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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.

精神活性药物和解离性药物，如氯胺酮、摇头丸和甲基苯丙胺，通过诱导大脑状态的深刻改变而产生的心理影响。这些药物的流行，心理和生理上的成瘾性，以及它们作为潜在治疗剂的日益流行表明迫切需要了解精神活性和解离性药物对患者的急性和长期影响，大脑状态然而，在我们对药物改变的潜在电路机制的理解中存在很大的差距。国家自己。为了弥合这一差距，我们试图阐明分子，电路和网络机制，药物诱导的认知状态，利用明确的海马旁微电路。神经空间表示的基础部分取决于海马旁皮质的神经回路，该回路将外部环境转化为支持空间导航和记忆的内部空间地图。我们的初步数据表明氯胺酮和甲基苯丙胺给药对海马旁回路编码，其特征在于具有高度易处理的响应特性的细胞和明确的行为相关性在这里，我们使用高度跨学科的方法，结合体内电生理学与计算建模，成像和行为技术，以检查之间的联系，药物引起的神经认知效应以及空间和记忆编码的微电路。首先，我们将联合收割机体内生理，计算和成像方法，以阐明是否微电路的影响，氯胺酮反映了一种改变的感官体验或内部计算的变化，地图接下来，我们使用高密度的体内电生理学和行为范例来确定电路以及用于编码精神活性药物相关目标、空间线索和复发触发的网络机制。最后，将在体电生理学与帧投射独立纤维光度学相结合， MDMA亲社会效应的电路基础结合起来，这些研究将提供重要的见解，通过利用我们对高阶神经代码的理解，对记忆和自我定位的认知过程至关重要的皮层区域。