Gene Regulation in Memory Circuits as a Consequence of Polysubstance Use

多物质使用导致的记忆电路基因调控

基本信息

批准号：
10739399
负责人：
Karla R. Kaun
金额：
$ 51.29万
依托单位：
BROWN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-01 至 2028-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10739399
关键词：
Affect Alcohol consumption Alcohols Animals Behavior Behavioral Behavioral Assay Biological Assay Brain CREB1 gene Cells Chromatin Coupled Cues Drosophila genus Drosophila melanogaster Ethanol Functional Imaging Gene Expression Gene Expression Regulation Genes Genetic Transcription Goals Investigation Learning Legal Memory Methamphetamine Molecular Mushroom Bodies Neuronal Plasticity Neurons Nicotine Odors Pathway interactions Pharmaceutical Preparations Process Psychological reinforcement RNA Regulator Genes Role Self Administration Signal Pathway System Testing Transcriptional Regulation Volatilization Work Youth alcohol consequences approach behavior causal variant cocaine use drug of abuse drug seeking behavior experimental study fly gene discovery gene regulatory network individual variation innovation methamphetamine exposure methamphetamine use neural neurogenetics nicotine seeking behavior nicotine self-administration nicotine use opioid use polysubstance use preference psychostimulant response stimulant use synaptic function tool

项目摘要

PROJECT SUMMARY: Methamphetamine is a highly addictive drug that has major effects on the brain’s learning and memory systems. Methamphetamine use is commonly predicted by high use of legal psychostimulants such nicotine or alcohol, but the mechanisms underlying sequential use of alcohol, nicotine and methamphetamine are not well understood. Both nicotine and alcohol alter the function of brain circuits required for adaptive decisions, but the cellular and molecular mechanisms through which this occurs largely remain a mystery. Identifying the gene regulatory networks within select circuits in high alcohol or high nicotine seeking animals and deciphering how methamphetamine alters these networks is necessary to decode the fundamental molecular underpinnings through which methamphetamine influences maladaptive choice. However, the diversity of circuits and cells involved in these responses has confounded our ability to identify key molecular pathways. Our goal is to use a genes-circuits-behavior approach in Drosophila melanogaster to provide an innovative and holistic understanding of the core fundamental principles through which sequential use of psychostimulants alter the molecular landscape and neural dynamics of memory circuits to alter behavioral decisions. Transcriptional regulation within memory circuits is a fundamental process through which psychostimulants drive maladaptive changes in the brain function. This work provides the causal gene regulatory mechanisms through which high preference for alcohol or nicotine affects methamphetamine response in memory circuits. This has major implications for how co-use of psychostimulants alters the molecular landscape that drives drug-seeking behavior.

项目摘要：甲基苯丙胺是一种高度添加剂，对大脑的学习和记忆有重大影响系统。甲基苯丙胺的使用通常是通过大量使用尼古丁或酒精，但是酒精，尼古丁和甲基苯丙胺的顺序使用的机制不好理解。尼古丁和酒精都会改变自适应决策所需的脑电路的功能，但通过这种发生的细胞和分子机制在很大程度上仍然是一个谜。识别基因高酒精或高尼古丁寻求动物的选定电路中的监管网络，并破译甲基苯丙胺会改变这些网络对于解码基本分子基础所必需甲基苯丙胺会影响适应不良的选择。但是，电路和电池的多样性参与这些反应使我们识别关键分子途径的能力混淆了。我们的目标是使用果蝇中的基因循环 - 行为方法可提供创新和整体的了解核心基本原理，通过这种原则，顺序使用心理刺激因素改变了记忆电路的分子景观和神经动力学改变行为决策。转录记忆电路中的调节是一个基本过程大脑功能的变化。这项工作提供了因果基因调节机制，通过对酒精或尼古丁的偏爱会影响记忆电路中甲基苯丙胺的反应。这有专业对共同使用心理刺激剂的影响如何改变驱动吸毒的分子景观行为。