Journal of Neuroscience最新文献

筛选
英文 中文
Tracking neural correlates of contextualized meanings with representational similarity analysis.
IF 4.4 2区 医学
Journal of Neuroscience Pub Date : 2025-03-27 DOI: 10.1523/JNEUROSCI.0409-24.2025
Aline-Priscillia Messi, Liina Pylkkanen
{"title":"Tracking neural correlates of contextualized meanings with representational similarity analysis.","authors":"Aline-Priscillia Messi, Liina Pylkkanen","doi":"10.1523/JNEUROSCI.0409-24.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.0409-24.2025","url":null,"abstract":"<p><p>Although it is uncontroversial that word meanings shift depending on their context, our understanding of contextualized lexical meaning remains poor. How is a contextualized semantic space organized? In this MEG study (27 human participants, 16 women, 10 men, 1 non-binary), we manipulated the semantic and syntactic contexts of word forms to query the organization of this space. All wordforms were noun/verb ambiguous and varied in the semantic distance between their noun and verb uses: unambiguous stems, polysemes with distinct but related meanings, and homonyms with completely unrelated meanings. The senses of each stem were disambiguated by a unique discourse sentence and the items were placed in syntactic contexts of varying sizes. Univariate results characterized syntactic context as a bilateral and distributed effect. A multivariate Representational Similarity Analysis correlated one-hot models of the categorical factors as well as contextualized embedding-based models with MEG activity. Of all models representing ambiguity, only a model differentiating between syntactic categories across contexts correlated with the brain. An All-Embeddings model, where each contextualized word had a distinct representation, explained distributed neural activity across the left hemisphere. Finally, a Syntactic Context model and Within-Context-Stem model were significant in left occipito-parietal regions. While the noun vs. verb contrast affected neural signals robustly, we saw no evidence of the homonym-polyseme-unambiguous contrast, over and above the evidence for fully itemized representations. These findings suggest that in contexts devoid of ambiguity, the neural representation of a word is mainly shaped by its syntactic category and its contextually informed, unique semantic representation.<b>Significance statement</b> A word's context can define its meaning. Context is an integral part of understanding language, yet the organization of the semantic space formed by words in context remains unclear. We used magnetoencephalography (MEG) to investigate the dynamic interaction between contextualized semantic representations, syntactic categories, ambiguity and local syntactic contexts. We find a left-lateralized network encoding a semantic space where each contextualized instance of a word has a distinct neural representation, while syntactic category had a broad bilateral representation. Our study provides a link between naturalistic multivariate studies of item/word-level semantic processing and more traditional controlled factorial investigations of lexical meaning. These findings enrich our understanding of the neural underpinnings of words in context and highlights the role of syntactic context.</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":"143732792","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}
引用次数: 0
Hemifield Specificity of Attention Response Functions During Multiple Object Tracking.
IF 4.4 2区 医学
Journal of Neuroscience Pub Date : 2025-03-27 DOI: 10.1523/JNEUROSCI.1340-24.2025
Marvin R Maechler, Eunhye Choe, Patrick Cavanagh, Peter J Kohler, Peter U Tse
{"title":"Hemifield Specificity of Attention Response Functions During Multiple Object Tracking.","authors":"Marvin R Maechler, Eunhye Choe, Patrick Cavanagh, Peter J Kohler, Peter U Tse","doi":"10.1523/JNEUROSCI.1340-24.