Pub Date : 2024-11-02DOI: 10.1016/j.neuron.2024.10.010
Guillermo Aquino-Miranda, Dounya Jalloul, Xu O Zhang, Sa Li, Gilbert J Kirouac, Michael Beierlein, Fabricio H Do Monte
Corticothalamic projections to sensorimotor thalamic nuclei show modest firing rates and serve to modulate the activity of thalamic relay neurons. By contrast, here we find that high-order corticothalamic projections from the prelimbic (PL) cortex to the anterior paraventricular thalamic nucleus (aPVT) maintain high-frequency activity and evoke strong synaptic excitation of aPVT neurons in rats. In a significant fraction of aPVT cells, such high-frequency excitation of PL-aPVT projections leads to a rapid decay of action potential amplitudes, followed by a depolarization block (DB) that strongly limits aPVT maximum firing rates, thereby regulating both defensive and appetitive behaviors in a frequency-dependent manner. Strong inhibitory inputs from the anteroventral portion of the thalamic reticular nucleus (avTRN) inhibit the firing rate of aPVT neurons during periods of high-spike fidelity but restore it during prominent DB, suggesting that avTRN activity can modulate the effects of PL inputs on aPVT firing rates to ultimately control motivated behaviors.
{"title":"Functional properties of corticothalamic circuits targeting paraventricular thalamic neurons.","authors":"Guillermo Aquino-Miranda, Dounya Jalloul, Xu O Zhang, Sa Li, Gilbert J Kirouac, Michael Beierlein, Fabricio H Do Monte","doi":"10.1016/j.neuron.2024.10.010","DOIUrl":"https://doi.org/10.1016/j.neuron.2024.10.010","url":null,"abstract":"<p><p>Corticothalamic projections to sensorimotor thalamic nuclei show modest firing rates and serve to modulate the activity of thalamic relay neurons. By contrast, here we find that high-order corticothalamic projections from the prelimbic (PL) cortex to the anterior paraventricular thalamic nucleus (aPVT) maintain high-frequency activity and evoke strong synaptic excitation of aPVT neurons in rats. In a significant fraction of aPVT cells, such high-frequency excitation of PL-aPVT projections leads to a rapid decay of action potential amplitudes, followed by a depolarization block (DB) that strongly limits aPVT maximum firing rates, thereby regulating both defensive and appetitive behaviors in a frequency-dependent manner. Strong inhibitory inputs from the anteroventral portion of the thalamic reticular nucleus (avTRN) inhibit the firing rate of aPVT neurons during periods of high-spike fidelity but restore it during prominent DB, suggesting that avTRN activity can modulate the effects of PL inputs on aPVT firing rates to ultimately control motivated behaviors.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-31DOI: 10.1016/j.neuron.2024.10.009
Jonathan W Lovelace, Jingrui Ma, Vineet Augustine
Interoception, the sensation and perception of internal bodily states, should be conceptualized through specialized modalities like cardioception, pulmoception, gastroception, and uroception. This NeuroView emphasizes cardioception, exploring heart-brain interactions, cardiac reflexes, and their influence on mental states and behavior.
