Project 2

项目2

基本信息

批准号：
9358982
负责人：
Lisa Giocomo
金额：
$ 25.94万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-15 至 2022-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9358982
关键词：
Acute Behavioral Behavioral Paradigm Brain Brain region Cells Chronic Code Cognition Cognitive Collaborations Computer Simulation Cues Data Dissociation Electroencephalography Electrophysiology (science)Environment Episodic memory Fiber Frequencies Goals Hallucinations Hippocampus (Brain)Human Image Infusion procedures Investigation Ketamine Light Link Locales Long-Term Effects Maps Measures Medial Memory Methamphetamine Molecular Nature Neurocognitive Neurons Perception Pharmaceutical Preparations Photometry Physiological Play Prevalence Property Psychotropic Drugs Relapse Role Sensory Shapes Social Environment Space Perception Techniques Therapeutic Agents Time Translating Translations cognitive process density drug action drug of abuse drug seeking behavior ecstasy entorhinal cortex experience imaging approach in vivo insight interdisciplinary approach memory encoding memory process molecular dynamics multisensory neural circuit non-drug preference psychologic relating to nervous system response social spatial memory two-photon way finding

项目摘要

Psychoactive and dissociative drugs, such as ketamine, MDMA and methamphetamine, exert powerful psychological effects by inducing profoundly altered brain states. The popularity of these drugs, their psychologically and physiologically addictive nature and their rising prevalence as potential therapeutic agents indicate an urgent need to understand the acute and long-term effects of psychoactive and dissociative drugs on brain-states. A large gap exists however, in our understanding of the circuit mechanisms underlying drug-altered states themselves. To bridge this gap, we seek to elucidate the molecular, circuit and network mechanisms of drug induced cognitive states by taking advantage of the well-defined parahippocampal microcircuit. The neural basis for the representation of space depends, in part, on neural circuits in the parahippocampal cortex, which translate the external environment into an internal map of space that supports spatial navigation and memory. Our preliminary data points to significant effects of ketamine and methamphetamine administration on parahippocampal circuit codes, which are characterized by cells with highly tractable response properties and a clear behavioral relevance. Here, we use a highly interdisciplinary approach that combines in vivo electrophysiology with computational modeling, imaging and behavioral techniques to examine the link between drug-induced neurocognitive effects and the microcircuits of spatial and memory coding. First, we combine in vivo physiological, computational and imaging approaches to elucidate whether the microcircuit effects of ketamine reflect an altered sensory experience or a change in the internal computations that generate spatial maps. Next, we use high-density in vivo electrophysiology and behavioral paradigms to determine the circuit and network mechanisms for encoding psychoactive drug associated goals, spatial cues and relapse triggers. Finally, in vivo electrophysiology is combined with frame-projected independent-fiber photometry to parse out the circuit basis of MDMA’s pro-social effects. Combined, these studies will provide important insights into the circuit underpinnings of drug-induced states by leveraging our understanding of the neural codes in a high-order cortical region crucial to the cognitive processes of memory and self-localization.

精神活性和分离药物，例如氯胺酮，MDMA和甲基苯丙胺，发挥强大诱发的大脑状态的心理影响。这些药物的普及作为潜在治疗剂的心理和身体上的添加性质及其上升的患病率表明迫切需要了解精神活性和分离药物对脑状态。但是，存在很大的差距，在我们对改变药物的电路机制的理解中国家自己。为了弥合这一差距，我们寻求阐明分子，电路和网络机制药物通过利用定义明确的帕拉希普门户微电路来诱导认知态。神经代表空间的基础部分取决于帕拉希普省皮质中的神经电路将外部环境转换为支持空间导航和内存的空间内部图。我们的初步数据指出氯胺酮和甲基苯丙胺对 Parahampocampal电路代码，其特征是具有高度可触发响应特性的细胞和A 明确的行为相关性。在这里，我们使用一种将体内结合的高度跨学科方法用计算建模，成像和行为技术的电生理学检查药物诱导的神经认知效应以及空间和记忆编码的微电路。首先，我们合并体内生理，计算和成像方法，以阐明微电路的影响是否影响氯胺酮反映了改变的感觉体验或内部计算的变化地图。接下来，我们使用体内电生理学和行为范式的高密度来确定电路以及编码精神活性药物相关目标，空间提示和继电器触发器的网络机制。最后，将体内电生理学与框架预测的独立纤维光度法结合在一起，以解析 MDMA的促进效应的电路基础。这些研究结合在一起，将为您提供重要的见解通过利用我们对高阶神经元代码的理解，药物诱导状态的电路基础皮质区域对记忆和自定位的认知过程至关重要。