Journal of Neuroscience最新文献

{"title":"Theta oscillons in behaving rats.","authors":"M S Zobaer, N Lotfi, C M Domenico, C Hoffman, L Perotti, D Ji, Y Dabaghian","doi":"10.1523/JNEUROSCI.0164-24.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.0164-24.2025","url":null,"abstract":"<p><p>Recently discovered constituents of the brain waves-the <i>oscillons</i>-provide a high-resolution representation of the extracellular field dynamics. Here, we study the most robust, highest-amplitude oscillons recorded in actively behaving male rats, which underlie the traditional <i>θ</i>-waves. The resemblances between <i>θ</i>-oscillons and the conventional <i>θ</i>-waves are manifested primarily at the ballpark level-mean frequencies, mean amplitudes, and bandwidths. In addition, both hippocampal and cortical oscillons exhibit a number of intricate, behavior-attuned, transient properties that suggest a new vantage point for understanding the <i>θ</i>-rhythms' structure, origins and functions. In particular, we demonstrate that oscillons are frequency-modulated waves, with speed-controlled parameters, embedded into a weak noise background. We also use a basic model of neuronal synchronization to contextualize and to interpret the oscillons. The results suggest that the synchronicity levels in physiological networks are fairly low and are modulated by the animal's physiological state.<b>Significance statement</b> Oscillatory extracellular fields modulate neural activity at multiple spatiotemporal scales and hence play major roles in physiology and cognition. Traditionally, these fields' organization is described via harmonic decompositions into <i>θ</i>, <i>γ</i> and other \"brain waves.\" Here we argue that these constructs are only approximations to the physical oscillatory motifs-the oscillons, which represent the actual temporal architecture of synchronized neural dynamics. Focusing on the low-frequency <i>θ</i>-oscillons, we demonstrate correspondences with the traditional <i>θ</i>-waves for averaged, lento-changing characteristics, and discuss several new properties and dynamics that heretofore remained unexplored. Specifically, speed-coupled frequency modulations support oscillatory models of brain wave dynamics, suggesting a novel, \"FM\" perspective on the information exchange in hippocampo-cortical network and linking electrophysiological data to theoretical models of neuronal synchronization.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765620","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":"Characterizing directional dynamics of semantic prediction based on inter-regional temporal generalization.","authors":"Fahimeh Mamashli, Sheraz Khan, Elaheh Hatamimajoumerd, Mainak Jas, Işıl Uluç, Kaisu Lankinen, Jonas Obleser, Angela D Friederici, Burkhard Maess, Jyrki Ahveninen","doi":"10.1523/JNEUROSCI.0230-24.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.0230-24.2025","url":null,"abstract":"<p><p>The event-related potential/field component N400(m) is a widely accepted neural index for semantic prediction. Top-down input from inferior frontal areas to perceptual brain regions is hypothesized to play a key role in generating the N400, but testing this has been challenging due to limitations of causal connectivity estimation. We here provide new evidence for a predictive model of speech comprehension in which IFG activity feeds back to shape subsequent activity in STG/MTG. Magnetoencephalography (MEG) data was obtained from 21 participants (10 men, 11 women) during a classic N400 paradigm where the semantic predictability of a fixed target noun was manipulated in simple German sentences through the preceding verb. To estimate causality, we implemented a novel approach, based on machine learning and temporal generalization, to test the effect of inferior frontal gyrus (IFG) on temporal regions. A support vector machine (SVM) classifier was trained on IFG activity to classify less predicted (LP) and highly predicted (HP) nouns and tested on superior/middle temporal gyri (STG/MTG) activity, time-point by time-point. The reverse procedure was then performed to establish spatiotemporal evidence for or against causality. Significant decoding results were found in our bottom-up model, which were trained at hierarchically lower level areas (STG/MTG) and tested at the hierarchically higher IFG areas. Most interestingly, decoding accuracy also significantly exceeded chance level when the classifier was trained on IFG activity and tested on successive activity in STG/MTG. Our findings indicate dynamic top-down and bottom-up flow of information between IFG and temporal areas when generating semantic predictions.