Journal of Neuroscience最新文献

{"title":"Threonine-53 phosphorylation of dopamine transporter dictates kappa opioid receptor mediated locomotor suppression, aversion, and cocaine reward.","authors":"Durairaj Ragu Varman,Sammanda Ramamoorthy,Lankupalle D Jayanthi","doi":"10.1523/jneurosci.0171-25.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.0171-25.2025","url":null,"abstract":"Dynorphin (DYN)/kappa opioid receptor (KOR) activation contributes to aversion, dysphoria, sedation, depression, and enhanced psychostimulant-rewarding effects by inhibiting dopamine (DA) release. The precise neuronal mechanisms underlying these effects remain unclear, limiting the use of KOR agonists in treating mood and substance use disorders. DYN fibers form synapses with DA terminals that express KOR and dopamine transporter (DAT), which is crucial for regulating DA dynamics and related behaviors. Previously, we demonstrated that KOR agonists upregulate DAT activity via ERK1/2 signaling involving phospho-Thr53 DAT (pT53-DAT). However, it remains unclear whether pT53-DAT is involved in KOR-mediated DAT regulation in vivo and whether such a phenomenon contributes to the behavioral effects of KOR agonism. In this study, we utilized male DAT-Ala53 knock-in mice with non-phosphorylatable Ala at position 53 to investigate the role of pT53-DAT in KOR-mediated DAT regulation and its behavioral effects. KOR agonist U69593 increased KOR antagonist-sensitive DAT activity, DAT Vmax, pT53-DAT, and surface expression in WT but not in DAT-Ala53 mice. KOR agonists caused locomotor suppression, conditioned place aversion (CPA), and enhanced cocaine preference (CPP) in WT but not in DAT-Ala53 mice. Conversely, both WT and DAT-Ala53 mice exhibited similar lithium chloride-induced CPA and morphine-induced CPP. These findings provide the first causal evidence that KOR-mediated locomotor suppression, aversive response, and enhancement of cocaine reward manifest through the modulation of DAT activity via DAT-T53 phosphorylation. This suggests that targeting specific DAT-regulatory motif(s) may help develop new KOR-directed therapeutic strategies devoid of adverse effects.Significance Statement Preclinical and clinical research reveal that cocaine use disorder (CUD) affects mesolimbic dopamine neurotransmission, dopamine transporters (DAT), and DA interactions with the dynorphin (DYN)/kappa opioid receptor (KOR) system. The lack of FDA-approved treatments for CUD highlights a significant gap in our understanding of its neurobiology. While KOR ligands have potential as therapies, their effectiveness is often limited by side effects like aversion, dysphoria. and enhancing cocaine reward. Our study demonstrates that phosphorylation of Thr53 motif in DAT is crucial for KOR-mediated aversion, locomotor suppression, and enhancement of cocaine reward. These findings provide the first neurobiological evidence linking DAT-Thr53 phosphorylation to KOR modulation of DA clearance, highlighting its contribution to adverse behavioral outcomes and opening avenues for effective CUD treatments.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"127 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103741","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":"Modulation of dopamine neurons alters behavior and event encoding in the nucleus accumbens during Pavlovian conditioning.","authors":"Ethan W Herring,Kira B Lear,Sandford Zeng,Elin F B McLaughlin,Tulasi Syamala,Eesha D Patel,Kyle Duffer,Sara E Morrison","doi":"10.1523/jneurosci.0061-25.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.0061-25.2025","url":null,"abstract":"When a cue is located away from its associated reward, some animals will learn to approach the site of reward (goal-tracking behavior) while others will approach the cue (sign-tracking behavior). The acquisition of sign tracking, but not goal tracking, is dependent on dopamine in the nucleus accumbens (NAc), and we have previously demonstrated that reward-evoked activity in the NAc core may reflect different patterns of dopamine release in sign tracker vs. goal tracker individuals. However, a causal relationship among dopamine release, NAc activity, and sign tracking has not been established. Using male and female TH::Cre rats, we expressed inhibitory or excitatory opsins in dopamine neurons of the ventral tegmental area (VTA) and examined the impact of optical manipulation of dopamine neurons on behavior and concurrent NAc neuronal activity. We found that inhibition of VTA dopamine neurons at the time of reward suppressed the acquisition of sign-tracking, but not goal-tracking, behavior. On the other hand, stimulation of dopamine neurons did not alter the acquisition of sign tracking; however, cessation of stimulation impeded further acquisition of sign tracking. Finally, both inhibition and stimulation of VTA dopamine neurons rapidly modulated activity in a subset of NAc neurons and led to changes in cue- and reward-related activity across sessions. Overall, these findings support the ideas that sign tracking and goal tracking are the products of two different learning processes - one dopamine-dependent