Neural circuit mechanisms underlying cognitive control of sensory-guided behavior

感觉引导行为认知控制的神经回路机制

• 批准号: 10708094
• 负责人: David J Margolis
• 金额: $ 37.88万
• 依托单位: RUTGERS, THE STATE UNIV OF N.J.
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-15 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10708094
• 关键词: Address; Anatomy; Area; Behavior; Behavior Control; Behavioral; Behavioral Mechanisms; Brain; Cell Nucleus; Cells; Chronic; Color; Corpus striatum structure; Discrimination; Dorsal; Electrophysiology (science); Fiber; Gilles de la Tourette syndrome; Goals; Huntington Disease; Image; Impairment; Impulsive Behavior; Impulsivity; Interneurons; Knowledge; Learning; Measurement; Measures; Medial; Medial Dorsal Nucleus; Mediating; Modeling; Motor; Mus; Neocortex; Neural Pathways; Neurons; Obsessive-Compulsive Disorder; Parvalbumins; Pathway interactions; Pattern; Performance; Photometry; Play; Population; Population Dynamics; Role; Sensory; Shapes; Signal Transduction; Site; Slice; Somatosensory Cortex; Synapses; Synaptic plasticity; System; Tactile; Task Performances; Testing; Texture; Thalamic Nuclei; Thalamic structure; Touch sensation; Vibrissae; Work; behavior influence; behavioral response; cell type; cognitive control; experimental study; in vivo; in vivo imaging; learned behavior; mouse model; neocortical; nerve supply; nervous system disorder; neural; neural circuit; optogenetics; patch clamp; response; two-photon

SUMMARY The ability to make appropriate actions, as well as to inhibit unbeneficial actions, is a key aspect of sensorimotor learning. Our recent work has used the mouse whisker system as model for sensory-guided learning to identify an important and previously unknown role for synaptic input from primary somatosensory cortex (S1) to the dorsal striatum (DStr) as a substrate for response inhibition. This renewal proposal aims to test the idea that the relative synaptic innervation of striatal parvalbumin-expressing (PV) interneurons compared to the spiny projection neurons (SPNs) is a circuit mechanism for behavioral response inhibition. We will use a suite of in vivo imaging and optogenetics experiments, as well as ex vivo electrophysiology experiments to measure and manipulate neural circuitry from two important brain areas: S1 and thalamic posterior medial nucleus (POm) to test their roles in modulation of DStr. Preliminary results suggest that S1 and POm influence behavioral performance of a texture discrimination task in opposing ways, allowing for focused tests of our hypotheses of the synaptic circuitry mediating these learned behaviors. Our integrative in vivo and ex vivo approach, combining manipulation of specific neural pathways, longitudinal tracking of genetically identified neurons, anatomical analysis, and ex vivo synaptic measurements will allow us to investigate the neural circuit basis of learned response inhibition at a scale not before achieved. A major goal is to address the gap in knowledge on the roles of S1 and POm projections to the striatum and their influence on behavior. The results will have implications for the neural circuitry underlying cognitive control, which will aid our understanding the basis of neurological disorders involving deficits in cognitive control.

总结 做出适当动作的能力，以及抑制不利动作的能力，是感觉运动的一个关键方面。 学习我们最近的工作已经使用了鼠标胡须系统作为模型的感觉引导学习，以识别 一个重要的和以前未知的作用，突触输入从初级躯体感觉皮层（S1）到 背侧纹状体（DStr）作为反应抑制的底物。这一更新建议旨在测试以下想法： 纹状体小白蛋白表达（PV）的中间神经元与棘状突起相比的相对突触神经支配 投射神经元（SPNs）是行为反应抑制的回路机制。我们将使用一套在 体内成像和光遗传学实验，以及离体电生理学实验，以测量和 从两个重要的大脑区域操纵神经回路：S1和丘脑后内侧核（POm）， 测试它们在DStr调节中的作用。初步结果表明，S1和POM影响行为 以相反的方式执行纹理辨别任务，允许对我们的假设进行集中测试， 调节这些习得行为的突触回路。我们的综合体内和体外方法，结合 操纵特定的神经通路，纵向跟踪遗传识别的神经元，解剖 分析和离体突触测量将使我们能够研究学习的神经回路基础。 反应抑制在以前没有达到的规模。一个主要的目标是解决对这些角色的认识上的差距 S1和POm投射到纹状体及其对行为的影响。研究结果将对 认知控制背后的神经回路，这将有助于我们理解神经系统的基础。 涉及认知控制缺陷的疾病。

项目成果

Role of Posterior Medial Thalamus in the Modulation of Striatal Circuitry and Choice Behavior.

后内侧丘脑在纹状体回路和选择行为调节中的作用。

• DOI: 10.1101/2024.03.21.586152
• 发表时间: 2024
• 期刊: bioRxiv : the preprint server for biology
• 作者: Yonk,AlexJ;Linares-García,Ivan;Pasternak,Logan;Juliani,SofiaE;Gradwell,MarkA;George,ArleneJ;Margolis,DavidJ
• 通讯作者: Margolis,DavidJ

Pupil Dynamics Reflect Behavioral Choice and Learning in a Go/NoGo Tactile Decision-Making Task in Mice.

• DOI: 10.3389/fnbeh.2016.00200
• 发表时间: 2016
• 期刊: Frontiers in behavioral neuroscience
• 影响因子: 3
• 作者: Lee CR;Margolis DJ
• 通讯作者: Margolis DJ

An Optical Exposé of Cortical Function.

皮质功能的光学暴露。

• DOI: 10.1016/j.tins.2019.05.003
• 发表时间: 2019
• 期刊: Trends in neurosciences
• 影响因子: 15.9
• 作者: Shvedov,Naomi;Margolis,DavidJ
• 通讯作者: Margolis,DavidJ

Aberrant Cortical Activity in Multiple GCaMP6-Expressing Transgenic Mouse Lines.

• DOI: 10.1523/eneuro.0207-17.2017
• 发表时间: 2017-09
• 期刊: eNeuro
• 影响因子: 3.4
• 作者: Steinmetz NA;Buetfering C;Lecoq J;Lee CR;Peters AJ;Jacobs EAK;Coen P;Ollerenshaw DR;Valley MT;de Vries SEJ;Garrett M;Zhuang J;Groblewski PA;Manavi S;Miles J;White C;Lee E;Griffin F;Larkin JD;Roll K;Cross S;Nguyen TV;Larsen R;Pendergraft J;Daigle T;Tasic B;Thompson CL;Waters J;Olsen S;Margolis DJ;Zeng H;Hausser M;Carandini M;Harris KD
• 通讯作者: Harris KD

FosGFP expression does not capture a sensory learning-related engram in superficial layers of mouse barrel cortex

• DOI: 10.1073/pnas.2112212118
• 发表时间: 2021-12-28
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Lee, Jiseok;Urban-Ciecko, Joanna;Barth, Alison L.
• 通讯作者: Barth, Alison L.