<b>Significance Statement</b> Semantic prediction helps anticipate the meaning of upcoming speech based on contextual information. How frontal and temporal cortices interact to enable this crucial function has remained elusive. We used novel data-driven MEG analyses to infer information flow from lower to higher areas (bottom-up) and vice versa (top-down) during semantic prediction. Using \"earlier\" MEG signals in one area to decode the \"later\" in another, we found that inferior frontal cortices feed predictions back to temporal cortices, to help decipher bottom-up signals going to the opposite direction. Our results provide experimental evidence on how top-down and bottom-up influences interact during language processing.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765618","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":"Dissociable causal roles of dorsolateral prefrontal cortex and primary motor cortex over the course of motor skill development.","authors":"Quynh N Nguyen, Katherine J Michon, Michael Vesia, Taraz G Lee","doi":"10.1523/JNEUROSCI.2015-23.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.2015-23.2025","url":null,"abstract":"<p><p>Established models of motor skill learning posit that early stages of learning are dominated by an attentionally demanding, effortful mode of control supported by associative corticostriatal circuits involving the dorsolateral prefrontal cortex (DLPFC). As skill develops, automatic and \"effortless\" performance coincides with a transition to a reliance on sensorimotor circuits that include primary motor cortex (M1). However, the dynamics of how control evolves during the transition from novice to expert are currently unclear. This lack of clarity is due, in part, to the fact that most motor learning studies comprise a limited number of training sessions and rely on correlative techniques such as neuroimaging. Here, we train human participants (both sexes) on a discrete motor sequencing task over the course of six weeks, followed by an assessment of the causal roles of DLPFC and M1 at varying levels of expertise. We use repetitive transcranial magnetic stimulation to transiently disrupt activity in these regions immediately prior to performance in separate sessions. Our results confirm the dissociable importance of DLPFC and M1 as training progresses. DLPFC stimulation leads to larger behavioral deficits for novice skills than more highly trained skills, while M1 stimulation leads to relatively larger deficits as training progresses. However, our results also reveal that prefrontal disruption causes performance deficits at all levels of training. These findings challenge existing models and indicate an evolving rather than a strictly diminishing role for DLPFC throughout learning.<b>Significance Statement</b> Motor skills involve the sequential chaining of individual actions. For example, playing the piano involves learning to rapidly transition to from one finger press to another. Human neuroimaging studies have shown that primary motor cortex (M1) and dorsolateral prefrontal cortex (DLPFC) support novice motor sequencing skills, but activity in both regions declines over training. This has been interpreted as increased efficiency in M1 and yet a reduction in the involvement of DLPFC as expertise develops. We causally test this assumption by using non-invasive brain stimulation to transiently disrupt cortical activity following extended skill training. Although we confirm dissociable contributions of DLPFC and M1 as training progresses, we show that both regions are necessary for performance regardless of skill level.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765619","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":"Cross-sensitization between binge-eating and -drinking in a novel C57BL/6NJ murine model of disease co-morbidity requires PDE4B activation.","authors":"Lauren E Madory, Ida Kazerani, Edward C Lee, Christopher J E Denning, Estevan Mosqueda De Rosas, Dylan T Nguyen, Elwin Feng, Daniel Kotlyar, Aadithya Kharwa, Melissa A Munn-Chernoff, Camron D Bryant, Karen K Szumlinski","doi":"10.1523/JNEUROSCI.1810-24.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.1810-24.2025","url":null,"abstract":"<p><p>There is a high rate of co-morbidity between binge-eating and binge-drinking behaviors, suggesting a common neuropathology. Recently, <i>phosphodiesterase 4B</i> (<i>PDE4B</i>) was identified as a pleiotropic gene associated with comorbid alcohol use disorder (AUD) and anorexia nervosa with binge-eating in a genome-wide association study, implicating <i>PDE4B</i> as a potential contributor to shared genetic risk between these disorders. To address this possibility, we developed a novel mouse model of co-morbid binge-eating and -drinking in C57BL/6NJ mice in which mice underwent 10 days of binge-eating, followed by 10 days of binge-drinking. Females exhibited cross-sensitization from binge-eating to -drinking, that was apparent on the first day of ethanol access, whereas cross-sensitization emerged in males over