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.1340-24.2025","url":null,"abstract":"<p><p>The difficulty of tracking multiple moving objects among identical distractors increases with the number of tracked targets. Previous research has shown that the number of targets tracked (i.e., load) modulates activity in brain areas related to visuospatial attention, giving rise to so-called \"Attention Response Functions\" (ARFs). While the hemifield/hemispheric effects of spatial attention (e.g., hemispatial neglect, hemifield capacity limits) are well described, it had not previously been tested whether a hemispheric or hemifield imbalance exists among ARFs. By recording BOLD activity from human brains (n=19, female and male) in a multiple object tracking paradigm, we show that the number of tracked objects modulates activity in a large network of areas bilaterally. A significant effect of contralateral load was found in earlier areas throughout the dorsal and ventral visual streams, while the effects of ipsilateral load emerged in later areas. Both contra- and ipsilateral load significantly influenced activity in the parietal and frontal lobes, specifically the dorsal attention network. In addition, some brain regions in the occipital lobe were significantly more sensitive to contralateral than ipsilateral load. Our results are consistent with findings showing that a diverse set of brain areas contributes to tracking multiple targets. In particular, we extend the canonical view of load-based ARFs to include hemifield bias. Given the hemifield-specific nature of speed and capacity limits to multiple object tracking, we conjecture that areas that show a strong hemifield preference may impose a bottleneck on processing that results in limits on the capacity and speed of tracking.<b>Significance Statement</b> We investigated how attentional effort impacts brain activity. Effort (the number of targets in a multiple object tracking task) parametrically drives activity in the attention system. Our findings reveal brain areas where effort driven increases in activity are dependent on the visual hemifield where targets are tracked. We show that the load-dependent responses differ between earlier visual areas, which prefer targets on the contralateral side, and later areas that respond to targets anywhere in the visual field. This research challenges previous explanations of hemispatial neglect and enhances our understanding of how the brain manages spatial attention and mental effort. Additionally, we identify regions that might be the source of hemifield-specific capacity limits in attentional tracking.</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":"143732855","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}
引用次数: 0
Pmp2+ Schwann Cells Maintain the Survival of Large-Caliber Motor Axons.
IF 4.4 2区 医学
Journal of Neuroscience Pub Date : 2025-03-26 DOI: 10.1523/JNEUROSCI.1362-24.2025
Mikolaj M Kozlowski, Amy Strickland, Ana Morales Benitez, Robert E Schmidt, A Joseph Bloom, Jeffrey Milbrandt, Aaron DiAntonio
{"title":"Pmp2+ Schwann Cells Maintain the Survival of Large-Caliber Motor Axons.","authors":"Mikolaj M Kozlowski, Amy Strickland, Ana Morales Benitez, Robert E Schmidt, A Joseph Bloom, Jeffrey Milbrandt, Aaron DiAntonio","doi":"10.1523/JNEUROSCI.1362-24.2025","DOIUrl":"10.1523/JNEUROSCI.1362-24.2025","url":null,"abstract":"<p><p>Neurodegenerative diseases of both the central and peripheral nervous system are characterized by selective neuronal vulnerability, i.e., pathology that affects particular types of neurons. While much of this cell type selectivity may be driven by intrinsic differences among the neuron subpopulations, neuron-extrinsic mechanisms such as the selective malfunction of glial support cells may also play a role. Recently, we identified a population of Schwann cells (SCs) expressing <i>Adamtsl1</i>, <i>Cldn14</i>, and <i>Pmp2</i> (a.k.a. PMP2+ SCs) that preferentially myelinate large-caliber motor axons. PMP2+ SCs are decreased in both amyotrophic lateral sclerosis (ALS) model mice and ALS patient nerves. Thus, PMP2+ SC dysfunction could contribute to motor-selective neuropathies. We engineered a tamoxifen-inducible Pmp2-CreERT2 mouse and expressed diphtheria toxin in PMP2+ SCs to assess the consequences of ablating this SC subtype in male and female mice. Loss of PMP2+ SCs led to significant loss of large-caliber motor axons with concomitant behavioral, electrophysiological, and ultrastructural defects. Subsequent withdrawal of tamoxifen restored both PMP2+ SCs and large-caliber motor axons and improved behavioral and electrophysiological readouts. Together, our findings highlight that the survival of large-caliber motor axons relies on PMP2+ SCs, demonstrating that malfunction of a specific SC subtype can lead to selective neuronal vulnerability.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143068540","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}
引用次数: 0
Object and Task Features Influence Visual and Sensorimotor Integration in Grasping Tasks.
