Cellular Information Processing in the Hippocampus

描述（由申请人提供）：有令人信服的证据表明哺乳动物海马体参与学习和记忆以及某些神经和精神疾病。我们的长期目标是了解单个锥体神经元如何整合来自成千上万个突触的输入，从而参与海马体的正常和异常功能。在之前的工作中，我们发现了许多电压门控离子通道（例如Na+， Ca2+和K+）的树突表达，并证明了这些通道如何调节突触整合和突触可塑性的诱导和表达。我们还发现，其中一些树突通道，包括h通道，经历了活动依赖的可塑性，称为内在可塑性，

DESCRIPTION (provided by applicant): There is compelling evidence for the involvement of the mammalian hippocampus in learning and memory as well as certain neurological and psychiatric disorders. Our long-term objective is to understand how single pyramidal neurons integrate input from the tens of thousands of synapses impinging on their dendrites and thereby participate in normal and abnormal functioning of the hippocampus. In previous work we discovered the dendritic expression of a number of voltage-gated ion channels (e.g., Na+, Ca2+, and K+) and demonstrated how these channels regulate both synaptic integration and the induction and expression of synaptic plasticity. We also found that several of these dendritic channels, including h channels, undergo activity-dependent plasticity, called Intrinsic Plasticity, which regulates the excitability of neurons. In animal models for temporal lobe epilepsy (TLE), we found a significant reduction in dendritic K+ and h channels, and recently we showed that a knockdown of the HCN1 subunit for h channels in dorsal hippocampus produces anti-depression and anti-anxiety like behaviors in rats. From the clinical literature there appears to be a strong co-morbidity for depression and anxiety in epilepsy. The findings that a loss of h channels occurs in TLE and a knockdown of h channels produces anti-depressive behaviors, however, appear to be contradictory with this clinical literature. Our preliminary data suggest that this apparent contradiction may be due to a different involvement of the dorsal and ventral hippocampus in these disease models. We propose here to determine 1) the electrophysiological properties of single pyramidal neurons along the entire dorsal-ventral axis of the hippocampus, 2) whether h channels and inward rectifier K+ channels are differentially expressed in these regions, and 3) whether these channels are altered in a region-specific manner in animal models for temporal lobe epilepsy and depression. The experiments will utilize hippocampal brain slices from rats, somatic and dendritic patch-clamp electrophysiology, and immunohistochemistry and western blotting.