Jia-Qing Tong, Jeffrey R Binder, Lisa L Conant, Stephen Mazurchuk, Andrew J Anderson, Leonardo Fernandino
{"title":"A Common Representational Code for Event and Object Concepts in the Brain.","authors":"Jia-Qing Tong, Jeffrey R Binder, Lisa L Conant, Stephen Mazurchuk, Andrew J Anderson, Leonardo Fernandino","doi":"10.1523/JNEUROSCI.2166-24.2025","DOIUrl":"10.1523/JNEUROSCI.2166-24.2025","url":null,"abstract":"<p><p>Events and objects are two fundamental ways in which humans conceptualize their experience of the world. Despite the significance of this distinction for human cognition, it remains unclear whether the neural representations of object and event concepts are categorically distinct or, instead, can be explained in terms of a shared representational code. We investigated this question by analyzing fMRI data acquired from human participants (males and females) while they rated their familiarity with the meanings of individual words (all nouns) denoting object and event concepts. Multivoxel pattern analyses indicated that both categories of lexical concepts are represented in overlapping fashion throughout the association cortex, even in the areas that showed the strongest selectivity for one or the other type in univariate contrasts. Crucially, in these areas, a feature-based model trained on neural responses to individual event concepts successfully decoded object concepts from their corresponding activation patterns (and vice versa), showing that these two categories share a common representational code. This code was effectively modeled by a set of experiential feature ratings, which also accounted for the mean activation differences between these two categories. These results indicate that neuroanatomical dissociations between events and objects emerge from quantitative differences in the cortical distribution of more fundamental features of experience. Characterizing this representational code is an important step in the development of theory-driven brain-computer interface technologies capable of decoding conceptual content directly from brain activity.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144976989","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":"Space impacts temporal processing via a visual-dependent spatially organized neural architecture.","authors":"Maria Bianca Amadeo,Cristiano Cuppini,Alessia Tonelli,Carolina Tammurello,Walter Setti,Claudio Campus,Sabrina Signorini,Elena Cocchi,Margherita Bonino,Francesca Tinelli,Paola Camicione,Massimiliano Serafino,Monica Gori","doi":"10.1523/jneurosci.1444-24.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.1444-24.2025","url":null,"abstract":"Establishing the temporal relationship between stimuli challenges the brain, requiring some tolerance for asynchronies to form coherent representations. Based on the theory of implicit causal inference, we hypothesized temporal processing of events is influenced by spatial features as stimuli coming from the same spatial location are most likely to derive from a common source and, consequently, implicitly merged in time. As visual experience guides the formation of neural sensory maps, we expected the spatial influence on temporal processing to depend on visual experience. In Experiment 1, 41 sighted children and adults (22 females) judged the temporal order of auditory and tactile stimuli delivered to the same or different hands (somatotopic manipulation), with hands either close or far apart (spatiotopic manipulation). In Experiment 2, sighted individuals (15 females) were compared with 26 early blind children and adults (12 females) during the somatotopic manipulation with hands far apart. Results revealed an improvement of temporal resolution with age in sighted individuals, while blind children performed similarly to adults. Notably, spatial features affected the temporal processing of sighted but not blind people, regardless of age. Sighted participants showed higher temporal tolerance toward asynchronies in the case of somatotopic or spatiotopic congruence. A bioinspired neurocomputational model has been developed to unveil neural mechanisms underlying the interaction between spatial and temporal processing. The model demonstrates that temporal processing is mediated by a spatially organized synaptic architecture, which requires visual experience to develop. Without vision, spatial alignment may not be conceptualized as a prior influencing temporal processing.Significance statement This study demonstrates that spatial features affect temporal resolution of sighted but not blind children and adults. A neurocomputational model suggests these behavioral results stem from spatially organized synaptic connections that require visual experience to develop. This research advances understanding of sensory processes, highlighting the role of vision in developing temporal processing mechanisms, and have implications for interventions in vision impairment.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"10 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145246666","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}
