Functional architecture of the mediodorsal thalamus

项目摘要 丘脑内侧背侧及其与内侧前额叶皮质的相互联系 行政职能和社会行为的重要方面。这种神经回路的功能障碍可能会导致 发育性大脑障碍和神经精神疾病。了解前额叶丘脑皮质 由于缺乏对MD投射神经元类型的了解，MD→mPFC的电路功能受到阻碍 以及它们如何整合和处理突触信息。中心假说是内在的差异 两个主要神经元群体之间的属性和连通性，它们为 MPFC使它们提取不同的信息并将其发送到mPFC。因此，这两个群体 在行为中扮演不同的角色。总体目标是扩大对MD内部电路的理解。这个 基本原理是，通过丘脑和丘脑对前额叶皮质的输入理解神经处理是 了解执行功能的机制和开发神经调节疗法所必需的 针对神经精神障碍的前额叶网络。核心假设将通过三个方面进行检验 具体目的：1)确定MD神经元的固有特性如何控制mPFC输入的突触整合。 2)测试MD神经元如何不同地处理来自不同大脑区域的突触输入。3)确定 特定MD回路的光基因操作如何影响认知、社交和情感行为 野生型老鼠。 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 从膜生物物理学水平到突触的未被充分研究的基本丘脑核团的功能 整合，以控制行为。这项工作意义重大，因为它将对解剖学和 前额叶丘脑皮质回路的生理图。归根结底，这样的知识有可能指导 未来治疗神经精神障碍症状的神经调节策略的发展 定位到前额叶网络。

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.