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: 8750984
• 负责人: Michael Goard
• 金额: $ 9万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8750984
• 关键词: Affect; Behavior; Behavioral; Brain; Calcium; Cations; Cognitive; 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; Process; 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; 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; public health relevance; relating to nervous system; response; spatiotemporal; therapeutic target; two-photon; visual stimulus

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.

描述（由申请人提供）：短期记忆，即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。与长期记忆不同的是，长期记忆涉及突触连接的改变，而短期记忆则与皮层和皮层下结构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