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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
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
Parkinsonism Disrupts Neuronal Modulation in the Presupplementary Motor Area during Movement Preparation.
IF 4.4 2区 医学
Journal of Neuroscience Pub Date : 2025-03-26 DOI: 10.1523/JNEUROSCI.1802-24.2025
Claudia M Hendrix, Hannah E Baker, Ying Yu, David D Schneck, Jing Wang, Luke A Johnson, Jerrold L Vitek
{"title":"Parkinsonism Disrupts Neuronal Modulation in the Presupplementary Motor Area during Movement Preparation.","authors":"Claudia M Hendrix, Hannah E Baker, Ying Yu, David D Schneck, Jing Wang, Luke A Johnson, Jerrold L Vitek","doi":"10.1523/JNEUROSCI.1802-24.2025","DOIUrl":"10.1523/JNEUROSCI.1802-24.2025","url":null,"abstract":"<p><p>Multiple studies suggest that Parkinson's disease (PD) is associated with changes in neuronal activity throughout the basal ganglia-thalamocortical motor circuit. There are limited electrophysiological data, however, describing how parkinsonism impacts neuronal activity in the presupplementary motor area (pre-SMA), an area in the medial frontal cortex involved in movement planning and motor control. In this study, single unit activity was recorded in the pre-SMA of two female nonhuman primates during a visually cued reaching task in both the naive and parkinsonian state using the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of parkinsonism. In the naive state, neuronal discharge rates were dynamically modulated prior to the presentation of the instructional go-cue. In a subset of these modulated cells, the magnitude of modulation correlated linearly with reaction time (RT). In the parkinsonian state, however, modulation of discharge rates in the pre-SMA was disrupted, and the predictive encoding of RT was significantly diminished. These findings add to our understanding of the role of pre-SMA in motor behavior and suggest that disrupted encoding in this cortical region contributes to the alteration of early preparatory and premovement processes present in Parkinson's disease.</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/PMC11949476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076206","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
Neural Processing of Taste-Related Signals in the Mediodorsal Thalamus of Mice.
IF 4.4 2区 医学
Journal of Neuroscience Pub Date : 2025-03-26 DOI: 10.1523/JNEUROSCI.1500-24.2025
Katherine E Odegaard, Cecilia G Bouaichi, Greg Owanga, Roberto Vincis
{"title":"Neural Processing of Taste-Related Signals in the Mediodorsal Thalamus of Mice.","authors":"Katherine E Odegaard, Cecilia G Bouaichi, Greg Owanga, Roberto Vincis","doi":"10.1523/JNEUROSCI.1500-24.2025","DOIUrl":"10.1523/JNEUROSCI.1500-24.2025","url":null,"abstract":"<p><p>Our consummatory decisions depend on the taste of food and the reward experienced while eating, which are processed through neural computations in interconnected brain areas. Although many gustatory regions of rodents have been explored, the mediodorsal nucleus of the thalamus (MD) remains understudied. The MD, a multimodal brain area connected with gustatory centers, is often studied for its role in processing associative and cognitive information and has been shown to represent intraorally delivered chemosensory stimuli after strong retronasal odor-taste associations. Key questions remain about whether MD neurons can process taste quality independently of odor-taste associations and how they represent extraoral signals predicting rewarding and aversive gustatory outcomes. Here, using C57 male and female mice we present electrophysiological evidence demonstrating how MD neurons represent and encode 1) the identity and concentrations of basic