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

项目摘要 由前额叶皮质(PFC)控制的执行功能赋予我们行为的灵活性，并允许我们 在当前环境下做出适应性的行为。前额叶与背内侧核的功能相互作用 丘脑(MD)是丘脑的高级核团，已被证明对各种认知任务具有重要作用 需要行政控制。这两个相互连接的功能和解剖连接被破坏 在精神分裂症患者等临床人群中已经观察到了大脑区域。而一种地形 MDàPFC预测的组织已经跨物种被确定，关于如何改变 更广泛的MD-PFC电路的特定组件会导致某些认知缺陷。功能强大的 小鼠的分子和遗传工具现在使研究Defined的功能影响成为可能 大脑皮层处理的预测种群。特别是，不同的MD投射到 外侧眶前叶皮质(LOFC)尚未得到深入研究。LOFC被认为保持着一种认知 MAP--不同任务状态的表示--以确保在不同环境中进行自适应决策 由外部和内部变量决定。为了更好地了解MD是如何促成这一点的 大脑皮层功能、MDáLOFC预测种群和LOFC种群的实时活动模式将 在激励性学习任务中，使用纤维光度法在行为自由的小鼠中进行测量，这取决于 LOFC。这项技术将使我们能够研究MD和LOFC之间的功能关系 发生激励性的任务状态改变，并且当该任务状态改变通知控制 工具性行为。体外电生理学将用于研究MDàLOFC突触是如何 在激励学习中，传输可能会随着新任务状态的编码而改变。总而言之，建议的 实验将有助于确定MD在状态依赖期间影响LOFC活动的方式 决策，更广泛地说，它们将增加我们对高阶丘脑核团如何 对大脑皮层计算做出贡献。

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.