IF 4.4 2区 医学
Journal of Neuroscience Pub Date : 2025-03-26 DOI: 10.1523/JNEUROSCI.1976-24.2025
Rana Abdelhalim
{"title":"Object and Task Features Influence Visual and Sensorimotor Integration in Grasping Tasks.","authors":"Rana Abdelhalim","doi":"10.1523/JNEUROSCI.1976-24.2025","DOIUrl":"10.1523/JNEUROSCI.1976-24.2025","url":null,"abstract":"","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"45 13","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732844","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}
引用次数: 0
Kölliker's Organ Functions as a Developmental Hub in Mouse Cochlea Regulating Spiral Limbus and Tectorial Membrane Development.
IF 4.4 2区 医学
Journal of Neuroscience Pub Date : 2025-03-26 DOI: 10.1523/JNEUROSCI.0721-24.2025
Hongji Zhang, Timothy Papiernik, Selena Tian, Amal Yaghmour, Ahmad Alzein, James Benjamin Lennon, Rahul Maini, Xiaodong Tan, Ava Niazi, Joosang Park, Sungjin Park, Claus-Peter Richter, Michael Ebeid
{"title":"Kölliker's Organ Functions as a Developmental Hub in Mouse Cochlea Regulating Spiral Limbus and Tectorial Membrane Development.","authors":"Hongji Zhang, Timothy Papiernik, Selena Tian, Amal Yaghmour, Ahmad Alzein, James Benjamin Lennon, Rahul Maini, Xiaodong Tan, Ava Niazi, Joosang Park, Sungjin Park, Claus-Peter Richter, Michael Ebeid","doi":"10.1523/JNEUROSCI.0721-24.2025","DOIUrl":"10.1523/JNEUROSCI.0721-24.2025","url":null,"abstract":"<p><p>Kölliker's organ is a transient developmental structure in the mouse cochlea that undergoes significant remodeling postnatally. Utilizing an epithelial-specific conditional deletion mouse model of <i>Prdm16</i> (marker and regulator of Kölliker's organ), we show that <i>Prdm16</i> is required for interdental cell development, and thereby the development of the limbal domain of the tectorial membrane and its medial anchorage to the spiral limbus. Additionally, we show that Kölliker's organ is involved in normal tectorial membrane collagen fibril development and maturation. Interestingly, mesenchymal cells of the spiral limbus underneath <i>Prdm16</i>-deficient Kölliker's organ failed to produce interstitial matrix proteins, resulting in a hypoplastic and truncated spiral limbus, indicating a non-cell autonomous role of <i>Prdm16</i> in regulating spiral mesenchymal matrix development. Single-cell RNA sequencing identified differentially expressed genes in <i>Prdm16</i>-deficient Kölliker's organ suggesting a role for connective tissue growth factor (CTGF) downstream <i>Prdm16</i> in epithelial-mesenchymal signaling involved in spiral limbus matrix deposition. <i>Prdm16</i>-deficient mice showed a hearing deficit, as indicated by elevated auditory brainstem response thresholds at most frequencies, consistent with the cochlear structural defects. Both sexes were studied. This work establishes <i>Prdm16</i> as a deafness gene in mice through its role in regulating Kölliker's organ development. Such understanding recognizes Kölliker's organ as a developmental hub regulating multiple surrounding cochlear structures.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257326","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}
引用次数: 0
Neuroendocrine Control of Synaptic Transmission by PHAC-1 in C. elegans.
