Neurotransmitter Switching and Its Function in Hippocampal Plasticity

神经递质转换及其在海马可塑性中的作用

• 批准号: 8806924
• 负责人: NICHOLAS CANADAY SPITZER
• 金额: $ 18.32万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-10 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8806924
• 关键词: Address; Adult; Animal Behavior; Appearance; Automobile Driving; Behavior; Biological Neural Networks; Brain; Cells; Chronic stress; Dependence; Development; Electric Stimulation; Genetic Programming; Goals; Hippocampus (Brain); Hypothalamic structure; Lead; Learning; Memory; Mission; Nervous System Physiology; Nervous system structure; Neurons; Neuropeptide Receptor; Neurotransmitters; Pattern; Perforant Pathway; Play; Population; Rattus; Research; Role; Site; Spinal Cord; Stimulus; Stress; Synapses; Synaptic Transmission; Testing; Time; United States National Institutes of Health; Work; acute stress; adult neurogenesis; conditioned fear; dentate gyrus; environmental enrichment for laboratory animals; granule cell; mood regulation; nervous system disorder; neural circuit; neurogenesis; neuronal patterning; operation; postsynaptic; presynaptic; public health relevance; receptor; receptor expression; research study; resilience

DESCRIPTION (provided by applicant): The function of the nervous system depends on the appropriate specification of neurotransmitters and their receptors that enable the function of neural circuits. We have discovered that circuit activity plays a key role in transmitter specification (Dulcis and Spitzer, 2008; Dulcis et al., 2013) and that changes in transmitter expression are matched by corresponding changes in postsynaptic receptors (Borodinsky & Spitzer, 2007; Dulcis & Spitzer, 2008; Dulcis et al., 2013), causing changes in behaviors. We now propose to determine whether neurotransmitter switching can be induced by patterns of neuronal activity that induce LTP in the adult rat hippocampus, and whether this is accompanied by changes receptor population. We will also determine whether environmental enrichment and fear conditioning that engage the hippocampus induce neurotransmitter switching. We will test the role of newly expressed transmitters in adult neurogenesis and in the development of resilience to acute and chronic stress. The immediate goal of this research is to test the hypothesis that activation of neural circuits in the hippocampus leads to transmitter respecification in neurons in these circuits, with corresponding changes in adult neurogenesis and/or stress behavior. A long-term goal is to understand how neural network activation can be used to induce neurotransmitter plasticity in the adult brain and ultimately to advance the mission of the NIH to treat neurological disorders.

描述（由申请人提供）：神经系统的功能取决于神经递质及其受体的适当规范，从而使神经回路的功能。我们已经发现，电路活动在发射机规范中起关键作用（Dulcis和Spitzer，2008； Dulcis等，2013），并且通过突触后受体的相应变化，发射机表达的变化匹配（Borodinsky＆Spitzer，2007; Dulcis＆Spitzer＆Spitzer＆Spitzer，2008; Dulcis等人，2013年，2013年，CA）。现在，我们建议确定神经递质切换是否可以通过诱导成年大鼠海马的LTP的神经元活性的模式诱导，以及是否伴随着受体种群的变化。我们还将确定与海马诱导神经递质转换的环境富集和恐惧条件。我们将测试新表达的发射器在成人神经发生以及对急性和慢性应激的韧性发展中的作用。这项研究的直接目的是检验以下假设：海马中神经回路的激活导致这些电路中神经元的发射器分解，并且成人神经发生和/或压力行为的相应变化。一个长期的目标是了解如何使用神经网络激活来诱导成人大脑中的神经递质可塑性，并最终促进NIH的使命治疗神经系统疾病。