Functional architecture of the mediodorsal thalamus

内侧丘脑的功能结构

基本信息

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
项目类别：
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

项目摘要

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.

项目概要内侧丘脑 (MD) 及其与内侧前额叶皮层 (mPFC) 控制的相互联系该神经回路的功能障碍可能会导致执行功能和社会行为的重要方面。了解大脑发育障碍和神经精神疾病。 (MD→mPFC) 电路功能因缺乏对 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的中心假设是内在的差异。为神经元提供上升输入的两个主要神经元群之间的属性和连接性 mPFC 使它们提取并向 mPFC 传输不同的信息，因此，这两个群体。在行为中发挥不同的作用，总体目标是扩大对 MD 内电路的理解。基本原理是，对丘脑和丘脑输入到前额皮质的神经处理的理解是对于理解执行功能的机制和开发神经调节疗法是必要的针对神经精神疾病的前额叶网络将通过三个方面进行检验。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 神经元如何差异化处理来自不同大脑区域的突触输入 3) 确定。特定 MD 回路的光遗传学操作如何影响认知、社交和情感行为野生型小鼠。申请人认为，本申请中提出的研究具有创新性，因为它定义了尚未研究但必不可少的丘脑核的功能，从膜生物物理学水平到突触这项工作意义重大，因为它将有助于解剖学和行为学的研究。最终，这些知识有可能指导前额丘脑皮质回路的生理图。开发未来的神经调节策略来治疗神经精神疾病的症状定位到前额叶网络。