multiple trials of binge-drinking. Accordingly immunoblotting of nucleus accumbens tissue indicated a female-selective increase in PDE4B protein expression that was apparent on both the first and last day of binge-drinking in mice with a prior binge-eating history. Acute pretreatment with the selective PDE4B inhibitor A33 (1.0 mg/kg) reduced the expression of cross-sensitization to binge-drinking in females on Day 1 and this effect was maintained during a 5-day A33 treatment regimen. The 5-day A33 treatment regimen also reduced expression of cross-sensitization to binge drinking that had emerged in males over repeated sessions. These results provide preclinical, functional validation of PDE4B as a driver of food-ethanol cross-sensitization in a novel model for binge-eating and -drinking comorbidity and support PDE4B in the shared genetic risk for these behavioral pathologies and as a target for pharmacotherapeutic intervention in comorbid AUD and binge-eating behaviors.<b>Significance statement</b> Binge-eating and -drinking are highly comorbid pathological behaviors that complicate treatment and increase risk of other psychiatric/somatic conditions and mortality. We face a knowledge gap regarding the biological bases of this comorbidity to inform prognosis and treatment-based recovery. Herein, we developed a mouse model of binge-eating/drinking cross-sensitization and showed that 1) prior binge-eating history potentiated subsequent binge ethanol-drinking in both female and male C57BL/6NJ mice, 2) this behavioral cross-sensitization was associated with elevated expression of phosphodiesterase 4B (PDE4B) expression in the nucleus accumbens, and 3) reducing PDE4B activation via systemic pretreatment with a selective inhibitor prevented binge-eating/drinking cross-sensitization in mice of both sexes. Findings implicate enhanced PDE4B signaling in the etiology and treatment of co-morbid binge-eating and -drinking behaviors.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143755536","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":"Stress Management in Athletes: Predictive Effects of Sleep Deprivation-Induced Cognitive Control Changes on Competition Performance.","authors":"Yixuan Song, Yuchen Huang, Yinge Gao, Mingming Zhang, Yongcong Shao, Guangdong Zhou, Hongqiang Sun, Guibin Wang, Tianye Jia, Jie Shi, Yan Sun","doi":"10.1523/JNEUROSCI.1683-24.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.1683-24.2025","url":null,"abstract":"<p><p>Effective stress management is crucial for optimal competition performance in athletes. Sleep deprivation (SD) can elevate physiological and psychological stress, and the SD-changed cognitive and emotion may reflect stress management capability and hold the predictive possibility for athletes' performance in official competitions over some time, however it lacks evidence. Here, we aim to increase stress level for athletes by 24-hour SD and identify the predictive effects of cognitive and emotional changes after 24h-SD on sports performance in official competitions over around 1.5 months. Sixty-five winter sports athletes (35 males) were recruited from college (test set) and professional athletes (validation set) separately. The anxiety and cortisol levels were assessed at baseline, after 24h-SD, and official competition. Athletes underwent cognitive tasks (STROOP, Go/NoGo, Competitive Reaction Time Task, and Iowa Gambling Task) and the event-related potential (ERP) recording at baseline and after SD. Competition performance levels (supernormal, normal and abnormal) were categorized based on a consensus of subjective and objective evaluations. We found anxiety and cortisol levels following 24h-SD were equaled with those observed of official competition. Notably, only the decreased incongruent STROOP response after 24h-SD was negatively associated with performance in official competition. The corresponding P3 component, particularly the delta frequency at central lobe, largely mediated this effect. These findings highlight that the athletes effectively employ cognitive skills to manage stress under acute SD tend to exhibit superior performance.<b>Significance Statement</b> Predictive methods and biomarkers for athletic performance are currently lacking. Our study first confirmed that the changes in attention control after 24h-SD held unique predictive effects for athletes' competition performance over around 1.5 months, and the delta frequency of the P3 EEG component at the central lobe may contribute to it. This study emphasized that athletes can harness additional cognitive resources to enhance stress management, which could lower the risk of abnormal performance in official competitions. Cognitive predictors after SD can assist athletes and coaches in monitoring training state, enhancing stress management to optimize athletic performance, and adjusting athlete participation arrangements.