Cellular and molecular mechanisms that modulate synaptic function and plasticity

关于特定的分子变化如何改变突触生理学， 特定的行为偏好和记忆。关于细胞生物学的知识 突触在记忆激活过程中的改变对于我们理解 神经系统的组成部分聚集在一起产生功能输出，行为。的 本提案的总体目标是确定C.热感觉神经元之间的elegans突触 AFD和它唯一的突触后伙伴（AIY）被经验修改，以表达习得的温度 偏好我们的中心假设是，温度偏好记忆在AFD中是通过 突触前可塑性，这反过来又通过蛋白激酶C ε/eta（nPKCε）依赖性 机制等我们的假设是基于我们的初步研究和已发表的发现，这些发现表明， 改变单个神经元（AFD）中的nPKCε活性足以改变神经元的温度偏好。 不管以前的经验。我们发现nPKCε定位于突触前位点附近， AFD感觉信息传递到其突触后伙伴（AIY）。拟议目标的理由 我们可以使用C语言的紧凑神经回路。elegans来剖析保守的分子，比如nPKCε， 调节突触前可塑性以调节经验依赖性适应行为。我们建议使用 遗传学、细胞生物学、药理学、行为学和钙成像方法来实现我们的三个目标。 具体目的：（1）确定nPKCε在调节AFD：AIY化学突触中的作用;（2）确定nPKCε在AFD：AIY化学突触中的作用。 调节nPKCε激活的分子机制;（3）确定突触前可塑性机制 由nPKCε调节。在成功完成拟议目标后，我们预计贡献将是 详细的分子和细胞生物学的理解，如何温度偏好记忆是启动， 通过保守的nPKCε通路介导的突触前可塑性的调节而在体内发挥作用。技术 这一提议中的概念创新通过提供进入记忆中心的途径开辟了新的视野 在活体动物和细胞生物学分辨率的驱动。我们预计，由于分子 保护所研究的途径，基于这些创新， 将导致具有广泛生物学意义的转座课程。

A gap in knowledge remains regarding how specific molecular changes that alter synaptic physiology actuate particular behavioral preferences and memories in living animals. Knowledge on how the cell biology of synapses is altered in the actuation of memories is of critical importance in our aspiration to understand how the building blocks of the nervous system come together to produce its functional output, behaviors. The overall objective of this proposal is to determine how C. elegans synapses between the thermosensory neuron AFD and its only postsynaptic partner (AIY) are modified by experiences to express a learned temperature preference. Our central hypothesis is that temperature preference memory is actuated in AFD through presynaptic plasticity, which is in turn regulated through Protein Kinase C epsilon/eta (nPKCε)-dependent mechanisms. Our hypothesis is based on our preliminary studies and published findings that indicate that altering nPKCε activity in a single neuron (AFD) is sufficient to change the temperature preference of the organism regardless of previous experience. We found that nPKCε localizes near presynaptic sites and alters transmission of AFD sensory information to its postsynaptic partner (AIY). The rationale of the proposed aims is that we can use the compact neural circuitry of C. elegans to dissect how conserved molecules, like nPKCε, regulate presynaptic plasticity to modulate experience-dependent adaptive behaviors. We propose to use genetic, cell biological, pharmacological, behavioral and calcium imaging approaches to achieve our three specific aims: (1) Identify the role of nPKCε in modulating the AFD:AIY chemical synapse; (2) Identify the molecular mechanisms that regulate nPKCε activation; and (3) Identify the presynaptic plasticity mechanism regulated by nPKCε. Upon successful completion of the proposed aims we expect the contribution to be a detailed molecular and cell biological understanding of how the temperature preference memory is actuated in vivo through the regulation of presynaptic plasticity mediated by the conserved nPKCε pathways. The technical and conceptual innovations in this proposal open up new horizons by providing access to the hubs of memory actuation in living animals and with cell biological resolution. We anticipate, because of the molecular conservation of the examined pathways, that advancements in our understanding based on these innovations will result in transposable lessons of broad biological significance.