{"title":"Defining cardioception: Heart-brain crosstalk.","authors":"Jonathan W Lovelace, Jingrui Ma, Vineet Augustine","doi":"10.1016/j.neuron.2024.10.009","DOIUrl":"https://doi.org/10.1016/j.neuron.2024.10.009","url":null,"abstract":"<p><p>Interoception, the sensation and perception of internal bodily states, should be conceptualized through specialized modalities like cardioception, pulmoception, gastroception, and uroception. This NeuroView emphasizes cardioception, exploring heart-brain interactions, cardiac reflexes, and their influence on mental states and behavior.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-31DOI: 10.1016/j.neuron.2024.10.007
Norah Al-Azzam, Jenny H To, Vaishali Gautam, Lena A Street, Chloe B Nguyen, Jack T Naritomi, Dylan C Lam, Assael A Madrigal, Benjamin Lee, Wenhao Jin, Anthony Avina, Orel Mizrahi, Jasmine R Mueller, Willard Ford, Cara R Schiavon, Elena Rebollo, Anthony Q Vu, Steven M Blue, Yashwin L Madakamutil, Uri Manor, Jeffrey D Rothstein, Alyssa N Coyne, Marko Jovanovic, Gene W Yeo
Amyotrophic lateral sclerosis (ALS) is linked to the reduction of certain nucleoporins in neurons. Increased nuclear localization of charged multivesicular body protein 7 (CHMP7), a protein involved in nuclear pore surveillance, has been identified as a key factor damaging nuclear pores and disrupting transport. Using CRISPR-based microRaft, followed by gRNA identification (CRaft-ID), we discovered 55 RNA-binding proteins (RBPs) that influence CHMP7 localization, including SmD1, a survival of motor neuron (SMN) complex component. Immunoprecipitation-mass spectrometry (IP-MS) and enhanced crosslinking and immunoprecipitation (CLIP) analyses revealed CHMP7's interactions with SmD1, small nuclear RNAs, and splicing factor mRNAs in motor neurons (MNs). ALS induced pluripotent stem cell (iPSC)-MNs show reduced SmD1 expression, and inhibiting SmD1/SMN complex increased CHMP7 nuclear localization. Crucially, overexpressing SmD1 in ALS iPSC-MNs restored CHMP7's cytoplasmic localization and corrected STMN2 splicing. Our findings suggest that early ALS pathogenesis is driven by SMN complex dysregulation.
{"title":"Inhibition of RNA splicing triggers CHMP7 nuclear entry, impacting TDP-43 function and leading to the onset of ALS cellular phenotypes.","authors":"Norah Al-Azzam, Jenny H To, Vaishali Gautam, Lena A Street, Chloe B Nguyen, Jack T Naritomi, Dylan C Lam, Assael A Madrigal, Benjamin Lee, Wenhao Jin, Anthony Avina, Orel Mizrahi, Jasmine R Mueller, Willard Ford, Cara R Schiavon, Elena Rebollo, Anthony Q Vu, Steven M Blue, Yashwin L Madakamutil, Uri Manor, Jeffrey D Rothstein, Alyssa N Coyne, Marko Jovanovic, Gene W Yeo","doi":"10.1016/j.neuron.2024.10.007","DOIUrl":"10.1016/j.neuron.2024.10.007","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is linked to the reduction of certain nucleoporins in neurons. Increased nuclear localization of charged multivesicular body protein 7 (CHMP7), a protein involved in nuclear pore surveillance, has been identified as a key factor damaging nuclear pores and disrupting transport. Using CRISPR-based microRaft, followed by gRNA identification (CRaft-ID), we discovered 55 RNA-binding proteins (RBPs) that influence CHMP7 localization, including SmD1, a survival of motor neuron (SMN) complex component. Immunoprecipitation-mass spectrometry (IP-MS) and enhanced crosslinking and immunoprecipitation (CLIP) analyses revealed CHMP7's interactions with SmD1, small nuclear RNAs, and splicing factor mRNAs in motor neurons (MNs). ALS induced pluripotent stem cell (iPSC)-MNs show reduced SmD1 expression, and inhibiting SmD1/SMN complex increased CHMP7 nuclear localization. Crucially, overexpressing SmD1 in ALS iPSC-MNs restored CHMP7's cytoplasmic localization and corrected STMN2 splicing. Our findings suggest that early ALS pathogenesis is driven by SMN complex dysregulation.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-29DOI: 10.1016/j.neuron.2024.10.008
Jessica A F Thompson, Hannah Sheahan, Tsvetomira Dumbalska, Julian D Sandbrink, Manuela Piazza, Christopher Summerfield
To understand a visual scene, observers need to both recognize objects and encode relational structure. For example, a scene comprising three apples requires the observer to encode concepts of "apple" and "three." In the primate brain, these functions rely on dual (ventral and dorsal) processing streams. Object recognition in primates has been successfully modeled with deep neural networks, but how scene structure (including numerosity) is encoded remains poorly understood. Here, we built a deep learning model, based on the dual-stream architecture of the primate brain, which is able to count items "zero-shot"-even if the objects themselves are unfamiliar. Our dual-stream network forms spatial response fields and lognormal number codes that resemble those observed in the macaque posterior parietal cortex. The dual-stream network also makes successful predictions about human counting behavior. Our results provide evidence for an enactive theory of the role of the posterior parietal cortex in visual scene understanding.