IF 4.4 2区 医学
Journal of Neuroscience Pub Date : 2025-03-26 DOI: 10.1523/JNEUROSCI.1767-23.2024
Aikaterini Stratigi, Miguel Soler-García, Mia Krout, Shikha Shukla, Mario De Bono, Janet E Richmond, Patrick Laurent
{"title":"Neuroendocrine Control of Synaptic Transmission by PHAC-1 in <i>C. elegans</i>.","authors":"Aikaterini Stratigi, Miguel Soler-García, Mia Krout, Shikha Shukla, Mario De Bono, Janet E Richmond, Patrick Laurent","doi":"10.1523/JNEUROSCI.1767-23.2024","DOIUrl":"10.1523/JNEUROSCI.1767-23.2024","url":null,"abstract":"<p><p>A dynamic interplay between fast synaptic signals and slower neuromodulatory signals controls the excitatory/inhibitory (E/I) balance within neuronal circuits. The mechanisms by which neuropeptide signaling is regulated to maintain E/I balance remain uncertain. We designed a genetic screen to isolate genes involved in the peptidergic maintenance of the E/I balance in the <i>C. elegans</i> motor circuit. This screen identified the <i>C. elegans</i> orthologs of the presynaptic phosphoprotein synapsin (<i>snn-1</i>) and the protein phosphatase 1 (PP1) regulatory subunit PHACTR1 (<i>phac-1</i>). We demonstrate that both <i>phac-1</i> and <i>snn-1</i> alter the motor behavior of <i>C. elegans</i>, and genetic interactions suggest that SNN-1 contributes to PP1-PHAC-1 holoenzyme signaling. De novo variants of human PHACTR1, associated with early-onset epilepsies [developmental and epileptic encephalopathy 70 (DEE70)], when expressed in <i>C. elegans</i> resulted in constitutive PP1-PHAC-1 holoenzyme activity. Unregulated PP1-PHAC-1 signaling alters the synapsin and actin cytoskeleton and increases neuropeptide release by cholinergic motor neurons, which secondarily affects the presynaptic vesicle cycle. Together, these results clarify the dominant mechanisms of action of the DEE70 alleles and suggest that altered neuropeptide release may alter E/I balance in DEE70.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371423","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}
引用次数: 0
TIGAR Suppresses ER Stress-Induced Neuronal Injury through Targeting ATF4 Signaling in Cerebral Ischemia/Reperfusion.
IF 4.4 2区 医学
Journal of Neuroscience Pub Date : 2025-03-26 DOI: 10.1523/JNEUROSCI.1406-24.2025
Lei Chen, Jie Tang, Xue-Qing Liu, Qi-Qi Li, Jia-Ying Li, Yan-Yan Li, Wen-Hua Zheng, Zheng-Hong Qin, Rui Sheng
{"title":"TIGAR Suppresses ER Stress-Induced Neuronal Injury through Targeting ATF4 Signaling in Cerebral Ischemia/Reperfusion.","authors":"Lei Chen, Jie Tang, Xue-Qing Liu, Qi-Qi Li, Jia-Ying Li, Yan-Yan Li, Wen-Hua Zheng, Zheng-Hong Qin, Rui Sheng","doi":"10.1523/JNEUROSCI.1406-24.2025","DOIUrl":"10.1523/JNEUROSCI.1406-24.2025","url":null,"abstract":"<p><p>Endoplasmic reticulum (ER) stress is crucial in cerebral ischemia/reperfusion injury by triggering cellular apoptosis and exacerbating neuronal damage. This study elucidates the dynamics of TP53-induced glycolysis and apoptosis regulator (TIGAR) translocation and its role in regulating neural fate during cerebral ischemia-induced ER stress, specifically in male mice. We found enhanced nuclear localization of TIGAR in neurons after transient middle cerebral artery occlusion/reperfusion (tMCAO/R) in male mice, as well as oxygen glucose deprivation/reperfusion (OGD/R) and treatment with ER stress inducer (tunicamycin and thapsigargin) in neuronal cells. Conditional neuronal knockdown of <i>Tigar</i> aggravated the injury following ischemia-reperfusion, whereas overexpression of <i>Tigar</i> attenuated cerebral ischemic injury and ameliorated intraneuronal ER stress. Additionally, TIGAR overexpression reduced the elevation of ATF4 target genes and attenuated ER stress-induced cell death. Notably, TIGAR colocalized and interacted with ATF4 in the nucleus, inhibiting its downstream proapoptotic gene transcription, consequently protecting against ischemic injury. In vitro and in vivo experiments revealed that ATF4 overexpression reversed the protective effects of TIGAR against cerebral ischemic injury. Intriguingly, our study identified the Q141/K145 residues of TIGAR, crucial for its nuclear translocation and interaction with ATF4, highlighting a novel aspect of TIGAR's function distinct from its known phosphatase activity or mitochondrial localization domains. These findings reveal a novel neuroprotective mechanism of TIGAR in regulating ER stress through ATF4-mediated signaling pathways. These insights may guide targeted therapeutic strategies to protect neuronal function and alleviate the deleterious effects of cerebral ischemic injury.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371427","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}
引用次数: 0
Common and Unique Neurophysiological Processes That Support the Stopping and Revising of Actions.