Arefeh Farahmandi, Parisa Abedi Khoozani, Gunnar Blohm
{"title":"Beyond Divisive Normalization: Scalable Feedforward Networks for Multisensory Integration Across Reference Frames.","authors":"Arefeh Farahmandi, Parisa Abedi Khoozani, Gunnar Blohm","doi":"10.1523/JNEUROSCI.0104-25.2025","DOIUrl":"10.1523/JNEUROSCI.0104-25.2025","url":null,"abstract":"<p><p>The integration of multiple sensory inputs is essential for human perception and action in uncertain environments. This process includes reference frame transformations as different sensory signals are encoded in different coordinate systems. Studies have shown multisensory integration (MSI) in humans is consistent with Bayesian optimal inference. However, neural mechanisms underlying this process are still debated. Different population coding models have been proposed to implement probabilistic inference. This includes a recent suggestion that explicit divisive normalization accounts for empirical principles of MSI. However, whether and how divisive operations are implemented in the brain is not well understood. Indeed, all existing models suffer from the curse of dimensionality and thus fail to scale to real-world problems. Here, we propose an alternative model for MSI that approximates Bayesian inference: a multilayer-feedforward neural network of MSI across different reference frames trained on the analytical Bayesian solution. This model displays all empirical principles of MSI and produces similar behavior to that reported in ventral intraparietal neurons in the brain. The model achieved this without a neatly organized and regular connectivity structure between contributing neurons, such as required by explicit divisive normalization. Overall, we show that simple feedforward networks of purely additive units can approximate optimal inference across different reference frames through parallel computing principles. This suggests that it is not necessary for the brain to use explicit divisive normalization to achieve multisensory integration.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12509496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144976078","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}
Lindsay I Rait,Guo Wanjia,Zhifang Ye,Sarah DuBrow,Brice A Kuhl
{"title":"Hippocampal drift rate reflects the temporal organization of memories.","authors":"Lindsay I Rait,Guo Wanjia,Zhifang Ye,Sarah DuBrow,Brice A Kuhl","doi":"10.1523/jneurosci.0909-25.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.0909-25.2025","url":null,"abstract":"When freely recalling events from the past, individuals tend to successively remember stimuli that were studied close together in time-a phenomenon known as temporal clustering. Temporal clustering is thought to occur because stimuli are encoded in relation to a slowly-drifting internal context; this internal context representation is then reinstated during recall, leading to clustered recall of stimuli that share a similar internal context. While several lines of evidence implicate the hippocampus in supporting internal context representations, there is limited evidence directly linking hippocampal drift during memory encoding to subsequent temporal clustering during recall. In a human fMRI experiment (n=38), we sought to influence the rate of internal context change during memory encoding and tested for corresponding effects on (a) temporal clustering and (b) hippocampal drift rate. To influence internal context, we manipulated the rate at which background scenes 'switched' while a list of words was encoded. Afterwards, subjects freely recalled as many words as possible. while switch rate had no effect on the total number of words recalled, it significantly influenced the degree of temporal clustering. Specifically, a higher switch rate was associated with less temporal clustering. Strikingly, this pattern of data was mirrored by drift rate in the hippocampus: a higher switch rate was associated with significantly lower hippocampal autocorrelation (more drift). Moreover, individual differences in hippocampal autocorrelation were positively correlated with temporal clustering. Collectively, these findings suggest that hippocampal drift rate during encoding and temporal clustering during recall each reflect a common internal context representation.Significance Statement The hippocampus is thought to support a gradually-drifting internal context representation that allows memories to be organized in time. This putative internal context representation helps explain the phenomenon of temporal clustering-that events encoded nearby in time are clustered together during recall. Yet, there is surprisingly limited evidence directly linking the drift of hippocampal activity patterns to the phenomenon of temporal clustering. Here, we show that manipulating the rate of external context change during memory encoding induced parallel changes in hippocampal drift rate during encoding and temporal clustering during subsequent recall. Critically, hippocampal drift rate also predicted the degree of temporal clustering across individuals. These findings suggest that hippocampal drift rate and temporal clustering reflect a common internal context representation.