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，在包括小脑在内的一些回路中，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发射有规律的动作电位。在这些神经元中，突触兴奋或抑制不是诱导或阻止动作电位，而是调节内在的放电模式。目前的建议是由什么构成信号和什么构成噪声的问题，在一个系统的自发活动的元素。我们的目标是探索“有效”突触信号背后的机制。即那些显著改变突触后放电的细胞——最终通过可塑性或病理生理学来测试调节或破坏突触信号的后果。

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.