IF 4.4 2区 医学
Journal of Neuroscience Pub Date : 2025-03-26 DOI: 10.1523/JNEUROSCI.1537-24.2025
Mario Hervault, Jan R Wessel
{"title":"Common and Unique Neurophysiological Processes That Support the Stopping and Revising of Actions.","authors":"Mario Hervault, Jan R Wessel","doi":"10.1523/JNEUROSCI.1537-24.2025","DOIUrl":"10.1523/JNEUROSCI.1537-24.2025","url":null,"abstract":"<p><p>Inhibitory control is a crucial cognitive-control ability for behavioral flexibility, which has been extensively investigated through action-stopping tasks. Multiple neurophysiological features have been proposed as \"signatures\" of inhibitory control during action-stopping, though the processes indexed by these signatures are still controversially discussed. The present study aimed to disentangle these processes by comparing simple stopping situations with those in which additional action revisions were needed. Three experiments in female and male humans were performed to characterize the neurophysiological dynamics involved in action-stopping and action-changing, with hypotheses derived from recently developed two-stage \"pause-then-cancel\" models of inhibitory control. Both stopping and revising an action triggered an early, broad \"pause\"-process, marked by frontal EEG β-frequency bursting and nonselective suppression of corticospinal excitability. However, EMG showed that motor activity was only partially inhibited by this \"pause\" and that this activity could be modulated during action revision. In line with two-stage models of inhibitory control, subsequent frontocentral EEG activity after this initial \"pause\" selectively scaled depending on the required action revisions, with more activity observed for more complex revisions. This demonstrates the presence of a selective, effector-specific \"retune\" phase as the second process involved in action-stopping and action revision. Together, these findings show that inhibitory control is implemented over an extended period of time and in at least two phases. We are further able to align the most commonly proposed neurophysiological signatures to these phases and show that they are differentially modulated by the complexity of action revision.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257320","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}
引用次数: 0
Identification of a Novel Population of Neuromedin S Expressing Neurons in the Ventral Tegmental Area That Promote Morphine-Elicited Behavior.
IF 4.4 2区 医学
Journal of Neuroscience Pub Date : 2025-03-26 DOI: 10.1523/JNEUROSCI.1662-24.2025
Cristina Rivera Quiles, Sarah C Simmons, Olivia Dodson, Milagros Alday, Nicole Camacho Fontánez, Samantha Caico, Amber Garrison, Fatemeh Shafieichaharberoud, Xuefei Huang, Qiwen Hu, Elizabeth A Heller, Michelle S Mazei-Robison
{"title":"Identification of a Novel Population of Neuromedin S Expressing Neurons in the Ventral Tegmental Area That Promote Morphine-Elicited Behavior.","authors":"Cristina Rivera Quiles, Sarah C Simmons, Olivia Dodson, Milagros Alday, Nicole Camacho Fontánez, Samantha Caico, Amber Garrison, Fatemeh Shafieichaharberoud, Xuefei Huang, Qiwen Hu, Elizabeth A Heller, Michelle S Mazei-Robison","doi":"10.1523/JNEUROSCI.1662-24.2025","DOIUrl":"10.1523/JNEUROSCI.1662-24.2025","url":null,"abstract":"<p><p>Opioid use disorder constitutes a major health and economic burden, but our limited understanding of the underlying neurobiology impedes better interventions. Alteration in the activity and output of dopamine (DA) neurons in the ventral tegmental area (VTA) contributes to drug effects, but the mechanisms underlying these changes remain relatively unexplored. We used translating ribosome affinity purification (TRAP) and RNA sequencing to identify gene expression changes in mouse VTA DA neurons following chronic morphine exposure. We found that expression of the neuropeptide neuromedin S (NMS) is robustly increased in VTA DA neurons by morphine. Using an NMS-iCre driver line, we confirmed that a subset of VTA neurons express NMS and that chemogenetic modulation of VTA NMS neuron activity altered morphine responses in male and female mice. Specifically, VTA NMS neuronal activation promoted morphine locomotor activity while inhibition reduced morphine locomotor activity and conditioned place preference. Interestingly, these effects appear specific to morphine, as modulation of VTA NMS activity did not affect cocaine behaviors, consistent with our data that cocaine administration does not increase VTA <i>Nms</i> expression. Chemogenetic manipulation of VTA neurons that express glucagon-like peptide, a transcript also robustly increased in VTA DA neurons by morphine, does not alter morphine-elicited behavior, further highlighting the functional relevance of VTA NMS-expressing neurons. Together, our current data suggest that NMS-expressing neurons represent a novel subset of VTA neurons that may be functionally relevant for morphine responses and support the utility of cell-type-specific analyses like TRAP to identify neuronal adaptations underlying substance use disorder.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392364","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}
引用次数: 0
The cerebellum contributes to prediction error coding in reinforcement learning in humans.
