Neurotransmitter Switching and Its Function in Hippocampal Plasticity

说明(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格，使神经回路发挥功能。我们发现，电路活动在递质规范中发挥着关键作用(Dulcis和Spitzer，2008；Dulcis等人，2013)，并且递质表达的变化与突触后受体的相应变化相匹配(Borodinsky&Spitzer，2007；Dulcis&Spitzer，2008；Dulcis等人，2013)，从而导致行为变化。我们现在建议确定是否可以通过诱导成年大鼠海马区LTP的神经元活动模式来诱导神经递质转换，以及这是否伴随着受体数量的变化。我们还将确定环境丰富和恐惧条件作用于海马体是否会导致神经递质的切换。我们将测试新表达的递质在成人神经发生和对急性和慢性应激的恢复能力发展中的作用。这项研究的直接目标是检验一种假设，即激活海马体中的神经回路导致这些回路中的神经元递质重新专门化，并在成人神经发生和/或应激行为中发生相应的变化。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，并最终推进NIH治疗神经疾病的使命。

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.