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"31 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145241096","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}
Brian J Fischer, Keanu Shadron, Clifford H Keller, Avinash D S Bala, Fanny Cazettes, Roland Ferger, José L Peña
{"title":"Neural responses underlying interaural time difference discrimination as a function of sensory reliability in the barn owl.","authors":"Brian J Fischer, Keanu Shadron, Clifford H Keller, Avinash D S Bala, Fanny Cazettes, Roland Ferger, José L Peña","doi":"10.1523/JNEUROSCI.1145-25.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.1145-25.2025","url":null,"abstract":"<p><p>Discrimination of sensory stimuli is fundamentally constrained by the information encoded in neuronal responses. In the barn owl, interaural time difference (ITD) serves as a primary cue for azimuthal sound localization and is represented topographically in the midbrain auditory space map in the external nucleus of the inferior colliculus (ICx). While prior studies have demonstrated a correspondence between spatial tuning and behavioral acuity, it remains unclear how changes in sensory reliability influence this relationship. Here, we examined how behavioral and neuronal ITD discrimination thresholds vary with binaural correlation (BC), which manipulates ITD cue reliability. Using the pupil dilation response (PDR) as a behavioral metric in head-fixed owls of either sex, we found that ITD just-noticeable-differences increased exponentially as BC decreased. In contrast, the widths of ICx ITD tuning curves increased more modestly, indicating that tuning resolution alone does not account for behavioral discrimination performance. By computing the Fisher information from ICx neuronal responses, we showed that the average neuronal discriminability predicts behavioral thresholds across BC values. A habituation-based model incorporating BC-dependent changes in tuning width, firing rate, and response variability successfully accounted for both direction and ITD discrimination. These findings support a model in which perceptual acuity is governed by the combined influence of neuronal tuning and variability and provide a unified framework for understanding how midbrain auditory representations underlie adaptive spatial hearing.<b>Significance Statement</b> Determining the relationship between neural coding and perception is a major goal in neuroscience. We studied how barn owls discriminate interaural time differences (ITDs), a primary sound localization cue, when sensory reliability is degraded. Behavioral sensitivity declined sharply with reduced cue reliability, more than expected from changes in neural tuning resolution alone. Instead, behavioral thresholds align with a population-level measure of neural information that accounts for both tuning sharpness and response variability. A computational model suggests that discrimination performance arises from the interaction between neural habituation and degraded signal quality. These findings provide a mechanistic framework for understanding how the brain adapts to noisy environments by integrating reliability into sensory coding.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145245532","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":"Effects of Partial Occlusion on Response Dynamics and Interregional Processing within Primate Superior Temporal Sulcus.","authors":"Anna Bognár,Ghazaleh Ghamkhari Nejad,Rufin Vogels","doi":"10.1523/jneurosci.0979-25.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.0979-25.2025","url":null,"abstract":"Recognizing partially occluded objects is a critical visual function that primates perform with ease, yet the underlying neural mechanisms remain incompletely understood. Previous studies in macaque inferotemporal cortex have reported mixed results on whether occlusion delays and reduces responses to partially occluded objects. To address this, we recorded single-unit activity from body-responsive regions of the middle and anterior Superior Temporal Sulcus (STS) in male macaques while presenting body stimuli with varying levels of occlusion using a dot pattern. Occlusion reduced response strength and increased onset latency in both regions, and even low occlusion levels altered response dynamics by increasing the