Functional architecture of the mediodorsal thalamus

内侧丘脑的功能结构

• 批准号: 10571113
• 负责人: Audrey Christine Brumback
• 金额: $ 78.73万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-12-06 至 2025-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10571113
• 关键词: Action Potentials; Acute; Affect; Affective; Amygdaloid structure; Anatomy; Anterior; Anxiety; Architecture; Behavior; Behavior Control; Biological Assay; Biology; Biophysics; Brain; Brain Diseases; Brain region; Cations; Cerebellum; Cognitive; Cognitive Therapy; Color; Complex; Coupled; Cyclic Nucleotides; Data; Development; Disease; Electrophysiology (science); Emotional; Foundations; Future; Goals; Grant; Heart; Individual; Injections; Insula of Reil; Knowledge; Lateral; Lesion; Maps; Measures; Medial; Medical; Membrane; Membrane Potentials; Memory; Modeling; Morphology; Mus; Neurobiology; Neurodevelopmental Disorder; Neuronal Dysfunction; Neurons; Output; Pathway interactions; Pharmacology; Physiological; Physiology; Population; Prefrontal Cortex; Process; Property; Research; Resistance; Role; Schizophrenia; Short-Term Memory; Slice; Social Behavior; Social Controls; Social Functioning; Source; Structure; Symptoms; Synapses; Testing; Thalamic Nuclei; Thalamic structure; Time; Wild Type Mouse; Work; anxiety-like behavior; avoidance behavior; behavior influence; cell cortex; cognitive control; emotional functioning; emotional symptom; executive function; expectation; experimental study; in vivo; individuals with autism spectrum disorder; innovation; neural; neural circuit; neurobiological mechanism; neuropsychiatric disorder; neuropsychiatry; neuroregulation; optogenetics; patch clamp; response; social; social anxiety; superior colliculus Corpora quadrigemina; symptom treatment; targeted treatment; therapy development; transmission process

PROJECT SUMMARY The mediodorsal thalamus (MD) and its reciprocal connection with medial prefrontal cortex (mPFC) control important aspects of executive functioning and social behavior. Dysfunction of this neural circuit can cause developmental brain disorders and neuropsychiatric conditions. Understanding prefrontal thalamocortical (MD→mPFC) circuit function has been hampered by a lack of understanding of MD projection neuron types and how they integrate and process synaptic information. The central hypothesis is that differences in intrinsic properties and connectivity between the two major populations of neurons that provide ascending input to the mPFC causes them to extract and transmit different information to the mPFC. Thus, these two populations have different roles in behavior. The overall goal is to expand understanding of the circuits within MD. The rationale is that understanding of neural processing by the thalamus and thalamic inputs to prefrontal cortex is necessary for understanding the mechanisms of executive function and developing neuromodulation therapies targeting the prefrontal network for neuropsychiatric disorders. The central hypothesis will be tested with three specific aims: 1) Determine how intrinsic properties of MD neurons control synaptic integration of mPFC inputs. 2) Test how MD neurons differentially process synaptic inputs arising from different brain regions. 3) Determine how optogenetic manipulation of specific MD circuits affects cognitive, social, and affective behaviors in wildtype mice. The research proposed in this application is innovative, in the applicant's opinion, because it defines the function of an understudied but essential thalamic nucleus, from the level of membrane biophysics, to synaptic integration, to control of behavior. The work is significant because it will contribute to the anatomical and physiological map of prefrontal thalamocortical circuitry. Ultimately, such knowledge has the potential to guide the development of future neuromodulation strategies to treat the symptoms of neuropsychiatric disorders that localize to the prefrontal network.

项目摘要 内侧背丘脑及其与内侧前额叶皮层控制的相互联系 执行功能和社会行为的重要方面。这种神经回路的功能失调会导致 发育性脑障碍和神经精神疾病。了解前额叶丘脑皮质 (MD→mPFC）回路功能由于缺乏对MD投射神经元类型的了解而受到阻碍 以及它们如何整合和处理突触信息。核心假设是， 提供上行输入的两个主要神经元群体之间的属性和连通性。 mPFC使它们提取并向mPFC传输不同的信息。因此，这两个群体 在行为中扮演着不同的角色。总体目标是扩大对MD内电路的理解。的 基本原理是，理解丘脑和丘脑输入到前额叶皮层的神经处理， 理解执行功能的机制和开发神经调节疗法所必需的 针对前额叶网络的神经精神疾病。中心假设将用三个 具体目标：1）确定MD神经元的内在特性如何控制mPFC输入的突触整合。 2)测试MD神经元如何区别处理来自不同大脑区域的突触输入。3)确定 特定MD电路的光遗传学操作如何影响认知，社会和情感行为， 野生型小鼠 在申请人看来，本申请中提出的研究是创新的，因为它定义了 从膜生物物理学的水平，到突触的水平， 整合，控制行为。这项工作是重要的，因为它将有助于解剖和 前额叶丘脑皮层回路的生理图最终，这些知识有可能指导 未来神经调节策略的发展，以治疗神经精神疾病的症状， 定位到前额网络。