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

行为小鼠短期记忆神经回路的剖析

• 批准号: 9177784
• 负责人: Michael Goard
• 金额: $ 24.9万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-02-08 至 2019-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9177784
• 关键词: Affect; Behavior; Behavioral; Brain; Calcium; Cations; Complex; Data; Dissection; Dopamine; Exhibits; Feedback; Goals; Head; Image; Information Theory; Learning; Light; Maintenance; Measurement; Measures; Mental disorders; Mind; Modification; Mus; Neuromodulator; Neurons; Norepinephrine; Parietal; Parietal Lobe; Performance; Play; Recurrence; Research; Role; Short-Term Memory; Specificity; Stimulus; Structure; Synapses; System; Task Performances; Testing; Time; Tissues; Training; Transgenic Mice; Viral; Visual; Visual Cortex; base; calcium indicator; cognitive process; excitatory neuron; frontal lobe; improved; inhibitory neuron; insight; light gated; locus ceruleus structure; long term memory; neural circuit; nonhuman primate; noradrenergic; normal aging; novel; optogenetics; relating to nervous system; response; spatiotemporal; therapeutic target; two-photon; visual stimulus

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.

短期记忆，即在短时间内将信息保持在脑海中的能力，是一种基本的认知能力， 一系列复杂能力背后的过程。与长期记忆相反，长期记忆涉及修改 在突触连接中，短期记忆与皮层和皮层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 保持记忆痕迹的作用。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。这个项目的目标是培养短期记忆 任务，并利用双光子钙成像和光遗传学的最新进展， 剖析短期记忆的神经回路实现这一目标的目标如下： (Aim 1）为小鼠开发短期记忆任务，并测量短期记忆的神经特征 在视觉和顶叶皮质中使用双光子钙成像。(Aim 2）确定必要性和时间 使用靶向光遗传学失活在特定皮质区域中持续活动的过程。(Aim 3a） 研究去甲肾上腺素在短时记忆任务中对持续皮层活动的作用， 去甲肾上腺素能紧张的光遗传学调节。(Aim 3b）确定是否持续时间和准确性 通过去甲肾上腺素释放的光遗传学调节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 代表和维持信息，并可能对短期治疗缺陷有翻译意义。 在正常衰老和精神疾病中常见的记忆。