difference between the response trough and second peak. While body selectivity was preserved, body decoding accuracy declined and was delayed as occlusion increased. In contrast to some prior reports, we found no consistent enhancement of body decoding during the late response phase. By controlling for information loss and clutter introduced by the occluder, we found that reductions in response strength were partly due to the deletion of body features, whereas changes in response dynamics primarily reflected interactions between the occluder and the remaining body features. Occlusion delayed the first but not the second response peak, suggesting distinct mechanisms for these phases. Peak decoding at high occlusion levels emerged later in anterior than middle STS, indicating a feedforward component. However, representational similarity analysis combined with Granger causality suggested enhanced feedback from anterior to middle STS under high occlusion. Together, these results highlight the response dynamics supporting robust recognition under occlusion.Significance statement Recognizing objects under partial occlusion is fundamental to visual perception, yet the underlying neural mechanisms remain unclear. We aimed to clarify previous mixed results concerning the effects of occlusion on ventral stream responses and the contribution of feedback within the Superior Temporal Sulcus (STS) during occlusion. We recorded responses of body-responsive neurons to occluded bodies at two hierarchical levels in the macaque STS. Occlusion consistently reduced response strength and increased onset latency, with even low levels of occlusion altering response dynamics. We found no consistent evidence for enhanced body decoding under occlusion during later phases of the response. Temporal differences between middle and anterior STS representations under occlusion suggest an interplay between feedforward and feedback processes during occluded object recognition.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"80 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145241092","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}
Marta Snapyan,Vlad-Stefan Constantinescu,Armen Saghatelyan,Martin Parent
{"title":"Distinct ultrastructural properties and plasticity of synapses formed by adult-born and early-born interneurons in the mouse olfactory bulb.","authors":"Marta Snapyan,Vlad-Stefan Constantinescu,Armen Saghatelyan,Martin Parent","doi":"10.1523/jneurosci.1358-24.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.1358-24.2025","url":null,"abstract":"The olfactory bulb (OB) is one of the few regions in the adult brain that receives newly generated neuronal precursors throughout the lifespan of animals. These neuronal precursors differentiate into OB interneurons, mostly granule cells (GCs), and integrate into the bulbar network by forming dendro-dendritic reciprocal synapses with OB principal neurons. The ultrastructural properties and plasticity of these synapses and whether they are distinct from those formed by early-born, resident GCs remain unknown. In the present study, we assessed the ultrastructural properties of dendro-dendritic reciprocal synapses formed by either adult-born or resident, early-born GCs with principal neurons in mice of both sexes and studied their plasticity following sensory deprivation and odor learning. The synapses formed by either adult-born or resident, early-born GCs with principal bulbar neurons were undistinguishable in terms of area, diameter, and aspect ratio. In contrast, the synapses formed by adult-born GCs were characterized by a smaller synaptic cleft and a larger density of total and docked synaptic vesicles than synapses formed by resident GCs. Sensory deprivation and odor learning decreased and increased, respectively, the overall density and the number of docked synaptic vesicles in adult-born and resident GCs forming synapses with principal neurons. Our results revealed important differences in the ultrastructural properties of synapses formed by interneurons born at distinct developmental stages and revealed their plasticity in response to sensory deprivation and odor learning.Significance Statement The adult-born neurons in the olfactory bulb play an important role in the bulbar network functioning and odor behavior. In this work, we characterized the ultrastructural properties of synapses formed by adult-born and resident or early-born interneurons with bulbar principal cells and assessed their plasticity following sensory deprivation and odor learning. We revealed marked differences in synapses formed by adult-born interneurons that are characterized by increased density of synaptic vesicles and higher number of docked vesicles as compared to synapses formed by resident, early-born interneurons. We also showed their plasticity following sensory deprivation and odor learning. Our data provide insights for exquisite implication of adult-born interneurons in the odor information processing and odor behavior.