The Role of Inhibitory Mechanisms on Governing the Hippocampal Temporal Code

描述（由申请人提供）：海马体在学习和记忆中具有明确的作用（Scoville & Milner, 1957; Squire, 1992），海马体损伤是多种神经系统疾病（如阿尔茨海默病、癫痫和中风）引起的记忆障碍的主要原因。海马体的体内电生理研究揭示了一些显著的活动模式。具体来说，啮齿动物和人类的海马细胞都以空间选择性的方式放电（O'Keefe and Dostrovsky, 1971； O'Keefe and Recce, 1993; Ekstrom et al., 2003, 2005）。发射速率（速率码）和脉冲定时（时间码）都包含有关空间环境的信息。然而，引起海马速率和时间代码的细胞和电路机制仍然没有得到很好的理解，并且对抑制如何塑造这些海马活动模式知之甚少。我将结合体内和体外实验与计算模型来研究控制海马颞叶密码的抑制机制。通过这样的理解，我们可以精确地指出回路的哪些特性对海马体功能至关重要。这可以为我们指明治疗由海马损伤引起的临床疾病的新目标。相关性：人类的海马体对学习和记忆很重要，但它很容易受损：中风、痴呆（包括阿尔茨海默病）、癫痫和缺氧都可能导致海马体受损，从而导致学习和记忆困难。通过了解海马体的神经密码，我们可以精确地确定哪些细胞和回路对学习和记忆至关重要。这可以为我们指明治疗由海马损伤引起的问题的新目标。

DESCRIPTION (provided by applicant): The hippocampus has a well established role in learning and memory (Scoville & Milner, 1957; Squire, 1992), and hippocampal damage is primarily responsible for the memory impairments resulting from a variety of neurological conditions such as Alzheimer's disease, epilepsy and stroke. In vivo electrophysiological studies of the hippocampus have revealed some salient activity patterns. Specifically, hippocampal cells in both rodents and humans fire in a spatially selective manner (O'Keefe and Dostrovsky, 1971; O'Keefe and Recce, 1993; Ekstrom et al., 2003, 2005). Both the firing-rate (rate code) and spike-timing (temporal code) contain information about the spatial environment. However, the cellular and circuit mechanisms that give rise to the hippocampal rate and temporal codes are still not well understood, and little is known about how inhibition shapes these hippocampal activity patterns. I will combine in vivo and in vitro experiments with computational modeling to investigate the inhibitory mechanisms governing the hippocampal temporal code. Using such an understanding, we can precisely pinpoint what properties of the circuit are crucial for hippocampal function. This can point us towards novel targets for treating clinical ailments resulting from hippocampal damage. Relevance: The human hippocampus is important for learning and memory but it is prone to damage: strokes, dementias (including Alzheimer's disease), epilepsies and hypoxia can all lead to hippocampal damage, and subsequent learning and memory difficulties. By understanding the neural code of the hippocampus we can precisely pinpoint which of its cells and circuits are crucial for learning and memory. This can point us towards novel targets for treating problems resulting from hippocampal damage.