The Role of Sensory Inputs and Cholinergic Modulation for the Coding of Location and Movement Speed in the Entorhinal Cortex

感觉输入和胆碱能调节在内嗅皮层位置和运动速度编码中的作用

• 批准号: 10561681
• 负责人: Holger Dannenberg
• 金额: $ 37.6万
• 依托单位: GEORGE MASON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10561681
• 关键词: Acetylcholine; Address; Affect; Animals; Anxiety; Attention; Auditory; Behavior; Cells; Code; Cognitive; Computer Models; Cues; Darkness; Data; Data Science; Detection; Development; Diagonal Band of Broca; Fiber; Foundations; Frequencies; Future; Goals; Grant; Light; Link; Location; Major Depressive Disorder; Maps; Medial; Memory; Memory impairment; Mental Depression; Mental disorders; Mission; Modality; Modeling; Monitor; Movement; Mus; National Institute of Mental Health; Neuromodulator; Neurons; Outcome; Pattern; Periodicals; Periodicity; Phase; Photometry; Process; Public Health; Research; Research Personnel; Retrieval; Rodent; Role; Running; Schizophrenia; Sensory; Short-Term Memory; Signal Transduction; Speed; Testing; Time; Training; Update; Vision; Visual; Work; cholinergic; cognitive function; cognitive process; entorhinal cortex; experimental study; innovation; millisecond; network models; neural; neuronal circuitry; neuroregulation; optogenetics; preservation; response; sensory input; skills; spatial memory

PROJECT SUMMARY/ABSTRACT The goal of this project is to investigate potential mechanistic roles of sensory inputs and cholinergic modulation for generating neural coding of location and movement speed. The results are expected to support development of models of network mechanisms underlying psychiatric disorders. Representations for spatial location and movement speed are important for path integration and memory-guided navigation. Recordings of grid cells and theta oscillations in the medial entorhinal cortex in freely exploring mice under conditions of light and complete darkness will first address the question how long the neuronal code for location by grid cell firing and the code for movement speed by theta frequency are preserved in working memory in the absence of visual inputs. Analysis of the acquired data will test the hypothesis that changes in spatial periodic grid cell firing correlate in time with changes in the theta frequency vs. running speed relationship. The expected outcomes of these analyses will be used to inform computational models of path integration, including models of grid cell firing. Experiments under Specific Aim #2 will use fiber photometry for monitoring cholinergic activity in the medial entorhinal cortex to address the role of cholinergic modulation in forming and preserving codes for location and movement speed in the presence and absence of visual cues. Analyses will test if changes in sensory inputs, neuronal activity, and cholinergic modulation correlate at different time scales. These analyses will further our mechanistic understanding of coding principles underlying a broad range of cognitive processes associated with spatial memory. Both grid cells and cholinergic modulation are essential in current models of spatial memory and memory-guided navigation. Experiments under Specific Aim #3 will use optogenetic inhibition of cholinergic projection neurons in the medial septum in combination with grid cell recordings in the medial entorhinal cortex to test the hypothesis that cholinergic signaling is necessary for spatial periodic firing of grid cells. Finally, experiments under Specific Aim #4 will investigate if auditory and olfactory cues are sufficient to support the formation of a cognitive spatial map by grid cell firing in the medial entorhinal cortex. Simultaneous recording of grid cells in the medial entorhinal cortex and monitoring of cholinergic activity by fiber photometry in complete darkness during the presence or absence of auditory or olfactory cues will test the hypotheses that auditory and olfactory inputs in isolation can be used to form a cognitive map that supports path integration and that cholinergic modulation supports memory-guided navigation based on these maps. The experimental and computational skills developed during the training period of this project and the additional theoretical training in neural data science and computational modeling will be crucial for the accomplishment of the proposed short- and long-term scientific goals and will become the foundation for the future work as an independent researcher.

项目总结/摘要 本项目的目标是研究感觉输入和胆碱能神经的潜在机制作用。 用于产生位置和运动速度的神经编码的调制。预计结果将支持 开发精神疾病的网络机制模型。空间表示 位置和移动速度对于路径整合和存储器引导的导航是重要的。录音 光照条件下自由探索小鼠内侧内嗅皮层的网格细胞和θ振荡 完全的黑暗将首先解决这个问题， 和由θ频率表示的运动速度的代码被保存在工作记忆中， 视觉输入对采集数据的分析将检验空间周期性网格单元变化的假设 点火在时间上与θ频率对运行速度关系的变化相关。预期 这些分析的结果将用于为路径整合的计算模型提供信息，包括模型 网格细胞放电。具体目标2下的实验将使用纤维光度法监测胆碱能活性 在内侧内嗅皮层，以解决胆碱能调制在形成和保存代码中的作用 在有和没有视觉提示的情况下的位置和移动速度。分析将测试 感觉输入、神经元活动和胆碱能调节在不同的时间尺度上相关。这些分析 将进一步加深我们对广泛认知过程中编码原则的机械理解 与空间记忆有关。网格细胞和胆碱能调节在目前的模型中是必不可少的。 空间记忆和记忆引导导航。具体目标#3下的实验将使用光遗传学 内侧隔胆碱能投射神经元的抑制与脑内网格细胞记录相结合 内侧内嗅皮层，以检验胆碱能信号是空间周期性放电所必需的假设 网格细胞。最后，具体目标#4下的实验将调查听觉和嗅觉线索是否 足以支持通过内侧内嗅皮层中的网格细胞放电形成认知空间图。 同步记录内侧内嗅皮层网格细胞和监测胆碱能活动 在完全黑暗中，在存在或不存在听觉或嗅觉线索的情况下，纤维光度法将测试 假设听觉和嗅觉输入可以单独用于形成认知图， 路径整合和胆碱能调节支持基于这些地图的记忆引导导航。 本项目培训期间开发的实验和计算技能以及 神经数据科学和计算建模方面的额外理论培训将对 实现所提出的短期和长期科学目标，并将成为 未来的工作作为一个独立的研究员。