{"title":"Zero-shot counting with a dual-stream neural network model.","authors":"Jessica A F Thompson, Hannah Sheahan, Tsvetomira Dumbalska, Julian D Sandbrink, Manuela Piazza, Christopher Summerfield","doi":"10.1016/j.neuron.2024.10.008","DOIUrl":"https://doi.org/10.1016/j.neuron.2024.10.008","url":null,"abstract":"<p><p>To understand a visual scene, observers need to both recognize objects and encode relational structure. For example, a scene comprising three apples requires the observer to encode concepts of \"apple\" and \"three.\" In the primate brain, these functions rely on dual (ventral and dorsal) processing streams. Object recognition in primates has been successfully modeled with deep neural networks, but how scene structure (including numerosity) is encoded remains poorly understood. Here, we built a deep learning model, based on the dual-stream architecture of the primate brain, which is able to count items \"zero-shot\"-even if the objects themselves are unfamiliar. Our dual-stream network forms spatial response fields and lognormal number codes that resemble those observed in the macaque posterior parietal cortex. The dual-stream network also makes successful predictions about human counting behavior. Our results provide evidence for an enactive theory of the role of the posterior parietal cortex in visual scene understanding.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-25DOI: 10.1016/j.neuron.2024.10.005
Reza Rajimehr, Haoran Xu, Asa Farahani, Simon Kornblith, John Duncan, Robert Desimone
Characterizing the functional organization of cerebral cortex is a fundamental step in understanding how different kinds of information are processed in the brain. However, it is still unclear how these areas are organized during naturalistic visual and auditory stimulation. Here, we used high-resolution functional MRI data from 176 human subjects to map the macro-architecture of the entire cerebral cortex based on responses to a 60-min audiovisual movie stimulus. A data-driven clustering approach revealed a map of 24 functional areas/networks, each explicitly linked to a specific aspect of sensory or cognitive processing. Novel features of this map included an extended scene-selective network in the lateral prefrontal cortex, separate clusters responsive to human-object and human-human interaction, and a push-pull interaction between three executive control (domain-general) networks and domain-specific regions of the visual, auditory, and language cortex. Our cortical parcellation provides a comprehensive and unified map of functionally defined areas in the human cerebral cortex.
{"title":"Functional architecture of cerebral cortex during naturalistic movie watching.","authors":"Reza Rajimehr, Haoran Xu, Asa Farahani, Simon Kornblith, John Duncan, Robert Desimone","doi":"10.1016/j.neuron.2024.10.005","DOIUrl":"https://doi.org/10.1016/j.neuron.2024.10.005","url":null,"abstract":"<p><p>Characterizing the functional organization of cerebral cortex is a fundamental step in understanding how different kinds of information are processed in the brain. However, it is still unclear how these areas are organized during naturalistic visual and auditory stimulation. Here, we used high-resolution functional MRI data from 176 human subjects to map the macro-architecture of the entire cerebral cortex based on responses to a 60-min audiovisual movie stimulus. A data-driven clustering approach revealed a map of 24 functional areas/networks, each explicitly linked to a specific aspect of sensory or cognitive processing. Novel features of this map included an extended scene-selective network in the lateral prefrontal cortex, separate clusters responsive to human-object and human-human interaction, and a push-pull interaction between three executive control (domain-general) networks and domain-specific regions of the visual, auditory, and language cortex. Our cortical parcellation provides a comprehensive and unified map of functionally defined areas in the human cerebral cortex.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-24DOI: 10.1016/j.neuron.2024.10.004
Ugurcan Mugan, Samantha L Hoffman, A David Redish
Behavior in naturalistic scenarios occurs in diverse environments. Adaptive strategies rely on multiple neural circuits and competing decision systems. However, past studies of rodent decision making have largely measured behavior in simple environments. To fill this gap, we recorded neural ensembles from hippocampus (HC), dorsolateral striatum (DLS), and dorsomedial prefrontal cortex (dmPFC) while rats foraged for food under changing rules in environments with varying topological complexity. Environmental complexity increased behavioral variability, lengthened HC nonlocal sequences, and modulated action caching. We found contrasting representations between DLS and HC, supporting a competition between decision systems. dmPFC activity was indicative of setting this balance, in particular predicting the extent of HC non-local coding. Inactivating mPFC impaired short-term behavioral adaptation and produced long-term deficits in balancing decision systems. Our findings reveal the dynamic nature of decision-making systems and how environmental complexity modulates their engagement with implications for behavior in naturalistic environments.
