Synaptic integration and propagation in CA1 dendrites

树突构成中枢神经系统中大多数神经元的输入结构。 这些精心分支的结构接收数以万计的突触输入，产生突触电位神经元膜电位的瞬时变化，由树突传递到轴突。 为了响应这种突触整合，轴突在适当的时候以动作电位的形式产生输出。 这种树突加工的复杂性由许多因素决定，包括树突的结构、突触和神经递质门控离子通道的性质和分布，以及电压门控离子通道的性质和分布。 树突结构和功能的缺陷与癫痫、帕金森病和精神分裂症等神经疾病有关。 此外，许多被认为是学习基础的突触重构（突触可塑性）发生在树突中，因此可能受到以学习和记忆缺陷为特征的疾病（例如阿尔茨海默病和唐氏综合征）中存在的树突异常的影响。最近的几项研究表明，树突含有电压门控离子通道，其积极地塑造神经元对突触输入的响应，为神经元提供在转换输入和输出的过程中执行复杂计算的潜力。 我们和其他人已经发现，这些通道介导几种不同形式的树突兴奋性。 该提议探讨了与树突兴奋性在突触整合和可塑性中的作用相关的三个假设：1）树突兴奋性参与突触可塑性的诱导，2）树突兴奋性本身可以通过活动进行修饰，3）树突兴奋性可以通过神经递质系统进行调节。 我们将应用树突状细胞膜片钳记录和钙离子成像技术对海马脑片上的CA 1锥体神经元进行研究。 除了探索树突兴奋性在突触可塑性中的作用之外，这些研究还探索了树突兴奋性的变化可以改变神经元的输入-输出功能的想法，这可能构成细胞水平上的另一种学习形式。 因此，这些研究验证了树突兴奋性在功能上很重要的假设，无论是在树突局部（触发突触强度的变化），还是在神经元的输出，在索马和轴突中，增加了轴突电位产生的概率。

Dendrites constitute the input structure of most neurons in the central nervous system. These elaborately branching structures receive tens of thousands of synaptic inputs, which produce synaptic potentials-transient changes in the membrane potential of the neuron that are processed by the dendrites passed on to the axon. In response to this synaptic integration, the axon produces an output in the form of an action potential, when appropriate. The complexity of this dendrite processing is determined by many factors, including the structure of the dendrites, the properties and distribution of synapses and neurotransmitter-gated ion channels, as well as the properties and distribution of voltage-gated ion channels. Defects in dendritic structure and function have been linked to neural diseases such as epilepsy, Parkinson's disease, and schizophrenia. Furthermore, much of the synaptic restructuring (synaptic plasticity) believed to underlie learning takes place in dendrites, and therefore may be affected by the dendritic abnormalities present in disorders characterized by deficiencies in learning and memory, such as Alzheimer's disease and Down's syndrome. Several recent studies have demonstrated that dendrites contain voltage- gated ion channels, which actively shape the response of a neuron to synaptic input, providing neurons with the potential to perform complex computations in the process of converting inputs and outputs. We and others have found that these channels mediate several different forms of dendritic excitability. This proposal explores three hypotheses related to the role of dendritic excitability in synaptic integration and plasticity: 1) That dendritic excitability is involved in the induction of synaptic plasticity, 2) That dendritic excitability itself can be modified by activity, and 3) That dendritic excitability can be modulated by neurotransmitter systems. We will test these hypotheses by applying dendritic patch-clamp recording and Ca 2+ -imaging methods to CA1 pyramid neurons in the hippocampal slice preparation. In addition to exploring the role of dendritic excitability in the synaptic plasticity underlying, these studies explore the idea that changes in dendritic excitability can modify the input -output function of a neuron, which may constitute another form of learning at the cellular level. Thus, these studies test the hypothesis that dendritic excitability is functionally important, both locally in the dendrites (triggering changes in synaptic strength) and at the output of the neuron, in the soma and axon, increasing the probability that an axonal potential will be produced.