Calcium Waves in Pyramidal Neurons

海马锥体神经元突触后[Ca ~（2+）]i的变化在海马神经元突触损伤中起重要作用。 在诱导各种形式的突触可塑性，基因表达， 和膜电导的调节。所有这些机制都会影响 这些神经元在参与学习和记忆的回路中的行为。因此 对这些过程的详细了解对于理解大脑功能是重要的。 在锥体神经元中有三个明确的Ca 2+来源，它们可以被激活， 海马中的突触机制：通过NMDA受体的Ca 2+内流， 通过电压依赖性Ca 2+通道，和Ca 2+从内部存储释放。我们 将研究钙离子释放的性质和功能，从商店介导的 来自Sprague海马CA 1区的切片中锥体细胞中的IP 3 道利老鼠。第一组实验将检查新发现的 这些神经元的主要树突中的自发基本事件（“抽吸”）。这些 局部事件可以通过膜电位和mGluR介导的突触 传输，并且自身可以具有重要的信号功能。第二 一组实验将检查这些事件在斜枝晶中的性质， 索马和轴突。先前的实验确定了Ca 2+释放波， 可能是由这些事件造成的，但在这些地区却没有发现。我们将努力 了解波浪的有限空间分布和更广泛的分布 基本事件。这些事件的地点和时间进程将被审查 高速成像和双光子显微镜。突触刺激 传输将补充细胞外谷氨酸的局灶性释放， 卡巴胆碱和细胞内IP 3和Ca 2+，以实现信号传导的精确定位 在厚或薄的树枝状区域中的事件。我们将探讨钙离子释放的功能 从商店在几个重要的生理过程中，特别强调 在不同的树突状区域释放的Ca 2+的不同后果。一组 实验将研究Ca 2+释放在诱导细胞可塑性中的作用， 兴奋性第二组实验将研究Ca 2+波在 抑制内源性神经递质介导的锥体神经元突触抑制 大麻素

Postsynaptic [Ca2+]i changes in pyramidal neurons in the hippocampus play an important role in the induction of various forms of synaptic plasticity, gene expression, and modulation of membrane conductances. All of these mechanisms can affect the behavior of these neurons in circuits involved in learning and memory. Therefore, a detailed understanding of these processes is important for understanding brain function. There are three clear sources of Ca2+ in pyramidal neurons that can be activated by synaptic mechanisms in the hippocampus: Ca2+ entry through NMDA receptors, entry through voltage-dependent Ca2+ channels, and Ca2+ release from internal stores. We will investigate the properties and functions of Ca2+ released from stores mediated by IP3 in pyramidal cells in slices from the CA1 region of the hippocampus in Sprague Dawley rats. The first set of experiments will examine the properties of newly discovered spontaneous elementary events ("puffs") in the main dendrites of these neurons. These local events can be modulated by membrane potential and mGluR mediated synaptic transmission and could have important signaling functions by themselves. The second set of experiments will examine the properties of these events in the oblique dendrites, soma, and axon. Previous experiments established that Ca2+ release waves, which are probably built from these events, are not found in these regions. We will try to understand the restricted spatial distribution of waves and more widespread distribution of elementary events. The location and time course of these events will be examined with high speed imaging and 2-photon microscopy. Stimulation with synaptic transmission will be supplemented with focal uncaging of extracellular glutamate and carbachol and intracellular IP3 and Ca2+ to achieve precise localization of signaling events in thick or thin dendritic regions. We will investigate the function of Ca2+ released from stores in several important physiological processes, with particular emphasis on the different consequences of Ca2+ released in different dendritic regions. One set of experiments will examine the role of Ca2+ release in the induction of plasticity of cell excitability. A second set of experiments will examine the role of the Ca2+ waves in suppressing synaptic inhibition onto pyramidal neurons mediated by endogenous cannabinoids.