自然场景中的行为发生在不同的环境中。适应策略依赖于多个神经回路和相互竞争的决策系统。然而,过去对啮齿动物决策制定的研究大多是在简单环境中测量行为。为了填补这一空白,我们记录了海马(HC)、背外侧纹状体(DLS)和背内侧前额叶皮层(dmPFC)的神经集合,当时大鼠正在拓扑复杂程度不同的环境中根据不断变化的规则觅食。环境的复杂性增加了行为的可变性,延长了HC非局部序列,并调节了动作缓存。我们发现 DLS 和 HC 之间的表征形成了鲜明对比,这支持了决策系统之间的竞争。dmPFC 的活动表明了这种平衡的设定,尤其是预测 HC 非本地编码的程度。使 mPFC 失活会损害短期行为适应,并产生平衡决策系统的长期缺陷。我们的研究结果揭示了决策系统的动态性质,以及环境复杂性如何调节决策系统的参与,并对自然环境中的行为产生影响。
{"title":"Environmental complexity modulates information processing and the balance between decision-making systems.","authors":"Ugurcan Mugan, Samantha L Hoffman, A David Redish","doi":"10.1016/j.neuron.2024.10.004","DOIUrl":"https://doi.org/10.1016/j.neuron.2024.10.004","url":null,"abstract":"<p><p>Behavior in naturalistic scenarios occurs in diverse environments. Adaptive strategies rely on multiple neural circuits and competing decision systems. However, past studies of rodent decision making have largely measured behavior in simple environments. To fill this gap, we recorded neural ensembles from hippocampus (HC), dorsolateral striatum (DLS), and dorsomedial prefrontal cortex (dmPFC) while rats foraged for food under changing rules in environments with varying topological complexity. Environmental complexity increased behavioral variability, lengthened HC nonlocal sequences, and modulated action caching. We found contrasting representations between DLS and HC, supporting a competition between decision systems. dmPFC activity was indicative of setting this balance, in particular predicting the extent of HC non-local coding. Inactivating mPFC impaired short-term behavioral adaptation and produced long-term deficits in balancing decision systems. Our findings reveal the dynamic nature of decision-making systems and how environmental complexity modulates their engagement with implications for behavior in naturalistic environments.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-23DOI: 10.1016/j.neuron.2024.09.022
Mojtaba Abbaszadeh, Becket Ebitz
People often underperform their abilities in high-value situations, a mysterious phenomenon known as "choking under pressure." In this issue of Neuron, Smoulder et al.1 report that target-selective signals in the motor cortex of non-human primates collapse in the face of high-value opportunities.