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143755538","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":"The inattentional rhythm in audition.","authors":"Troby Ka-Yan Lui, Eva Boglietti, Benedikt Zoefel","doi":"10.1523/JNEUROSCI.1544-24.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.1544-24.2025","url":null,"abstract":"<p><p>The detection of temporally unpredictable visual targets depends on the preceding phase of alpha oscillations (∼7-12 Hz). In audition, however, such an effect seemed to be absent. Due to the transient nature of its input, the auditory system might be particularly vulnerable to information loss that occurs if relevant information coincides with the low excitability phase of the oscillation. We therefore hypothesised that effects of oscillatory phase in audition will be restored if auditory events are made task-irrelevant and information loss can be tolerated. To this end, we collected electroencephalography (EEG) data from 29 human participants (21F) while they detected pure tones at one sound frequency and ignored others. Confirming our hypothesis, we found that the neural response to task-irrelevant but not to task-relevant tones depends on the pre-stimulus phase of neural oscillations. Alpha oscillations modulated early stages of stimulus processing, whereas theta oscillations (∼3-7 Hz) affected later components, possibly related to distractor inhibition. We also found evidence that alpha oscillations alternate between sound frequencies during divided attention. Together, our results suggest that the efficacy of auditory oscillations depends on the context they operate in, and demonstrate how they can be employed in a system that heavily relies on information unfolding over time.<b>Significance Statement</b> The phase of neural oscillations shapes visual processing, but such an effect seemed absent in the auditory system when confronted with temporally unpredictable events. We here provide evidence that oscillatory mechanisms in audition critically depend on the degree of possible information loss during the oscillation's low excitability phase, possibly reflecting a mechanism to cope with the rapid sensory dynamics that audition is normally exposed to. We reach this conclusion by demonstrating that the processing of task-irrelevant but not task-relevant tones depends on the pre-stimulus phase of neural oscillations during selective attention. During divided attention, cycles of alpha oscillations seemed to alternate between possible acoustic targets similar to what was observed in vision, suggesting an attentional process that generalises across modalities.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143755539","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":"Neural Dynamics in Extrastriate Cortex Underlying False Alarms.","authors":"Bikash Sahoo, Adam C Snyder","doi":"10.1523/JNEUROSCI.1733-24.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.1733-24.2025","url":null,"abstract":"<p><p>The unfolding of neural population activity can be described as a dynamical system. Stability in the latent dynamics that characterize neural population activity has been linked with consistency in animal behavior, such as motor control or value-based decision-making. However, whether similar dynamics characterize perceptual activity and decision-making in the visual cortex is not well understood. To test this, we recorded V4 populations in monkeys engaged in a non-match-to-sample visual change-detection task that required sustained engagement. We measured how the stability in the latent dynamics in V4 might affect monkeys' perceptual behavior. Specifically, we reasoned that unstable sensory neural activity around dynamic attractor boundaries may make animals susceptible to taking incorrect actions when withholding action would have been correct (\"false alarms\"). We made three key discoveries: 1) greater stability was associated with longer trial sequences; 2) false alarm rate decreased (and response times slowed) when neural dynamics were more stable; and, 3) low stability predicted false alarms on a single-trial level, and this relationship depended on the position of the neural activity within the state space, consistent with the latent neural state approaching an attractor boundary. Our results suggest the same outward false alarm behavior can be attributed to two different potential strategies that can be disambiguated by examining neural stability: 1) premeditated false alarms that might lead to greater stability in population dynamics and faster response time and 2) false alarms due to unstable sensory activity consistent with misperception.