taste qualities during active licking, and 2) auditory signals anticipating rewarding and aversive taste outcomes. Our data reveal that MD neurons can reliably and dynamically encode taste identity in a broadly tuned manner and taste concentrations with spiking activity positively and negatively correlated with stimulus intensity. Our data also show that MD can represent information related to predictive cues and their associated outcomes, regardless of whether the cue predicts a rewarding or aversive outcome. In summary, our findings suggest that the mediodorsal thalamus is integral to the taste pathway, as it can encode sensory-discriminative dimensions of tastants and participate in processing associative information essential for ingestive behaviors.<b>Significance Statement</b> Dietary decisions are driven by the taste of the food and the reward experienced while eating. This information is processed through neural computations across interconnected brain areas. Given its neural connections, the mediodorsal thalamus (MD) could be part of this network. However, its involvement in gustatory processing is largely ignored. This study examines how MD neurons respond to taste quality, intensity, and expectation by analyzing the electrical activity of MD neurons in mice allowed to freely lick a spout to obtain different tastes. Our findings support the idea that the MD is part of the brain network responsible for processing sensory and associative information relevant to eating.</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":"143732786","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
The Astrocytic Zinc Transporter ZIP12 Is a Synaptic Protein That Contributes to Synaptic Zinc Levels in the Mouse Auditory Cortex. 星形细胞锌转运蛋白ZIP12是一种突触蛋白,与小鼠听觉皮层突触锌水平有关。
IF 4.4 2区 医学
Journal of Neuroscience Pub Date : 2025-03-26 DOI: 10.1523/JNEUROSCI.2067-24.2025
Abbey Manning, Benjamin Z Mendelson, Philip T R Bender, Kaitlin Bainer, Rayli Ruby, Victoria R Shifflett, Donald F Dariano, Bradley A Webb, Werner J Geldenhuys, Charles T Anderson
{"title":"The Astrocytic Zinc Transporter ZIP12 Is a Synaptic Protein That Contributes to Synaptic Zinc Levels in the Mouse Auditory Cortex.","authors":"Abbey Manning, Benjamin Z Mendelson, Philip T R Bender, Kaitlin Bainer, Rayli Ruby, Victoria R Shifflett, Donald F Dariano, Bradley A Webb, Werner J Geldenhuys, Charles T Anderson","doi":"10.1523/JNEUROSCI.2067-24.2025","DOIUrl":"10.1523/JNEUROSCI.2067-24.2025","url":null,"abstract":"<p><p>Synaptically released zinc is a neuronal signaling system that arises from the actions of the presynaptic vesicular zinc transporter protein zinc transporter 3 (ZnT3). Mechanisms that regulate the actions of zinc at synapses are of great importance for many aspects of synaptic signaling in the brain. Here, we identify the astrocytic zinc transporter protein ZIP12 as a candidate mechanism that contributes to zinc clearance at cortical synapses. We identify small-molecule compounds that antagonize the function of ZIP12 in heterologous expression systems, and we use one of these compounds, ZIP12 modulator 8, to increase the concentration of ZnT3-dependent zinc at synapses in the brain of male and female mice to inhibit the activity of neuronal AMPA and NMDA glutamate receptors. These results identify a cellular mechanism and provide a pharmacological toolbox to target the molecular machinery that supports the actions of synaptic zinc in the brain.</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/PMC11949477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985339","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 Role of Claustrum in Incubation of Opioid Seeking after Electric Barrier-Induced Voluntary Abstinence in Male and Female Rats.
