Targeting the ventral hippocampus for a better model of temporal lobe epilepsy

项目摘要/摘要 这项提案的主要目标是为癫痫研究提供一个急需的工具--a 具有目前广泛使用的海人藻酸盐模型优点的颞叶癫痫模型 而且还表现出自发的、公开的行为发作，频率足够高，足以让科学 调查。为了做到这一点，我们建议对当前的诱导协议进行简单的更改，并可能 一个巨大的影响。具体地说，尽管已知背部和背部在连通性和功能特性上的差异 和腹侧海马区，并观察到人类患者的前海马区 (对应于啮齿类动物的腹侧海马体)最有可能表现为海马体硬化，在其 目前的形式是，海马内海人酸模型的目标是背侧(而不是腹侧)海马体。我们 假设更好地使模型与人类状况保持一致，方法是将最初的侮辱位置移到 腹侧海马区，还会导致明显更高的行为发作频率。 这是至关重要的，因为它将为实地提供一个急需的工具，使更多的调查成为可能。 具有足够统计能力和可行性的严重癫痫发作和确定新的治疗方法 数据采集的时间范围。

PROJECT SUMMARY/ABSTRACT The primary objective of this proposal is to produce a much needed tool for epilepsy research – a model of temporal lobe epilepsy with the strengths of the currently widely used intrahippocampal kainate model but also displaying spontaneous, overtly behavioral seizures, at a high enough frequency to allow scientific investigation. To do this, we propose a simple change to the current induction protocol, with the possibility for a huge impact. Specifically, despite known differences in connectivity and functional properties between dorsal and ventral hippocampus, and the observation that in human patients the anterior hippocampus (corresponding to the ventral hippocampus in rodents) is most likely to show hippocampal sclerosis, in its current form, the intrahippocampal kainate model targets the dorsal (rather than ventral) hippocampus. We hypothesize that better aligning the model to the human condition, by moving the site of initial insult to the ventral hippocampus, will additionally result in a substantially higher frequency of overtly behavioral seizures. This is critically important, as it would provide the field with a much needed tool, allowing investigation of more severe seizures and identification of novel treatment approaches with sufficient statistical power and feasible time frames for data acquisition.