and one not - and that the impact of VTA dopamine on sign tracking may be mediated by activity in the NAc core.Significance Statement During Pavlovian reward conditioning, activity patterns in the nucleus accumbens (NAc) core appear to reflect differences in dopamine release between sign trackers - individuals who tend to approach reward-paired cues - and goal trackers, who tend to approach the site of reward. Here, we use optogenetics to inhibit or stimulate dopamine neurons at the time of reward during learning. We show that inhibition suppresses the acquisition of sign-tracking behavior but not goal-tracking behavior; meanwhile, stimulation has no overt effect, but cessation of stimulation suppresses further acquisition of sign tracking, but not goal tracking. Finally, by recording from individual neurons concurrent with optical stimulation/inhibition, we show that these effects may be mediated by a small subset of neurons in the NAc core.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"38 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103745","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":"Opioid Receptors Modulate Inhibition within the Prefrontal Cortex Through Dissociable Cellular and Molecular Mechanisms.","authors":"Rebecca H Cole, Marie-Charlotte Allichon, Max E Joffe","doi":"10.1523/JNEUROSCI.1963-24.2025","DOIUrl":"10.1523/JNEUROSCI.1963-24.2025","url":null,"abstract":"<p><p>Aberrant signaling within cortical inhibitory microcircuits has been identified as a common signature of neuropsychiatric disorders. Interneuron (IN) activity is precisely regulated by neuromodulatory systems that evoke widespread changes in synaptic transmission and principal cell output. Cortical interneurons express high levels of opioid receptors, positioning opioid signaling as a critical regulator of inhibitory transmission. However, we lack a complete understanding of how classical opioid receptor systems regulate prefrontal cortex (PFC) microcircuitry. Here, we combine whole-cell patch-clamp electrophysiology, optogenetics, and viral tools to provide an extensive characterization of how the Mu opioid receptor (MOR), Delta opioid receptor (DOR), and Kappa opioid receptor (KOR) regulate inhibitory transmission in male and female mice. We show that across these receptor systems, DOR activation is more effective at suppressing spontaneous inhibitory transmission in layer 2/3 of the prelimbic PFC, while MOR causes a greater acute suppression of electrically-evoked GABA release, and KOR plays a minor role in inhibitory transmission. Cell type-specific optogenetics revealed that MOR and DOR differentially regulate inhibitory transmission from parvalbumin, somatostatin, cholecystokinin, and vasoactive intestinal peptide-expressing INs. Finally, we demonstrate that DOR regulates inhibitory transmission through simultaneous pre- and postsynaptic modifications to IN physiology, whereas MOR function varies between somato-dendritic or presynaptic signaling depending on cell type.<b>Significance Statement</b> The endogenous opioid system regulates behaviors that rely on prefrontal cortex (PFC) function. Previous studies have described opioid receptor expression within cortical GABAergic interneurons, but a detailed understanding of how the Mu (MOR), Delta (DOR), and Kappa opioid receptor (KOR) regulate different interneuron subtypes and microcircuits has not been reported. We use whole-cell patch-clamp electrophysiology, genetically engineered mice, and optogenetics to assess MOR, DOR, and KOR regulation of PFC inhibitory transmission, demonstrating that MOR and DOR inhibition of interneurons display qualitative and quantitative variation across GABAergic circuits within mouse prelimbic PFC.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112626","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":"Atypical cadherin FAT2 is required for synaptic integrity and motor behaviors.","authors":"Xiankun Wang,Yadi Pu,Jifei Miao,Li Xie,Liangyu Guan,Yongfei Cui,Jun Wang,Liming Qin,Ying Han,Markus Wöhr,Bo Zhang","doi":"10.1523/jneurosci.2345-24.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.2345-24.2025","url":null,"abstract":"In humans, mutations or deletions of atypical FAT cadherin genes are linked to autism spectrum disorder and cerebellar ataxia. However, their large genomic size and the enormous size of their encoded proteins have hampered functional studies, leaving the roles of FAT cadherins poorly understood. To address this gap, we investigated FAT2-an atypical cadherin selectively expressed in cerebellar granule cells-in murine cerebellar function. We demonstrate that FAT2 directly binds Cbln1, a secreted molecule essential for synapse formation and plasticity at Purkinje cell synapses. Furthermore, Fat2 deletion mice of both sexes selectively weakened the synaptic strength of parallel fiber synapses in the cerebellum and impaired motor behaviors. These findings reveal that FAT2 is indispensable for motor behaviors, likely through regulating Cbln1-dependent synaptic integrity.Significance Statement Abnormal motor behavior is a hallmark of many neurological and psychiatric disorders and a common symptom across numerous diseases. Growing evidence highlights the critical role of the motor system in elucidating the pathophysiology and treatment of mental disorders. Digging behavior-a movement characterized by forefeet scratching and/or hindfeet substrate kicking-is poorly understood at the genetic level. Here, we identify FAT Atypical Cadherin 2 (FAT2) as a binding partner of Cbln1, a synaptic organizer for cerebellar parallel fiber synapses. We demonstrate that deletion of cerebellar granule cell FAT2 impairs synaptic integrity and motor behaviors. These findings establish FAT2 as essential for synaptic integrity and the execution of fine motor and digging behaviors.