an Amyloid Mouse Model of Alzheimer's Disease.","authors":"Blaine E Weiss, John C Gant, Ruei-Lung Lin, Jenna L Gollihue, Colin B Rogers, Susan D Kraner, Edmund B Rucker, Yuriko Katsumata, Yang Jiang, Peter T Nelson, Donna M Wilcock, Pradoldej Sompol, Olivier Thibault, Christopher M Norris","doi":"10.1523/JNEUROSCI.0349-25.2025","DOIUrl":"10.1523/JNEUROSCI.0349-25.2025","url":null,"abstract":"<p><p>While cerebrovascular dysfunction and reactive astrocytosis are extensively characterized hallmarks of Alzheimer's disease (AD) and related dementias, the dynamic relationship between reactive astrocytes and cerebral vessels remains poorly understood. Here, we used jGCaMP8f and two-photon microscopy to investigate calcium signaling in multiple astrocyte subcompartments, concurrent with changes in cerebral arteriole activity, in fully awake 7- to 8-month-old male and female 5xFAD mice, a model for AD-like pathology, and wild-type (WT) littermates. In the absence of movement, spontaneous calcium transients in barrel cortex occurred more frequently in astrocyte somata, processes, and perivascular regions of 5xFAD mice. However, evoked arteriole dilations (in response to air puff stimulation of contralateral whiskers) and concurrent calcium transients across astrocyte compartments were reduced in 5xFAD mice relative to WTs. Synchronous activity within multicell astrocyte networks was also impaired in the 5xFAD group. Using a custom application to assess functional coupling between astrocyte end feet and immediately adjacent arteriole segments, we detected deficits in calcium response probability in 5xFAD mice. Moreover, end feet calcium transients following arteriole dilations exhibited a slower onset, reduced amplitude, and lacked relative proportionality to vasomotive activity compared with WTs. The results reveal nuanced alterations in 5xFAD reactive astrocytes highlighted by impaired signaling fidelity between astrocyte end feet and cerebral arterioles. The results have important implications for the mechanistic underpinnings of brain hypometabolism and the disruption of neurophysiologic communication found in AD and other neurodegenerative conditions.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12491769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute Restraint Stress and Pain Modulation Depend on the Interaction between the Periaqueductal Gray and the Lateral Septum.","authors":"Devanshi Piyush Shah, Yatika Chaudhury, Arnab Barik","doi":"10.1523/JNEUROSCI.2257-24.2025","DOIUrl":"10.1523/JNEUROSCI.2257-24.2025","url":null,"abstract":"<p><p>Acute restraint stress (RS) causes analgesia in humans and laboratory animals, but the underlying mechanisms are unknown. Recently, we have shown that a multinodal circuitry between the dorsal lateral septum (dLS), lateral hypothalamic area (LHA), and rostral ventromedial medulla (RVM) plays an instructive role in RS-induced analgesia (SIA). We found that the dLS neurons are activated when mice struggle to escape the restraint, and we wondered about the origin of the escape signals. Hence, we performed retrograde viral labeling from the dLS and found that the ventrolateral periaqueductal gray (vlPAG), a known anatomical substrate for escape behaviors, provides inputs to the dLS. Through anatomical, behavioral, and in vivo fiber photometry, we show that the PAG and dLS neurons are synaptically connected; activation of either PAG or the postsynaptic dLS neurons is sufficient to cause analgesia and, when inhibited, cause hyperalgesia. Moreover, we found that the dLS neurons that receive inputs from PAG send axonal projections to the LHA. Together, our data indicate that the vlPAG neurons encoding nociceptive and escape behaviors provide synaptic inputs to the dLS-LHA-RVM circuitry to mediate acute restraint SIA in both male and female mice.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12491763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144977067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Somatostatin Pathway Projected from the Basal Forebrain to the Lateral Habenula Promotes Isoflurane Anesthesia Recovery.","authors":"Ying Wang, Zhimin Wang, Mao Xu, Jiamin Wang, Shuang Cai, Danxu Zheng, Aichen Tang, Tian Yu, Yuan Wang, Tianyuan Luo, Shouyang Yu","doi":"10.1523/JNEUROSCI.1316-24.2025","DOIUrl":"10.1523/JNEUROSCI.1316-24.2025","url":null,"abstract":"<p><p>The basal forebrain (BF) acts as a pivotal relay station in the transmission of arousal signals, projecting to both cortical and subcortical structures. Among its downstream targets is the lateral habenula (LHb), which recent research has implicated in the modulation of sleep rhythms and in mediating the loss of consciousness associated with anesthetic agents. In our study, we utilized optogenetic manipulation to selectively modulate the BF^VGluT2/SOM neuron projection pathway to the LHb, thereby examining its impact on behavioral and electroencephalographic responses to isoflurane anesthesia. Our results demonstrated that in healthy adult male mice, the activation of the BF^SOM→LHb projection pathway significantly prolonged the induction time of anesthesia and shortened recovery time, consequently diminishing the anesthetic potency of isoflurane and reducing EEG <i>δ</i> power. In contrast, the inhibition of this pathway yielded the inverse effects. Notably, modulation of the BF^VGluT2→LHb projection pathway did not significantly affect the induction or recovery times of isoflurane anesthesia. Employing optogenetics in conjunction with calcium signal recording, we elucidated that the arousing effect of the BF^SOM→LHb pathway is attributable to the enhanced inhibitory action of BF^SOM neurons on LHb^Glu neurons. This discovery sheds new light on the neural circuits involved in the loss and recovery of consciousness induced by anesthetic drugs, potentially informing future therapeutic strategies.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144976861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Annual Renewal: Why the Society for Neuroscience Meeting Keeps Drawing Me Back","authors":"Indira M. Raman","doi":"10.1523/jneurosci.1524-25.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.1524-25.2025","url":null,"abstract":"<p>Registering for my 35th consecutive Society for Neuroscience Annual Meeting in early July 2025, I realized the Conference is the longest standing yearly ritual of my life. I couldn't help wondering, why do I keep doing it? Is it duty or desire, an act of fidelity or of faith? And is it worth it?