<b>Significance Statement</b> Many of the primate visual behaviors are recurrent, repetitive, and require sustained engagement. Computational rules guiding the neural dynamics for such behaviors are not well understood. Using a model-free approach to study these neural computations, we discovered that dynamical stability in population activity could explain many facets of visual perceptual behavior. Greater dynamical stability led to fewer lapses in desired behavioral outcomes and made the animal slower to act when such lapses occurred. The degree of stability could nuance whether the lapses in perceptual decisions were premeditated or likely generated due to misperception. These results improve our understanding of the link between the dynamic nature of neural processes and behavior.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143755537","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":"A critical role of Neuroligin 2 C-terminus in OCD and social behavior.","authors":"Saurabh Pandey, Sophia Ostergren, Jun Li, Shixiao Peng, Guohao Wang, Qingjun Tian, Lijin Dong, Wei Lu","doi":"10.1523/JNEUROSCI.1417-24.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.1417-24.2025","url":null,"abstract":"<p><p>Neurodevelopmental and neuropsychiatric disorders such as autism and schizophrenia are devastating brain illnesses that are often associated with deficits in social behaviors. Thus, understanding the molecular mechanisms contributing to the etiology underlying these social defects will be critical in developing therapeutic strategies for these disorders. Here, we have identified a crucial role of carboxyl-terminus (C-tail) of Neuroligin 2 (NL2), a cell adhesion molecule highly enriched at inhibitory synapses, in social behaviors. Indeed, we have found that genetic deletion of NL2 C-tail in mice (StopKI mice) significantly reduces GABAergic synaptic density and inhibitory synaptic transmission in hippocampal CA1 neurons. Importantly, both male and female StopKI mice also manifest elevated obsessive-compulsive disorder (OCD)-like phenotypes. In addition, we have observed impaired social cognition behaviors in these mice that have not been previously observed in NL2 knockout (KO) mice. These data reveal an unappreciated role of the NL2 C-tail in regulating social behaviors and highlights the importance of NL2 C-tail mediated signaling in delineating molecular determinants for neurodevelopmental and neuropsychiatric disorders.<b>Significance Statement</b> Neuroligin 2 (NL2), a cell adhesion molecule enriched at inhibitory synapses, has been implicated in various neuropsychiatric disorders, including anxiety, schizophrenia, and autism. However, the domain-specific contribution of NL2 to the pathogenesis of these disorders remains poorly understood. In this study, we have identified a crucial role for the carboxyl-tail of NL2 in the development of obsessive-compulsive disorder (OCD)-like behavior as well as social behavior. These results highlight the significance of NL2 C-tail-mediated signaling in elucidating the molecular mechanisms underlying neurodevelopmental and neuropsychiatric disorders.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732705","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":"Interindividual Variability In Memory Performance Is Related To Cortico-Thalamic Networks During Memory Encoding And Retrieval.","authors":"Roberta Passiatore, Antonella Lupo, Nicola Sambuco, Linda A Antonucci, Giuseppe Stolfa, Alessandro Bertolino, Teresa Popolizio, Boris Suchan, Giulio Pergola","doi":"10.1523/JNEUROSCI.0975-24.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.0975-24.2025","url":null,"abstract":"<p><p>Encoding new memories relies on functional connections between the medial temporal lobe and the frontoparietal cortices. Multi-scan fMRI showed changes in these functional connections before and after memory encoding, potentially influenced by the thalamus. As different thalamic nuclei are interconnected with distinct cortical networks, we hypothesized that variations in cortico-thalamic recruitment may impact individual memory performance.We used a multi-scan fMRI protocol including a resting-state scan followed by an associative memory task encompassing encoding and retrieval phases, in two independent samples of healthy adults (N₁=29, mean age=26, males=35%; N₂=108; mean age=28, males=52%). Individual activity and functional connectivity were analyzed in the native space to minimize registration bias. By modeling the direct and indirect effects of cortico-thalamic recruitment on memory using Structural Equation Modeling, we showed a positive association between resting-state functional connectivity of the medial thalamic subdivision within the frontoparietal network and memory performance across samples (effect size <i>R²</i> ranging between 0.27 and 0.36; p-values between 0.01 and 4e-05). This direct relationship was mediated by decreased activation of the anterior subdivision during encoding (<i>R²</i> ranging between 0.04 and 0.2; p-values between 0.05 and 0.006) and by increased activation of the medial subdivision during retrieval (<i>R²</i> ranging between 0.04 and 0.2; p-values between 0.05 and 0.004). Moreover, three distinct clusters of individuals displayed different cortico-thalamic patterns across memory phases.We suggest that associative memory encoding relies on the distinct cortico-thalamic pathways involving medial thalamic recruitment and suppression of anterior subdivision to support the successful encoding of new memories.