IF 4.4 2区 医学
Journal of Neuroscience Pub Date : 2025-03-26 DOI: 10.1523/JNEUROSCI.1972-24.2025
Dana M Huvermann, Adam M Berlijn, Andreas Thieme, Friedrich Erdlenbruch, Stefan J Groiss, Andreas Deistung, Manfred Mittelstaedt, Elke Wondzinski, Heike Sievers, Benedikt Frank, Sophia L Göricke, Michael Gliem, Martin Köhrmann, Mario Siebler, Alfons Schnitzler, Christian Bellebaum, Martina Minnerop, Dagmar Timmann, Jutta Peterburs
{"title":"The cerebellum contributes to prediction error coding in reinforcement learning in humans.","authors":"Dana M Huvermann, Adam M Berlijn, Andreas Thieme, Friedrich Erdlenbruch, Stefan J Groiss, Andreas Deistung, Manfred Mittelstaedt, Elke Wondzinski, Heike Sievers, Benedikt Frank, Sophia L Göricke, Michael Gliem, Martin Köhrmann, Mario Siebler, Alfons Schnitzler, Christian Bellebaum, Martina Minnerop, Dagmar Timmann, Jutta Peterburs","doi":"10.1523/JNEUROSCI.1972-24.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.1972-24.2025","url":null,"abstract":"<p><p>Recent rodent data suggest that the cerebellum - a region typically associated with processing sensory prediction errors (PEs) - also processes PEs in reinforcement learning (RL-PEs; i.e., learning from action outcomes). We tested whether cerebellar output is necessary for RL-PE processing in regions more traditionally associated with action-outcome processing, such as striatum and anterior cingulate cortex. The feedback-related negativity (FRN) was measured as a proxy of cerebral RL-PE processing in a probabilistic feedback learning task using electroencephalography. Two complementary experiments were performed in humans. First, patients with chronic cerebellar stroke (20 male, 6 female) and matched healthy controls (19 male, 7 female) were tested. Second, single-pulse cerebellar transcranial magnetic stimulation (TMS) was applied in healthy participants (7 male, 17 female), thus implementing a virtual lesion approach. Consistent with previous studies, learning of action-outcome associations was intact with only minor changes in behavioural flexibility. Importantly, no significant RL-PE processing was observed in the FRN in patients with cerebellar stroke, and in participants receiving cerebellar TMS. Findings in both experiments show that RL-PE processing in the forebrain depends on cerebellar output in humans, complementing and extending previous findings in rodents.<b>Significance statement</b> While processing of prediction errors in reinforcement learning (RL-PEs) is usually attributed to midbrain and forebrain, recent rodent studies have recorded RL-PE signals in the cerebellum. It is not yet clear whether these cerebellar RL-PE signals contribute to RL-PE processing in the forebrain/midbrain. In the current study, we could show that forebrain RL-PE coding is blunted when the cerebellum is affected across two complementary lesion models (patients with cerebellar stroke, cerebellar TMS). Our results support direct involvement of the cerebellum in RL-PE processing. We can further show that the cerebellum is necessary for RL-PE coding in the forebrain.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732789","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}
引用次数: 0
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信