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"111 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145215802","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":"Activity deprivation modulates the Shank3/Homer1/mGluR5 signaling pathway to enable synaptic upscaling.","authors":"Andrea A Guerrero, Gina G Turrigiano","doi":"10.1523/JNEUROSCI.0807-25.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.0807-25.2025","url":null,"abstract":"<p><p>Shank3 is an autism spectrum disorder-associated postsynaptic scaffold protein that links glutamate receptors to trafficking and signaling networks within the postsynaptic density. Shank3 is required for synaptic scaling, a form of homeostatic plasticity that bidirectionally modulates post-synaptic strength to stabilize neuronal activity. Shank3 undergoes activity-dependent phosphorylation/dephosphorylation at S1586/S1615, and dephosphorylation at these sites is critical for enabling synaptic upscaling. Here, we probe the molecular machinery downstream of Shank3 dephosphorylation that allows for synaptic upscaling in cultured rat neurons of either sex. We first show that a phosphomimetic mutant of Shank3 has reduced binding ability and interaction with long-form Homer1, a postsynaptic protein also crucial for scaling, and a known binding partner of Shank3. Since metabotropic glutamate receptor 5 (mGluR5) has been shown to associate with Shank3 through long-form Homer1, we manipulated mGluR1 and mGluR5 signaling with either noncompetitive or competitive inhibitors and found that only competitive inhibition (which targets agonist-dependent signaling) impairs synaptic upscaling. Further, we found that mGluR5 activation rescues synaptic upscaling in the presence of phosphomimetic Shank3, and thus is downstream of Shank3 phosphorylation. Finally, we identify signaling pathways downstream of group I mGluRs that are necessary for upscaling. Altogether, these data show that activity-dependent dephosphorylation of Shank3 remodels the Shank3/Homer1/mGluR signaling pathway to favor agonist-dependent mGluR signaling, which is necessary to enable synaptic upscaling. More broadly, because downscaling is thought to require agonist-<i>independent</i> mGluR5 signaling, these findings demonstrate that synaptic up and downscaling rely on distinct functional configurations of the same signaling elements.<b>Significance statement</b> Synaptic scaling is a bidirectional, homeostatic form of synaptic plasticity that allows neural circuits to maintain stable function in the face of experience-dependent or developmental perturbations. Synaptic scaling up requires dephosphorylation of the Autism Spectrum Disorder (ASD)-associated synaptic scaffold protein Shank3, but how this dephosphorylation event enables scaling up was unknown. Here we show that dephosphorylation of Shank3 rearranges interactions between synaptic proteins to drive agonist-dependent signaling through metabotropic glutamate receptors (mGluRs), and that this signaling is necessary for scaling up. These findings show that altered mGluR signaling is downstream of Shank3 during homeostatic plasticity, and raise the possibility that some human Shankopathies impair signaling through this important signaling pathway.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226274","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":"Noise-induced hearing loss enhances Ca<sup>2+</sup>-dependent electrical activity in lateral cochlear efferents.","authors":"Hui Hong 洪卉, Laurence O Trussell","doi":"10.1523/JNEUROSCI.0850-25.2025","DOIUrl":"10.1523/JNEUROSCI.0850-25.2025","url":null,"abstract":"<p><p>Exposure to loud and/or prolonged noise damages cochlea and triggers downstream brain changes, resulting in hearing loss and altered speech comprehension. It remains unclear however whether noise exposure also compromises the cochlear efferent system, a feedback pathway originates in the brain that fine-tunes hearing sensitivity in the cochlea. Recent evidence suggests that lateral olivocochlear (LOC) efferent system supports hearing recovery by sustaining auditory nerve activity for several weeks after acoustic trauma (Sitko et al., 2025); however, the underlying neural mechanisms have not been fully elucidated. To address this gap, we examined the long-term effects of noise-induced hearing loss on the spontaneous action potential (AP) firing pattern in mouse LOC neurons of either sex. Under normal conditions, these neurons display a characteristic burst firing pattern driven by Ca<sup>2+</sup> channel-mediated membrane voltage oscillations. One week following noise exposure, hearing thresholds were significantly elevated, and the duration of AP bursts was increased, as a result of an enhanced Ca<sup>2+</sup> current. Moreover, LOC neurons exhibit Ca<sup>2+</sup>-dependent inactivation (CDI) of Ca<sup>2+</sup> currents - a key process that shapes the duration of voltage oscillations - whose properties were also modified following noise exposure. Interestingly, our data suggest that the interplay between Ca<sup>2+</sup> channel activation, CDI, and outward leak currents is sufficient to sustain the oscillating behavior of LOC neurons. We propose that noise-induced hearing loss increases efferent activity, thereby enhancing the release of neurotransmitters and neuropeptides, which may support long-lasting restoration of sensory coding in the damaged cochlea.