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"44 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103699","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":"Regional Excitatory-Inhibitory Balance Relates to Self-Reference Effect on Recollection via the Precuneus/Posterior Cingulate Cortex-Medial Prefrontal Cortex Connectivity.","authors":"Ying He,Hilary Sweatman,Alice R Thomson,Zeus Garcia Tabuenca,Nicolaas A Puts,Xiaoqian J Chai","doi":"10.1523/jneurosci.2343-24.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.2343-24.2025","url":null,"abstract":"Self-related representation can enhance perception and memory -a phenomenon known as the self-referential effect (SRE). While SRE has been linked to the activation of the default mode network (DMN), including the precuneus/posterior cingulate cortex (Pcu/PCC) and the medial prefrontal cortex (mPFC), the underlying neurochemical processes of DMN activations remain unclear. The balance of excitation and inhibition (E/I balance) within brain circuits is crucial for cognition and may play a role in the SRE. We examine whether the ratio of glutamate/glutamine (Glx) to γ-aminobutyric acid (GABA) concentrations, measured by 1H-Magnetic Resonance Spectroscopy (1H-MRS) as a proxy measure for E/I balance, is associated with DMN neural processes involved in self-referential encoding. Fifty-four healthy participants aged 7-35 (25 female) underwent MRS to measure levels of Glx and GABA in Pcu/PCC, and completed a functional Magnetic Resonance Imaging (fMRI) scan during an encoding task that involved self-referential and semantic judgments. We found that the self-related condition led to better subsequent memory and greater activation in the Pcu/PCC compared to the semantic condition. Activations in the Pcu/PCC was positively correlated with the Glx/GABA+ ratio. Task-dependent functional connectivity analysis revealed that connectivity between the Pcu/PCC and medial prefrontal cortex (mPFC) was positively associated with both the Glx/GABA+ ratio and the SRE effect on recollection accuracy. Furthermore, mediation analysis showed that a higher Glx/GABA+ ratio correlated with better SRE on memory recollection through increased Pcu/PCC-mPFC connectivity. Our study provides valuable insights into how neurochemical activity is associated with self-related cognition via functional connectivity of large-scale brain networks.Significance Statement Self-related representation can enhance perception and memory - a phenomenon known as the self-referential effect (SRE). While SRE has been linked to the activation of the default mode network (DMN), the underlying neurochemical processes remain unclear. Our study found that SRE was associated with the ratio of glutamate/glutamine (Glx) and γ-aminobutyric acid (GABA) concentrations, a proxy measure of excitatory/inhibitory balance, through functional connectivity between key nodes of the DMN. These findings indicate the critical role of excitatory/inhibitory balance in self-related processes, which may provide new insights into psychiatric disorders characterized by impaired self-awareness.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"40 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103744","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":"Anchoring functional connectivity to individual sulcal morphology yields insights in a pediatric study of reasoning.","authors":"Suvi Häkkinen, Willa I Voorhies, Ethan H Willbrand, Yi-Heng Tsai, Thomas Gagnant, Jewelia K Yao, Kevin S Weiner, Silvia A Bunge","doi":"10.1523/JNEUROSCI.0726-24.2025","DOIUrl":"10.1523/JNEUROSCI.0726-24.2025","url":null,"abstract":"<p><p>A salient neuroanatomical feature of the human brain is its pronounced cortical folding, and there is mounting evidence that sulcal morphology is relevant to functional brain architecture and cognition. However, our understanding of the relationships between sulcal anatomy, brain activity, and behavior is still in its infancy. We previously found that the depth of three small, shallow sulci in lateral prefrontal cortex (LPFC) was linked to reasoning performance during development (Voorhies et al., 2021). These findings beg the question: what is the linking mechanism between sulcal morphology and cognition? Here, we investigated functional connectivity among sulci in LPFC and lateral parietal cortex (LPC) in participants from the same sample as our previous study. We leveraged