<b>Significance statement</b> Every person is unique in their learning process and related brain functional organization. Prior research has mainly aimed to find shared patterns in how the brain responds to external stimuli, often overlooking individual behavioral differences. We hypothesized that individuals may recruit different neural resources supporting their learning abilities. We investigated whether specific brain configurations are beneficial to individual memory performance. We found that the baseline configuration of select cortico-thalamic networks involving the medial thalamic subdivision supports memory performance via the indirect effects of the anterior thalamic subdivision deactivation and medial activation during the memory task. We propose that cortico-thalamic functioning involving the anterior and medial thalamus underlies interindividual variability in associative memory encoding.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732783","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":"An infralimbic cortex engram encoded during learning attenuates fear generalization.","authors":"Rajani Subramanian, Avery Bauman, Olivia Carpenter, Chris Cho, Gabrielle Coste, Ahona Dam, Kasey Drake, Sara Ehnstrom, Naomi Fitzgerald, Abigail Jenkins, Hannah Koolpe, Runqi Liu, Tamar Paserman, David Petersen, Diego Scala Chavez, Stefano Rozental, Hannah Thompson, Tyler Tsukuda, Sasha Zweig, Megan Gall, Bojana Zupan, Hadley Bergstrom","doi":"10.1523/JNEUROSCI.2120-24.2025","DOIUrl":"10.1523/JNEUROSCI.2120-24.2025","url":null,"abstract":"<p><p>Generalization allows previous experience to adaptively guide behavior when conditions change. The infralimbic (IL) subregion of the ventromedial prefrontal cortex plays a known role in generalization processes, although mechanisms remain unclear. A basic physical unit of memory storage and expression in the brain is a sparse, distributed group of neurons known as an engram. Here, we set out to determine whether an engram established during learning contributes to generalized responses in IL. Generalization was tested in male and female mice by presenting a novel, ambiguous, tone generalization stimulus following Pavlovian defensive (fear) conditioning. The first experiment was designed to test a global role for IL in generalization using chemogenetic manipulations. Results show IL regulates defensive behavior in response to ambiguous stimuli. IL silencing led to a switch in defensive state, from vigilant scanning to generalized freezing, while IL stimulation reduced freezing in favor of scanning. Leveraging activity-dependent \"tagging\" technology (ArcCreER^T2 x eYFP system), an engram, preferentially located in IL Layer 2/3, was associated with the generalization stimulus. Remarkably, in the identical discrete location, fewer reactivated neurons were associated with the generalization stimulus at the remote timepoint (30 days) following learning. When an IL engram established during learning was selectively chemogenetically silenced, freezing increased. Conversely, IL engram stimulation reduced freezing, suggesting attenuated fear generalization. Overall, these data identify a crucial role for IL in suppressing generalized conditioned responses. Further, an IL engram formed during learning functions to later attenuate a conditioned response in the presence of ambiguous threat stimuli.<b>Significance statement</b> Generalization refers to the ability for organisms to use previous experience to guide behavior when environmental conditions change. Despite the immense importance of generalization in adaptive behavior, the precise brain mechanisms remain unknown. Here we identified a small population of neurons, known as an engram, in a discrete region of the frontal cortex that was associated with the expression of generalization related to a threatening situation. When these cells were turned off, generalization increased. When they were turned on, generalization decreased. Considering that over-generalization of threatening stimuli is a known fundamental dimension of both anxiety and post-traumatic stress disorders, these findings have implications not only for our understanding of intrinsic generalization processes but also highly prevalent clinical disorders.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732836","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}