<b>Significance Statement</b> while noise-induced hearing loss has been extensively studied in the auditory afferent system, its effects on the efferent system, a key modulator of hearing sensitivity, remain poorly understood. This study addresses this gap by examining Ca<sup>2+</sup> channel-driven spontaneous burst firing in lateral olivocochlear (LOC) neurons, the most numerous auditory efferent neurons. We find that noise exposure selectively increases high-voltage activated Ca<sup>2+</sup> currents, prolonging burst duration and potentially altering intracellular Ca<sup>2+</sup> signaling. These changes persist for more than a week and may significantly affect LOC output to the cochlea. Given the role of Ca<sup>2+</sup> channels in many neurological diseases, this study highlights their underexplored relevance in auditory disorders and the long-term impact of efferent system plasticity on hearing.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214342","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}
David Braun, Lotus Shareef-Trudeau, Swetha Rao, Christine Chesebrough, Julia W Y Kam, Aaron Kucyi
{"title":"Neural sensitivity to the heartbeat is modulated by fluctuations in affective arousal during spontaneous thought.","authors":"David Braun, Lotus Shareef-Trudeau, Swetha Rao, Christine Chesebrough, Julia W Y Kam, Aaron Kucyi","doi":"10.1523/JNEUROSCI.0608-25.2025","DOIUrl":"10.1523/JNEUROSCI.0608-25.2025","url":null,"abstract":"<p><p>Spontaneous thoughts, occupying much of one's awake time in daily life, are often colored by emotional qualities. While spontaneous thoughts have been associated with various neural correlates, the relationship between subjective qualities of ongoing experiences and the brain's sensitivity to bodily signals (i.e., interoception) remains largely unexplored. Given the well-established role of interoception in emotion, clarifying this relationship may elucidate how processes relevant to mental health, such as arousal and anxiety, are regulated. We used EEG and ECG to measure the heartbeat evoked potential (HEP), an index of interoceptive processing, while 51 adult participants (34 male, 20 female) visually fixated on a cross image and let their minds wander freely. At pseudo-random intervals, participants reported their momentary level of arousal. This measure of affective arousal was highly variable within and between individuals but was statistically unrelated to several markers of physiological arousal, including heart rate, heart rate variability, time on task, and EEG alpha power at posterior electrodes. A cluster-based permutation analysis revealed that the HEP amplitude was increased during low relative to high affective arousal in a set of frontal electrodes during the 340 - 356 millisecond window after heartbeat onset. This HEP effect was more pronounced in individuals who reported high, relative to low, levels of trait anxiety. Together, our results offer novel evidence that at varying levels of trait anxiety, the brain differentially modulates sensitivity to bodily signals in coordination with the momentary, spontaneous experience of affective arousal-a mechanism that may operate independently of physiological arousal.<b>Significance Statement</b> Our findings highlight the relationships between spontaneous fluctuations in affective arousal, brain-body interactions, and anxiety, offering new insights into how interoception fluctuates with changes in internal states. By showing that interoceptive processing is heightened during lower affective arousal and that this effect is amplified in individuals with higher trait anxiety, our study suggests the brain adaptively downregulates interoceptive sensitivity in response to fluctuating internal states. These results have implications for understanding how spontaneous thoughts shape interoception and emotion, particularly in clinical contexts where dysregulated interoception is linked to anxiety and mood disorders. More broadly, our work underscores the need to distinguish between different forms of arousal, advancing understanding of the taxonomy and ways of measuring arousal.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214351","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}