IF 4.4 2区 医学
Journal of Neuroscience Pub Date : 2025-03-26 DOI: 10.1523/JNEUROSCI.0561-24.2025
Kenichiro Negishi, Ying Duan, Ashley Batista, Mona S Pishgar, Pei-Jung Tsai, Kiera E Caldwell, Sarah M Claypool, David J Reiner, Rajtarun Madangopal, Jennifer M Bossert, Yihong Yang, Yavin Shaham, Ida Fredriksson
{"title":"The Role of Claustrum in Incubation of Opioid Seeking after Electric Barrier-Induced Voluntary Abstinence in Male and Female Rats.","authors":"Kenichiro Negishi, Ying Duan, Ashley Batista, Mona S Pishgar, Pei-Jung Tsai, Kiera E Caldwell, Sarah M Claypool, David J Reiner, Rajtarun Madangopal, Jennifer M Bossert, Yihong Yang, Yavin Shaham, Ida Fredriksson","doi":"10.1523/JNEUROSCI.0561-24.2025","DOIUrl":"10.1523/JNEUROSCI.0561-24.2025","url":null,"abstract":"<p><p>We previously reported that ventral subiculum (vSub) activity is critical to incubation of oxycodone seeking after abstinence induced by adverse consequences of drug seeking. Here, we studied the role of claustrum, a key vSub input, in this incubation. We trained male and female rats to self-administer oxycodone for 2 weeks and then induced abstinence by exposing them to an electric barrier for 2 weeks. We used retrograde tracing (cholera toxin B subunit) plus the activity marker Fos to identify projections to vSub cactivated during \"incubated\" relapse (Abstinence Day 15). We then used pharmacological reversible inactivation to determine the causal role of claustrum in incubation and the behavioral and anatomical specificity of this role. We also used an anatomical disconnection procedure to determine the causal role of claustrum-vSub connections in incubation. Finally, we analyzed an existing functional MRI dataset to determine if functional connectivity changes in claustrum-related circuits predict incubation of oxycodone seeking. Claustrum neurons projecting to vSub were activated during relapse tests after electric barrier-induced abstinence. Inactivation of claustrum but not areas dorsolateral to claustrum decreased incubation of oxycodone seeking after electric barrier-induced abstinence; claustrum inactivation had no effect on incubation after food choice-induced abstinence. Both ipsilateral and contralateral inactivation of claustrum-vSub projections decreased incubation after electric barrier-induced abstinence. Functional connectivity changes in claustrum-cortical circuits during electric barrier-induced abstinence predicted incubated oxycodone relapse. Our study identified a novel role of claustrum in relapse to opioid drugs after abstinence induced by adverse consequences of drug seeking.</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/PMC11949475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400526","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
DISRUPTION OF TRANSTHALAMIC CIRCUITRY FROM PRIMARY VISUAL CORTEX IMPAIRS VISUAL DISCRIMINATION IN MICE.
IF 4.4 2区 医学
Journal of Neuroscience Pub Date : 2025-03-26 DOI: 10.1523/JNEUROSCI.0002-25.2025
C McKinnon, C Mo, S M Sherman
{"title":"DISRUPTION OF TRANSTHALAMIC CIRCUITRY FROM PRIMARY VISUAL CORTEX IMPAIRS VISUAL DISCRIMINATION IN MICE.","authors":"C McKinnon, C Mo, S M Sherman","doi":"10.1523/JNEUROSCI.0002-25.2025","DOIUrl":"10.1523/JNEUROSCI.0002-25.2025","url":null,"abstract":"<p><p>Layer 5 (L5) of the cortex provides strong driving input to higher-order thalamic nuclei, such as the pulvinar in the visual system, forming the basis of cortico-thalamo-cortical (transthalamic) circuits. These circuits provide a communication route between cortical areas in parallel to direct corticocortical connections, but their specific role in perception and behavior remains unclear. Using targeted optogenetic inhibition in mice of both sexes performing a visual discrimination task, we selectively suppressed the corticothalamic input from L5 cells in primary visual cortex (V1) at their terminals in pulvinar. This suppresses transthalamic circuits from V1; furthermore, any effect on direct corticocortical projections and local V1 circuitry would thus result from transthalamic inputs (e.g., V1 to pulvinar back to V1 (Miller-Hansen and Sherman, 2022). Such suppression of transthalamic processing during visual stimulus presentation of drifting gratings significantly impaired discrimination performance across different orientations. The impact on behavior was specific to the portion of visual space that retinotopically coincided with the V1 L5 corticothalamic inhibition. These results highlight the importance of incorporating L5-initiated transthalamic circuits into cortical processing frameworks, particularly those addressing how the hierarchical propagation of sensory signals supports perceptual decision-making.<b>Significance statement</b> Appreciation of pathways for transthalamic communication between cortical areas, organized in parallel with direct connections, has transformed our thinking about cortical functioning writ large. Studies of transthalamic pathways initially concentrated on their anatomy and physiology, but there has been a shift towards understanding their importance to cognitive behavior. Here, we have used an optogenetic approach in mice to selectively inhibit the transthalamic pathway from primary visual cortex to other cortical areas and back to itself. We find that such inhibition degrades the animals' ability to discriminate, showing for the first time that specific inhibition of visual transthalamic circuitry reduces visual discrimination. This causal data adds to the growing evidence for the importance of transthalamic signaling in perceptual processing.</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":"143732854","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
The Electrically Silent Kv5.1 Subunit Forms Heteromeric Kv2 Channels in Cortical Neurons and Confers Distinct Functional Properties.
