RPG: Characterization of Angiotensin II as a Potential Volume Transmitter in the Central Extended Amygdala

突触传递是在细胞水平上理解神经系统基本运作的关键。没有传递，神经元之间就没有直接的交流。经典观点认为，传递是一种化学信号，被称为传递器，从一个神经元释放出来，然后扩散到其他神经元或目标细胞，在那里它与受体结合，触发一个信号，刺激、抑制或调节细胞活动。最近，使用细胞外液途径的体积传递已被认为是神经元间通信的另一种形式。体积传递不仅包括体液因子通过细胞外液扩散到神经元或神经胶质细胞上的特定受体，还包括沿这些通路的电紧张信号的扩散。神经肽储存在靠近细胞外空间的神经末梢的大而致密的囊泡中，可能是理解体积传递的关键。Zardetto-Smith博士将使用这项研究计划拨款来研究神经肽血管紧张素II在体积传输中的作用。血管紧张素II主要被认为是在细胞外液含量耗竭时调节水的摄入，但它也会诱导寻找和摄入含盐液体。Zardetto-Smith博士设计了一系列实验来检验血管紧张素II是否在体积传递模式下起作用，可能是通过与特定GABAnergic神经元的相互作用，在挑战体液稳态的条件下。这些发现将有助于我们更好地理解在介导神经元间通信中，递质和受体的位置分离所导致的悖论。它还将提供关于钠食欲的神经调节的新信息，鉴于钠在细胞内机制中的重要性，这对我们的生存至关重要。

Zardetto-Smith 9707672 Synaptic transmission is the key to understanding the basic operation of the nervous system at a cellular level. Without transmission, there is no direct communication between neurons. The classical view of transmission is that of a chemical signal, referred to as a transmitter, released from one neuron which then diffuses to other neurons or target cells where it binds to a receptor and triggers a signal which excites, inhibits, or modulates cellular activity. More recently, volume transmission which uses extracellular fluid pathways has been recognized an alternative form of interneuronal communication. Volume transmission includes not only the diffusion of humoral factors through the extracellular fluid to their specific receptors on neurons or glial cells but also the diffusion of electrotonic signals along those pathways. Neuropeptides, which are stored within large dense-cored vesicles in nerve terminals located near extracellular space, may be key to understanding volume transmission. Dr. Zardetto-Smith will use this Research Planning Grant to examine the role that the neuropeptide, angiotensin II, plays in volume transmission. Angiotensin II is primarily known for mediation of the intake of water in response to depletion of the extracellular fluid content but it will also induce seeking out and ingestion of salty fluids. Dr. Zardetto-Smith has designed a series of experiments to examine whether angiotensin II functions in a volume transmitter mode, possibly through interactions with specific GABAnergic neurons, under conditions which challenge body fluid homeostatis. These findings will help us better understand the paradox resulting from the dissociation between the location of transmitters and their receptors in mediating interneuronal communication. It will also provide new information on the neural regulation of sodium appetite which is very important given the significance of sodium in intracellular mechanisms that are essential for our survi val.