{"title":"When rewards backfire: Collapsing under pressure in motor cortex.","authors":"Mojtaba Abbaszadeh, Becket Ebitz","doi":"10.1016/j.neuron.2024.09.022","DOIUrl":"https://doi.org/10.1016/j.neuron.2024.09.022","url":null,"abstract":"<p><p>People often underperform their abilities in high-value situations, a mysterious phenomenon known as \"choking under pressure.\" In this issue of Neuron, Smoulder et al.<sup>1</sup> report that target-selective signals in the motor cortex of non-human primates collapse in the face of high-value opportunities.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":"112 20","pages":"3373-3375"},"PeriodicalIF":14.7,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-23Epub Date: 2024-08-20DOI: 10.1016/j.neuron.2024.07.022
Mark A Nicholas, Eric A Yttri
Striatum and its predominant input, motor cortex, are responsible for the selection and performance of purposive movement, but how their interaction guides these processes is not understood. To establish its neural and behavioral contributions, we bilaterally lesioned motor cortex and recorded striatal activity and reaching performance daily, capturing the lesion's direct ramifications within hours of the intervention. We observed reaching impairment and an absence of striatal motoric activity following lesion of motor cortex, but not parietal cortex control lesions. Although some aspects of performance began to recover after 8-10 days, striatal projection and interneuronal dynamics did not-eventually entering a non-motor encoding state that aligned with persisting kinematic control deficits. Lesioned mice also exhibited a profound inability to switch motor plans while locomoting, reminiscent of clinical freezing of gait (FOG). Our results demonstrate the necessity of motor cortex in generating trained and untrained actions as well as striatal motoric dynamics.
{"title":"Motor cortex is responsible for motoric dynamics in striatum and the execution of both skilled and unskilled actions.","authors":"Mark A Nicholas, Eric A Yttri","doi":"10.1016/j.neuron.2024.07.022","DOIUrl":"10.1016/j.neuron.2024.07.022","url":null,"abstract":"<p><p>Striatum and its predominant input, motor cortex, are responsible for the selection and performance of purposive movement, but how their interaction guides these processes is not understood. To establish its neural and behavioral contributions, we bilaterally lesioned motor cortex and recorded striatal activity and reaching performance daily, capturing the lesion's direct ramifications within hours of the intervention. We observed reaching impairment and an absence of striatal motoric activity following lesion of motor cortex, but not parietal cortex control lesions. Although some aspects of performance began to recover after 8-10 days, striatal projection and interneuronal dynamics did not-eventually entering a non-motor encoding state that aligned with persisting kinematic control deficits. Lesioned mice also exhibited a profound inability to switch motor plans while locomoting, reminiscent of clinical freezing of gait (FOG). Our results demonstrate the necessity of motor cortex in generating trained and untrained actions as well as striatal motoric dynamics.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"3486-3501.e5"},"PeriodicalIF":14.7,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-23Epub Date: 2024-06-25DOI: 10.1016/j.neuron.2024.05.029
Nikola Grujic, Rafael Polania, Denis Burdakov
Pupil size is a widely used metric of brain state. It is one of the few signals originating from the brain that can be readily monitored with low-cost devices in basic science, clinical, and home settings. It is, therefore, important to investigate and generate well-defined theories related to specific interpretations of this metric. What exactly does it tell us about the brain? Pupils constrict in response to light and dilate during darkness, but the brain also controls pupil size irrespective of luminosity. Pupil size fluctuations resulting from ongoing "brain states" are used as a metric of arousal, but what is pupil-linked arousal and how should it be interpreted in neural, cognitive, and computational terms? Here, we discuss some recent findings related to these issues. We identify open questions and propose how to answer them through a combination of well-defined tasks, neurocomputational models, and neurophysiological probing of the interconnected loops of causes and consequences of pupil size.