IF 4.4 2区 医学
Journal of Neuroscience Pub Date : 2025-03-26 DOI: 10.1523/JNEUROSCI.2293-23.2025
Michael Ferns, Deborah van der List, Nicholas C Vierra, Taylor Lacey, Karl Murray, Michael Kirmiz, Robert G Stewart, Jon T Sack, James S Trimmer
{"title":"The Electrically Silent Kv5.1 Subunit Forms Heteromeric Kv2 Channels in Cortical Neurons and Confers Distinct Functional Properties.","authors":"Michael Ferns, Deborah van der List, Nicholas C Vierra, Taylor Lacey, Karl Murray, Michael Kirmiz, Robert G Stewart, Jon T Sack, James S Trimmer","doi":"10.1523/JNEUROSCI.2293-23.2025","DOIUrl":"10.1523/JNEUROSCI.2293-23.2025","url":null,"abstract":"<p><p>Voltage-gated K<sup>+</sup> channels of the Kv2 family are highly expressed in brain and play dual roles in regulating neuronal excitability and in organizing endoplasmic reticulum-plasma membrane (ER-PM) junctions. Studies in heterologous cells suggest that Kv2.1 and Kv2.2 co-assemble with \"electrically silent\" KvS subunits to form heterotetrameric channels with distinct biophysical properties, but the prevalence and localization of these channels in native neurons are unknown. Here, using mass spectrometry-based proteomics, we identified five KvS subunits as components of native Kv2.1 channels immunopurified from mouse brain of both sexes, the most abundant being Kv5.1. We found that Kv5.1 co-immunoprecipitates with Kv2.1 and to a lesser extent with Kv2.2 from brain lysates and that Kv5.1 protein levels are decreased by 70% in Kv2.1 knock-out mice and 95% in Kv2.1/Kv2.2 double knock-out mice. RNAscope and immunolabeling revealed that Kv5.1 is prominently expressed in neocortex, where it is detected in a substantial fraction of Kv2.1/Kv2.2 positive neurons in layers 2/3, 5, and 6. At the subcellular level, Kv5.1 protein is coclustered with Kv2.1 and Kv2.2 at presumptive ER-PM junctions on the soma and proximal dendrites of cortical neurons. Moreover, in addition to modifying channel conductance, we found that Kv2/Kv5.1 channels are less phosphorylated and insensitive to RY785, a potent and selective Kv2 channel inhibitor. Together, these findings demonstrate that KvS subunits create multiple Kv2 channel subtypes in brain. Most notably, Kv2/Kv5.1 channels are highly expressed in cortical neurons, where their unique properties likely modulate the critical conducting and nonconducting roles of Kv2 channels.</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/PMC11949482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400538","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
Distinct Patterns of PV and SST GABAergic Neuronal Activity in the Basal Forebrain during Olfactory-Guided Behavior in Mice.
IF 4.4 2区 医学
Journal of Neuroscience Pub Date : 2025-03-26 DOI: 10.1523/JNEUROSCI.0200-24.2025
Elizabeth H Moss, Evelyne K Tantry, Elaine Le, Pey-Shyuan Chin, Priscilla Ambrosi, Katie L Brandel-Ankrapp, Benjamin R Arenkiel
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