The Functional Role of Mediodorsal Thalamic Input onto the Mouse Lateral Orbitofrontal Cortex in Incentive Learning

小鼠外侧眶额皮层内侧丘脑输入在激励学习中的功能作用

• 批准号: 9760816
• 负责人: Ege Ayse Yalcinbas
• 金额: $ 3.79万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-01 至 2022-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9760816
• 关键词: Affect; Anatomy; Area; Attenuated; Behavior; Brain region; Cells; Clinical; Cognitive; Cognitive deficits; Decision Making; Dorsal; Electrophysiology (science); Ensure; Environment; Feedback; Fiber; Fluorescence; Functional disorder; Grant; Image; Impairment; Implant; Incentives; Interneurons; Investigation; Label; Lateral; Lead; Learning; Light; Maps; Measures; Medial; Mediating; Methods; Molecular Genetics; Motivation; Mus; Neurons; Outcome; Parvalbumins; Patients; Pattern; Photometry; Physiologic pulse; Physiology; Population; Population Projection; Prefrontal Cortex; Protocols documentation; Reporter; Research; Role; Schizophrenia; Specificity; Synapses; Synaptic Transmission; Techniques; Testing; Thalamic Nuclei; Thalamic structure; Thinking; Time; Transgenic Mice; Update; Viral Vector; Virus; Work; autism spectrum disorder; base; calcium indicator; cell type; cognitive task; designer receptors exclusively activated by designer drugs; executive function; experimental study; flexibility; in vivo; intersectionality; neuropsychiatric disorder; neuropsychiatry; optical fiber; optogenetics; postsynaptic; presynaptic; relating to nervous system; tool; voltage; voltage clamp

Project Summary Executive functions controlled by the prefrontal cortex (PFC) grant us flexibility in our behavior and allow us to behave adaptively in the current context. The functional interaction between the PFC and the mediodorsal thalamus (MD), a higher-order thalamic nucleus, has been shown to be important for a variety of cognitive tasks requiring executive control. Disrupted functional and anatomical connectivity of these two reciprocally connected brain regions has been observed in clinical populations such as schizophrenia patients. While a topographic organization of MDàPFC projections has been identified across species, little is known about how changes in specific components of the broader MD-PFC circuitry lead to certain cognitive deficits. The availability of powerful molecular and genetic tools in mice has now made it possible to study the functional influence of defined projection populations on cortical processing. In particular, the functional role of distinct MD projections onto the lateral orbitofrontal cortex (lOFC) has yet to be investigated in depth. The lOFC is thought to maintain a cognitive map -- a representation of different task states -- in order to ensure adaptive decision-making in different contexts determined by external and internal variables. To better understand how the MD may be contributing to this cortical function, real-time activity patterns of the MDàlOFC projection population and the lOFC population will be measured using fiber photometry in freely behaving mice, during an incentive learning task that depends on the lOFC. This technique will allow us to study the functional relationship between the MD and lOFC when a motivationally-induced task state change occurs, and when this task state change informs the control of instrumental behavior. Ex vivo electrophysiology will be used to investigate how MDàlOFC synaptic transmission may change following the encoding of a new task state in incentive learning. Together, the proposed experiments will help determine the manner in which the MD influences lOFC activity during state-dependent decision-making, and more generally, they will add to our understanding of how higher-order thalamic nuclei contribute to cortical computations.

项目摘要 由前额叶皮层（PFC）控制的执行功能赋予我们行为的灵活性，并允许我们 在当前上下文中自适应地行为。前额叶皮层和背内侧核之间的功能相互作用 丘脑（MD）是丘脑的一个高级核团，在多种认知活动中起重要作用 需要执行控制。破坏了这两个连接的神经元的功能和解剖连接 已经在临床人群如精神分裂症患者中观察到脑区域。虽然地形 MDàPFC预测的组织已经在物种间得到了确定，但对物种的变化知之甚少。 更广泛的MD-PFC电路的特定组件导致某些认知缺陷。强大的可用性 在小鼠中的分子和遗传工具现在使得研究定义的功能影响成为可能。 投射群体对皮层处理的影响特别是，不同的MD投射到 外侧眶额皮质（IOFC）尚未被深入研究。IOFC被认为保持认知 地图--不同任务状态的表示--以确保在不同情况下做出适应性决策 由外部和内部变量决定。为了更好地了解MD如何对此做出贡献， 皮质功能，MDà 1 OFC投射群体和IOFC群体的实时活动模式将 在自由行为的小鼠中，在依赖于以下因素的激励学习任务期间， IOFC。这种技术将允许我们研究当一个特定的时间点时MD和IOFC之间的函数关系。 动机引起的任务状态变化发生，并且当该任务状态变化通知控制器 工具性行为离体电生理学将用于研究MDà 1 OFC突触如何在体外被激活。 在激励学习中，传输可以随着新任务状态的编码而改变。在一起，拟议的 实验将有助于确定MD在依赖于状态的过程中影响IOFC活动的方式。 决策，更普遍地说，它们将增加我们对高级丘脑核团如何 有助于大脑皮层的计算