manual parcellations (21 sulci/hemisphere, total of 1806) and functional magnetic resonance (fMRI) data from a reasoning task from 43 participants aged 7-18 years (20 female). We conducted clustering and classification analyses of individual-level functional connectivity among sulci. Broadly, we found that 1) the connectivity patterns of individual sulci could be differentiated - and more accurately than rotated sulcal labels equated for size and shape; 2) sulcal connectivity did not consistently correspond with that of probabilistic labels or large-scale networks; 3) sulci clustered together into groups with similar patterns, not dictated by spatial proximity; and 4) across individuals, greater depth was associated with higher network centrality for several sulci under investigation. These results illustrate how sulcal morphology can be relevant for functional connectivity, and provide proof of concept that using sulci to define an individual coordinate space for functional connectomes is a promising future direction.<b>Significance Statement</b> A salient, and behaviorally relevant, feature of the human brain is its pronounced cortical folding. However, the links between sulcal anatomy and brain function are still poorly understood - particularly for small, shallow, individually variable sulci in association cortices. Here, focusing on the functional connectivity between individually defined sulci in lateral prefrontal and parietal regions in a pediatric sample, we demonstrate for the first time a link between functional network centrality and sulcal morphology. This result, along with control analyses, provide proof of concept that defining functional brain networks in relation to sulcal anatomy is a promising way forward.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102920","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":"Specializations in amygdalar and hippocampal innervation of the primate nucleus accumbens shell.","authors":"L G Marshall,H Barbas","doi":"10.1523/jneurosci.2425-24.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.2425-24.2025","url":null,"abstract":"The Nucleus accumbens (NAc) is critical to goal-directed behaviors as the main input structure for limbic pathways to the basal ganglia. The NAc shell is composed of inhibitory projection neurons that receive robust glutamatergic innervation from both the hippocampus and amygdala. In view of primate-specific changes in the neural composition of the NAc, it is still unclear how its circuits are organized in primates. We used a system-to-synapse approach to characterize amygdalar and hippocampal pathway distribution, innervation patterns, and synaptic characteristics in the NAc shell of rhesus monkeys (Macaca mulatta) of both sexes. Key findings showed that both the amygdalar and hippocampal pathways disproportionately innervated NAc shell interneurons relative to their population sizes, assessed via confocal systems' analysis and at the synaptic level with electron microscopy. The synaptic features associated with the two pathways were distinct. The amygdalar projection was denser, with larger boutons that more often contained mitochondria than the hippocampal projection. The hippocampal pathway had larger postsynaptic densities and more frequently formed perforated synapses, which are features associated with high synaptic efficacy. In addition, hippocampal boutons more frequently formed multiple synapses, often with one projection neuron and one interneuron. These interactions with the NAc shell suggest distinct mechanisms for the processing of affective signaling from the amygdala and contextual information from the hippocampus.Significance Statement The nucleus accumbens (NAc) is a key structure for motivated behavior; it receives dense pathways from the amygdala, associated with emotional significance, and the hippocampus, associated with context. In the NAc shell, both pathways disproportionately innervated interneurons, relative to their population size. The amygdalar boutons were somewhat larger and enriched with mitochondria, associated with sustained activity. Hippocampal terminations formed larger synapses and were more often multi-synaptic, suggesting high synaptic efficacy. These patterns diverge from previously described rodent circuit patterns. The findings suggest that internal emotional state and environmental cues related to context differentially affect circuits underlying goal-directed behavior in the NAc shell.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"42 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065810","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":"Chemogenetic disruption of monkey perirhinal neurons projecting to rostromedial caudate impairs associative learning.","authors":"Wenliang Wang,Mark A G Eldridge,Tsuyoshi Setogawa,Spencer Webster-Bass,Nanami Miyazaki,Jonah E Pearl,Jeih-San Liow,Walter Lerchner,Bing Li,Janita N Turchi,Sanjay Telu,Sridhar Goud Nerella,Phelix Rodriguez,Robert B Innis,Victor W Pike,Bruno B Averbeck,Barry J Richmond","doi":"10.1523/jneurosci.0491-25.