Dissection of the neural circuitry of short-term memory in behaving mice

描述（由申请人提供）：短期记忆，在短时间内记住信息的能力，是一系列复杂能力的基础认知过程。与涉及突触连接的修改的长期记忆相反，短期记忆与皮质和皮质下结构中的持续神经活动有关。特别是，最近的研究表明，后顶叶皮层起着重要的作用。 在保持记忆痕迹中的关键作用。然而，目前还不清楚这些区域的神经活动如何支持短期记忆的维持。该项目的目标是为头部固定的小鼠开发短期记忆任务，并利用双光子钙成像和光遗传学的最新进展来解剖短期记忆的神经回路。（目的1）开发小鼠的短期记忆任务，并使用双光子钙成像测量视觉和顶叶皮质中短期记忆的神经特征。(Aim 2）使用靶向光遗传学失活确定特定皮质区域中持续活性的必要性和时程。(Aim 3a）通过去甲肾上腺素能张力的光遗传学调节来研究去甲肾上腺素在短期记忆任务期间对持续皮质活动的作用。(Aim 3b）确定短期记忆维持的持续时间和准确性是否可以通过去甲肾上腺素释放的光遗传学调节来改善。发展对短期记忆的系统水平的理解将对大脑如何表示和维护信息产生重要的见解，并可能对治疗正常衰老和精神疾病中常见的短期记忆缺陷具有翻译意义。

DESCRIPTION (provided by applicant): Short-term memory, the ability to hold information in mind over short timescales, is a fundamental cognitive process underlying an array of complex abilities. In contrast to long-term memory, which involves modification of synaptic connections, short-term memory is associated with sustained neural activity in cortical and subcortical structures. In particular, recent studies have suggested that the posterior parietal cortex plays a key role in maintaining mnemonic traces. However, it is not understood how the neural activity in these regions supports the maintenance of short-term memory. The goal of this project is to develop a short-term memory task for head-fixed mice and to leverage recent advances in 2-photon calcium imaging and optogenetics to dissect the neural circuits underlying short-term memory. This goal will be undertaken with the following aims: (Aim 1) Develop a short-term memory task for mice, and measure the neural signature of short-term memory in visual and parietal cortices using 2-photon calcium imaging. (Aim 2) Determine the necessity and time course of sustained activity in specific cortical regions using targeted optogenetic inactivation. (Aim 3a) Investigate the role of norepinephrine on sustained cortical activity during the short-term memory task by optogenetic modulation of noradrenergic tone. (Aim 3b) Determine whether the duration and accuracy of short-term memory maintenance can be improved by optogenetic modulation of norepinephrine release. Developing a systems-level understanding of short-term memory will yield critical insights into how the brain represents and maintains information, and may have translational implications for treating deficits in short-term memory commonly observed in normal aging and psychiatric disorders.