Decoding place cell firing-induced synaptic plasticity and cognitive mapping

描述(申请人提供)：在啮齿动物的海马区，CA3和CA1锥体细胞之间的突触有两个关键特性：1)它们的突触强度可被NMDA受体依赖的长时程增强(LTP)和抑制(LTD)所改变；2)许多CA3和CA1锥体细胞的活动是位置特定的，因为只有当啮齿类动物的头部处于一个称为“激发野”的特定环境区域时，这种“定位细胞”才能快速放电。突触可塑性和位置特异性放电的结合表明，重要的空间 关于环境的信息可能编码在锥体细胞突触的强度中。例如，基于峰时依赖可塑性规则的空间映射理论表明，方向向量可以在突触中编码(Blum和Abbott，1996；Bush等人，2010)。另一个例子是空间映射的图论，该理论假设连接具有重合或重叠场的细胞对的突触应该加强，因为两个细胞将一起发射，而连接具有分离的场的细胞对的突触应该保持弱，因为两个细胞只在不同的时间发射(Muller等人，1996)。艾萨克和科尔最近的一份报告。(2009)提供了令人兴奋的证据，加强了位置细胞尖峰活动和突触功能之间的联系，表明距离是由单个突触的强度编码的。在他们的研究中，艾萨克和科尔。使用“双重刺激”的方法，其中一个部位细胞的放电活动被用来刺激突触前Shaffer侧支输入到海马片上的CA1锥体细胞。同时，第二个同时记录的位置细胞的活动被用来唤起膜片钳突触后CA1细胞的放电。尽管取得了这些进展，但仍不清楚是什么精确的突触编码导致了位置细胞突触的可塑性变化。我们将利用艾萨克和科尔。(2009)确定1)什么样的突触编码控制着受定位细胞放电刺激的可塑性突触的加强或减弱的幅度，以及，2)这种突触编码与导航行为的关系。这个项目的意义是双重的。一方面，这是一项关于定位放电如何改变可塑性突触的经验探索，定位放电是海马体中初级细胞产生的最强大的信号。另一方面，它将提供理论模型的一阶测试，这些模型假设突触可塑性机制是认知映射的基础。

DESCRIPTION (provided by applicant): In the rodent hippocampus, synapses between CA3 and CA1 pyramidal cells share two key properties: 1) their synaptic strength is modifiable by NMDA receptor dependent long-term potentiation (LTP) and depression (LTD); 2) the activity of many CA3 and CA1 pyramidal cells is location specific in that such "place cells" discharge rapidly only when a rodent's head is in an environment-specific region called the "firing field". The combination of synaptic plasticity and location-specific firing suggests that important spatial information about the environment may be encoded in the strength of pyramidal cell synapses. For instance, theories of spatial mapping based on spike-timing dependent plasticity rules suggest that directional vectors can be encoded in synapses (Blum and Abbott, 1996; Bush et al., 2010). Another example is the graph theory of spatial mapping, which posits that synapses connecting cell pairs with coincident or overlapping fields should strengthen since the two cells will fire together whereas synapses connecting cell pairs with separated fields should remain weak since the two cells will fire only at different times (Muller et al., 1996). A recent report y Isaac and col. (2009) has provided with exciting evidence that strengthens the link between place cell spiking activity and synaptic function, demonstrating that distance is encoded in the strength of individual synapses. In their studies, Isaac and col. used a "dual stimulation" method where the spiking activity of one place cell is used to stimulate the presynaptic Shaffer collatera input to a CA1 pyramidal cell in a hippocampal slice. At the same time, the activity of a second, simultaneously recorded place cell is used to evoke discharge of the patch-clamped postsynaptic CA1 cell. In spite of these advances, there still is unclear what precise synaptic encoding give rise to plastic changes in synapses of place cells. We will utilize the Isaac and col. (2009) method to identify 1) what kind of synaptic encoding govern the magnitude of strengthening or weakening of plastic synapses subjected to place cell firing stimulation, and, 2) how this synaptic encoding relates to navigational behavior. The significance of this project is two-fold. On one hand it is an empirical exploration of how plastic synapses are modified by location-specific firing, the most powerful signal generated by primary cells in the hippocampus. On the other hand, it will provide first order tests of theoretical models that pose synaptic plasticity mechanisms underlie cognitive mapping.