Excitatory synapses in the deep cerebellar nuclei

描述（由申请人提供）：虽然已经清楚地证明小脑参与运动和联想学习，但仍不清楚这种学习在小脑内的何处以及如何发生。许多研究集中在浦肯野细胞的突触生理学和电生理特性上，但很少有研究探讨小脑深部核（DCN）神经元在小脑回路中的作用。对眼睑调节的行为研究表明，至少有一部分小脑学习发生或储存在小脑皮层之外，很可能在DCN中。然而，人们对DCN中兴奋性突触的特性知之甚少，也没有直接证据表明该部位的突触可塑性。这项工作将通过对这些突触的基本特性进行比以前更详细的研究，为DCN中兴奋性突触的功能提供见解。我们将首先研究EPSCs的动力学、药理学敏感性和电压依赖性，以及EPSCs在高频刺激下的短期可塑性。这些信息将有助于理解信息是如何在DCN的兴奋性突触中传递和处理的。此外，我们将研究DCN的兴奋性突触是否存在长期可塑性，如果存在，epsc增强或抑制的条件和机制。这些数据将有助于我们了解信息是如何被小脑，尤其是DCN处理和存储的。

DESCRIPTION (provided by applicant): While it has been clearly demonstrated that the cerebellum is involved in motor and associative learning, it is remains unclear where and how this learning takes place within the cerebellum. Many studies have focused on the synaptic physiology and electrophysiological properties of Purkinje cells, but very few studies have investigated the role of deep cerebellar nuclear (DCN) neurons in the cerebellar circuit. Behavioral studies of eyelid conditioning have suggested that at least a portion of cerebellar learning takes place or is stored outside the cerebellar cortex, likely in the DCN. However, little is known about the properties of excitatory synapses in the DCN and there has been no direct evidence of synaptic plasticity at this site. This work will provide insight on the function of excitatory synapses in the DCN by making a more detailed study of the basic properties of these synapses than has been done previously. We will begin by investigating the kinetics, pharmacological sensitivity, and voltage dependence of EPSCs, as well as the short-term plasticity of EPSCs during trains of high frequency stimulation. This information will help in understanding how information is transmitted and processed at excitatory synapses in the DCN. In addition, we will investigate whether long-term plasticity is possible at excitatory synapses in the DCN, and if so, the conditions and mechanisms that produce potentiation or depression of EPSCs. These data will provide insight on how information is processed and stored by the cerebellum and in the DCN in particular.