Ionic currents and spiking in cerebellar nuclear neurons

描述（由申请人提供）：许多神经元在突触兴奋之前是沉默的。然而，在一些回路中，包括小脑的回路，越来越清楚的是，单个神经元本质上是活跃的，在没有突触输入的情况下自发地激发规则的动作电位。在这样的神经元中，不是诱导或阻止动作电位，而是突触兴奋或抑制调节内在放电模式。目前的建议是由什么构成的信号和什么构成的噪声在一个系统中的自发活动的元素的问题。我们的目标是探索“有效”突触信号的机制-即那些显着修改突触后放电-并最终测试调制或破坏突触信号的后果，无论是通过可塑性或病理生理学。 拟议的研究重点是浦肯野神经元和小脑核神经元之间的突触传递。将使用来自2-3周龄野生型和共济失调小鼠的组织。实验将在急性分离的小脑核神经元或小脑切片中进行，其中浦肯野神经元的突触接触是完整的。通过刺激浦肯野细胞传入神经诱发的抑制性突触反应的电压钳和电流钳记录、抑制性神经递质受体动力学记录和组织学研究，将用于检查浦肯野-核细胞突触处突触抑制的潜在机制。由此产生的数据将提供有关神经回路中自发活动元件的适应性意义的一般信息，以及有关功能和功能失调的小脑中信息传递的细胞基础的具体信息。

DESCRIPTION (provided by applicant): Many neurons are silent until excited synaptically. In some circuits, including those of the cerebellum, however, it is becoming clear that individual neurons are intrinsically active, firing regular action potentials spontaneously, in the absence of synaptic input. In such neurons, rather than inducing or preventing action potentials, synaptic excitation or inhibition modulates the intrinsic firing pattern. The current proposal is motivated by the question of what constitutes signal and what constitutes noise in a system with spontaneously active elements. The goal is to explore the mechanisms underlying "effective" synaptic signals--i.e. , those that significantly modify postsynaptic firing--and ultimately to test the consequences of modulating or disrupting synaptic signals, either by plasticity or by pathophysiology. The proposed research focuses on synaptic transmission between Purkinje neurons and cerebellar nuclear neurons. Tissue will be used from 2-3 week old wild-type and ataxic mice. Experiments will be performed on cerebellar nuclear neurons either in acute isolation or in cerebellar slices in which synaptic contacts from Purkinje neurons are intact. Voltage-clamp and current-clamp recordings of inhibitory synaptic responses evoked by stimulation of Purkinje cell afferents, recordings of inhibitory neurotransmitter receptor kinetics, and histological studies will be used to examine the mechanisms underlying synaptic depression at the Purkinje-to-nuclear cell synapse. The resulting data will provide general information about the adaptive significance of spontaneously active elements in neural circuits, as well as specific information about cellular basis of information transfer in the functional and dysfunctional cerebellum.