{"title":"Neurobehavioral meaning of pupil size.","authors":"Nikola Grujic, Rafael Polania, Denis Burdakov","doi":"10.1016/j.neuron.2024.05.029","DOIUrl":"10.1016/j.neuron.2024.05.029","url":null,"abstract":"<p><p>Pupil size is a widely used metric of brain state. It is one of the few signals originating from the brain that can be readily monitored with low-cost devices in basic science, clinical, and home settings. It is, therefore, important to investigate and generate well-defined theories related to specific interpretations of this metric. What exactly does it tell us about the brain? Pupils constrict in response to light and dilate during darkness, but the brain also controls pupil size irrespective of luminosity. Pupil size fluctuations resulting from ongoing \"brain states\" are used as a metric of arousal, but what is pupil-linked arousal and how should it be interpreted in neural, cognitive, and computational terms? Here, we discuss some recent findings related to these issues. We identify open questions and propose how to answer them through a combination of well-defined tasks, neurocomputational models, and neurophysiological probing of the interconnected loops of causes and consequences of pupil size.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"3381-3395"},"PeriodicalIF":14.7,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141458348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-23Epub Date: 2024-08-16DOI: 10.1016/j.neuron.2024.07.018
Guilian Tian, Katrina Bartas, May Hui, Lingxuan Chen, Jose J Vasquez, Ghalia Azouz, Pieter Derdeyn, Rían W Manville, Erick L Ho, Amanda S Fang, Yuan Li, Isabella Tyler, Vincent Setola, Jason Aoto, Geoffrey W Abbott, Kevin T Beier
The globus pallidus externus (GPe) is a central component of the basal ganglia circuit that acts as a gatekeeper of cocaine-induced behavioral plasticity. However, the molecular and circuit mechanisms underlying this function are unknown. Here, we show that GPe parvalbumin-positive (GPePV) cells mediate cocaine responses by selectively modulating ventral tegmental area dopamine (VTADA) cells projecting to the dorsomedial striatum (DMS). Interestingly, GPePV cell activity in cocaine-naive mice is correlated with behavioral responses following cocaine, effectively predicting cocaine sensitivity. Expression of the voltage-gated potassium channels KCNQ3 and KCNQ5 that control intrinsic cellular excitability following cocaine was downregulated, contributing to the elevation in GPePV cell excitability. Acutely activating channels containing KCNQ3 and/or KCNQ5 using the small molecule carnosic acid, a key psychoactive component of Salvia rosmarinus (rosemary) extract, reduced GPePV cell excitability and impaired cocaine reward, sensitization, and volitional cocaine intake, indicating its therapeutic potential to counteract psychostimulant use disorder.
{"title":"Molecular and circuit determinants in the globus pallidus mediating control of cocaine-induced behavioral plasticity.","authors":"Guilian Tian, Katrina Bartas, May Hui, Lingxuan Chen, Jose J Vasquez, Ghalia Azouz, Pieter Derdeyn, Rían W Manville, Erick L Ho, Amanda S Fang, Yuan Li, Isabella Tyler, Vincent Setola, Jason Aoto, Geoffrey W Abbott, Kevin T Beier","doi":"10.1016/j.neuron.2024.07.018","DOIUrl":"10.1016/j.neuron.2024.07.018","url":null,"abstract":"<p><p>The globus pallidus externus (GPe) is a central component of the basal ganglia circuit that acts as a gatekeeper of cocaine-induced behavioral plasticity. However, the molecular and circuit mechanisms underlying this function are unknown. Here, we show that GPe parvalbumin-positive (GPe<sup>PV</sup>) cells mediate cocaine responses by selectively modulating ventral tegmental area dopamine (VTA<sup>DA</sup>) cells projecting to the dorsomedial striatum (DMS). Interestingly, GPe<sup>PV</sup> cell activity in cocaine-naive mice is correlated with behavioral responses following cocaine, effectively predicting cocaine sensitivity. Expression of the voltage-gated potassium channels KCNQ3 and KCNQ5 that control intrinsic cellular excitability following cocaine was downregulated, contributing to the elevation in GPe<sup>PV</sup> cell excitability. Acutely activating channels containing KCNQ3 and/or KCNQ5 using the small molecule carnosic acid, a key psychoactive component of Salvia rosmarinus (rosemary) extract, reduced GPe<sup>PV</sup> cell excitability and impaired cocaine reward, sensitization, and volitional cocaine intake, indicating its therapeutic potential to counteract psychostimulant use disorder.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"3470-3485.e12"},"PeriodicalIF":14.7,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11502257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}