</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"40 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145195156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stopping Muscle Contractions and Relaxations during Action Inhibition Involves Global and Targeted Control Dependent on Muscle State.","authors":"Jack De Havas, Jaime Ibañez, Hiroaki Gomi, Sven Bestmann","doi":"10.1523/JNEUROSCI.1170-25.2025","DOIUrl":"10.1523/JNEUROSCI.1170-25.2025","url":null,"abstract":"<p><p>The mechanisms underpinning the stopping of muscle contractions and relaxations during action inhibition remain unclear. Central stop commands may be targeted and act on task-active muscles only, or instead be global, acting on task-passive muscles as well. We addressed this question in three stop signal task experiments with human participants (<i>n</i> = 54; 18 male, 36 female). While maintaining baseline force levels (10% MVC) in both index fingers, Go signals required participants to increase or decrease this force in the task-active finger (Task-active Contract vs Task-active Relax) while keeping activity in the task-passive muscle constant. On 30% of trials, delayed stop signals instructed participants to stop the task-active responses. Stop-related activity was detected in task-active muscles at the single trial level, using electromyography (EMG), and used to determine whether stop-related activity was also present in task-passive muscles. We found that stop commands act on both task-active and task-passive muscles, suggesting global control. This global control was furthermore muscle state specific, by decreasing muscle activity when stopping contractions and increasing muscle activity when stopping relaxations. However, stopping muscle contractions involved more sustained suppression of muscle activity in task-active than task-passive muscles, suggesting additional targeted control. This was not the case when stopping muscle relaxations, which only showed evidence of global control. Our results may explain how complex, real-world actions are inhibited. Global stop commands that are sensitive to muscle state may rapidly adjust muscle activity across the body, with additional control targeted to contracting, task-active muscles.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12491765/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144884191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of Long-Term Nonexternally Reinforced Preference Change: Functional Connectivity Changes in a Longitudinal Functional MRI Study.","authors":"Alon Itzkovitch, Shiran Oren, Sidhant Chopra, Alex Fornito, Tom Schonberg","doi":"10.1523/JNEUROSCI.0702-25.2025","DOIUrl":"10.1523/JNEUROSCI.0702-25.2025","url":null,"abstract":"<p><p>Behavioral change studies mostly focus on external reinforcements to modify preferences. Cue-approach training (CAT) is a paradigm that influences preferences by the mere association of stimuli, sensory cues, and a rapid motor response, without external reinforcements. The behavioral effect has been shown to last for months after less than 1 h of training. Here, we used a modified version of CAT by changing the neutral-cue to a number that represented a monetary amount of reward that the participants accumulate (i.e., incentive-cue). After a single training session, we compared behavioral performance and functional connectivity (FC), as measured by resting-state scans using functional magnetic resonance imaging, between two groups (total of 107 males and females in both groups), one receiving a neutral-cue and the other receiving an incentive-cue, at five time points across 1 year. We replicated the maintenance of behavioral changes after 6 months for the nonexternally reinforced neutral-cue participants, but not for the reinforced group. The reinforced training group showed higher FC within the limbic system, whereas the nonexternally reinforced group showed higher functional connectivity within and between default mode and dorsal attention networks. Our findings offer putative neural correlates for both reinforced and nonexternally reinforced preference changes that are maintained over time and which could be implemented in future behavioral change interventions.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12491771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144976756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Extralemniscal System Modulates Early Somatosensory Cortical Processing.","authors":"Sofija Perovic, Richard Somervail, Diego Benusiglio, Gian Domenico Iannetti","doi":"10.1523/JNEUROSCI.1815-24.2025","DOIUrl":"10.1523/JNEUROSCI.1815-24.2025","url":null,"abstract":"<p><p>Sudden and surprising sensory changes signal environmental events that may require immediate behavioral reactions. In mammals, these changes engage nonspecific \"extralemniscal\" thalamocortical pathways and evoke large and widespread cortical vertex potentials (VPs). Extralemniscal activity modulates cortical motor output in a variety of tasks and facilitates purposeful and immediate behavioral responses. In contrast, whether the extralemniscal system also affects cortical processing of sensory input transmitted through canonical \"lemniscal\" thalamocortical pathways remains unknown. Here we tested this hypothesis. In 23 healthy human participants (11 females) we continuously probed lemniscal processing in the primary somatosensory cortex (S1) by measuring the early-latency evoked potentials elicited by a stream of high-frequency (9.5 Hz) somatosensory electrical stimuli. We concurrently recorded extralemniscal activity by measuring the large VPs elicited by fast-rising and infrequent (∼0.1 Hz) auditory pure tones. We observed that the amplitude of S1 responses changes as a function of the phase of the VP, an effect consequent to a modulation of lemniscal input at the cortical rather than subcortical level. These findings demonstrate that a transient activation of the extralemniscal system interferes with ongoing cortical functions across different brain systems-i.e., not only at the level of the motor output but already at the sensory input-and thereby influences global brain dynamics.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12491762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144849535","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}