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.0491-25.2025","url":null,"abstract":"Primates, including humans, use stimulus-reward associations to guide foraging. We previously showed that both rhinal cortex (Rh) and rostromedial caudate (rmCD) of rhesus monkeys play causal roles in assigning value to visual stimuli. Layer 5 neurons in Rh project to rmCD. Here, we reversibly interrupted this layer 5 connection in two male monkeys by combining a unilateral Rh lesion with contralateral expression of an inhibitory DREADD delivered using a retrograde lentivirus (FuG-E) injected into rmCD. Interruption of projection neurons from Rh to rmCD had little effect on already learned stimulus-reward associations but impaired the learning of new associations. The learning impairment appeared when the projection neurons from perirhinal cortex (PRh) to rmCD were silenced using microinjections of deschloroclozapine (DCZ) into PRh. The pathway-specific silencing led to a significant deficit in learning new stimulus-reward associations. These results suggest that the learning, but not retrieval, of visual stimulus-reward associations involves projection neurons from PRh to rmCD.Significance Statement Primates use stimulus-reward associations to guide foraging. Both Rh and rmCD play a causal role in visual-stimulus-reward associations in non-human primates. There is a strong anatomical projection from Rh to rmCD. This connection was reversibly interrupted by combining a unilateral Rh lesion with contralateral expression of an inhibitory DREADD via a retrograde lentivirus (FuG-E) injected into rmCD. Interruption of this connection had little effect on already learned stimulus-reward associations but impaired the learning of new associations. We further localized the source of this learning impairment to neurons projecting to rmCD from the Rh, i.e., PRh. Our findings emphasize the significance of this circuit in adaptive behavior and indicate that learning and retrieval depend on different neural pathways.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"103 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065811","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":"Electrophysiological Correlates of Lucid Dreaming: Sensor and Source Level Signatures","authors":"Çağatay Demirel, Jarrod Gott, Kristoffer Appel, Katharina Lüth, Christian Fischer, Cecilia Raffaelli, Britta Westner, Xinlin Wang, Zsófia Zavecz, Axel Steiger, Daniel Erlacher, Stephen LaBerge, Sérgio Mota-Rolim, Sidarta Ribeiro, Marcel Zeising, Nico Adelhöfer, Martin Dresler","doi":"10.1523/jneurosci.2237-24.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.2237-24.2025","url":null,"abstract":"<p>Lucid dreaming (LD) is a state of conscious awareness of the ongoing oneiric state, predominantly linked to REM sleep. Progress in understanding its neurobiological basis has been hindered by small sample sizes, diverse EEG setups, and artifacts like saccadic eye movements. To address these challenges in characterizing the electrophysiological correlates of LD, we introduced an adaptive multistage preprocessing pipeline, applied to human data (male and female) pooled across laboratories, allowing us to explore sensor- and source-level markers of LD. We observed that, while sensor-level differences between LD and nonlucid REM sleep were minimal, mixed-frequency analysis revealed broad low alpha to gamma power reductions during LD compared with wakefulness. Source-level analyses showed significant beta power (12&ndash;30&nbsp;Hz) reductions in right central and parietal areas, including the temporoparietal junction, during LD. Moreover, functional connectivity in the alpha band (8&ndash;12&nbsp;Hz) increased during LD compared with nonlucid REM sleep. During initial LD eye signaling compared with the baseline, source-level gamma1 power (30&ndash;36&nbsp;Hz) increased in right temporo-occipital regions, including the right precuneus. Finally, functional connectivity analysis revealed increased interhemispheric and inter-regional gamma1 connectivity during LD, reflecting widespread network engagement. These results suggest that distinct source-level power and connectivity patterns characterize the dynamic neural processes underlying LD, including shifts in network communication and regional activation that may underlie the specific changes in perception, memory processing, self-awareness, and cognitive control. Taken together, these findings illuminate the electrophysiological correlates of LD, laying the groundwork for decoding the mechanisms of this intriguing state of consciousness.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"4 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945870","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":"Universal Coding for Uncertainty?","authors":"Chun-Kit Law, Jocelyn Yuen Lam To","doi":"10.1523/JNEUROSCI.2023-24.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.2023-24.2025","url":null,"abstract":"","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"45 20","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12079748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081570","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}