Synaptic integration and propagation in CA1 dendrites

树突构成了中枢神经系统中大多数神经元的输入结构。这些精细的分支结构接受数以万计的突触输入，这些突触输入产生突触电位——神经元膜电位的短暂变化，由传递给轴突的树突处理。作为对这种突触整合的反应，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是由许多因素决定的，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组（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（如阿尔茨海默病和唐氏综合症）中树突异常的影响。最近的一些研究表明，树突包含电压门控离子通道，这些通道积极地塑造神经元对突触输入的反应，为神经元提供在转换输入和输出过程中执行复杂计算的潜力。我们和其他人已经发现，这些通道介导了几种不同形式的树突兴奋性。本文探讨了树突兴奋性在突触整合和可塑性中的作用的三种假说：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被活动修饰；3)树突兴奋性可以被神经递质系统调节。我们将通过树突膜片钳记录和ca2 +成像方法对海马切片制备中的CA1锥体神经元进行验证。除了探索树突兴奋性在突触可塑性基础中的作用外，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，这可能构成细胞水平上另一种形式的学习。因此，这些研究验证了树突兴奋性在功能上很重要的假设，既在局部树突（触发突触强度的变化），也在神经元的输出，在体细胞和轴突，增加了轴突电位产生的可能性。

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.