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

短期记忆，即在短时间内记住信息的能力，是一种基本的认知能力 一系列复杂能力背后的过程。与长期记忆不同，长期记忆涉及修改 在突触连接中，短期记忆与大脑皮层和大脑皮质中持续的神经活动有关 皮质下结构。特别是，最近的研究表明，后顶叶皮质起着关键作用 在保持记忆痕迹方面的作用。然而，目前还不清楚这些区域的神经活动是如何 支持短期记忆的维持。这个项目的目标是发展一种短期记忆 头固定小鼠的任务和利用双光子钙成像和光遗传学的最新进展 剖析短期记忆背后的神经回路。实现这一目标的目的如下： (目的1)开发小鼠短期记忆任务，测量小鼠短期记忆的神经特征 在视觉和顶叶皮质使用双光子钙成像。(目标2)确定必要性和时间 在特定的皮质区域使用定向光遗传失活的持续活动的过程。(目标3a) 研究去甲肾上腺素在短期记忆任务中持续皮质活动中的作用 去甲肾上腺素能张力的光遗传调控。(目标3b)确定是否持续时间和准确性 通过光遗传调控去甲肾上腺素的释放，可以改善短期记忆维持。 发展对短期记忆的系统水平的理解将产生对大脑如何 代表和维护信息，并可能对短期内处理赤字产生翻译影响 在正常衰老和精神障碍中常见的记忆。

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 norepinephine 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.