Decoding place cell firing-induced synaptic plasticity and cognitive mapping

描述在啮齿动物海马中，CA 3和CA 1锥体细胞之间的突触共有两个关键特性：1）它们的突触强度可通过NMDA受体依赖性长时程增强（LTP）和抑制（LTD）改变; 2）许多CA 3和CA 1锥体细胞的活动是位置特异性的，因为这种“位置细胞”只有当啮齿动物的头部处于被称为“射击场”的特定环境区域时，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 关于环境的信息可以被编码在锥体细胞突触的强度中。例如，基于尖峰定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年）。另一个例子是空间映射的图论，其假定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激发，而连接具有分离场的细胞对的突触应该保持较弱，因为两个细胞将仅在不同时间激发（Muller等人，1996年）。 Isaac和Col.（2009）最近的一份报告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，表明距离编码在单个突触的强度中。在他们的研究中，Isaac和Col.使用了一种“双重刺激”方法，其中一个位置细胞的尖峰活动被用来刺激突触前Shaffer collatera输入到海马切片中的CA 1锥体细胞。在同一时间，第二个，同时记录的位置细胞的活动被用来引起放电的膜片钳突触后CA 1细胞。 尽管有这些进展，仍然不清楚是什么精确的突触编码引起了位置细胞突触的可塑性变化。我们将利用Isaac和Col.（2009）方法来确定1）什么样的突触编码控制受到位置细胞放电刺激的可塑性突触的增强或减弱的幅度，以及2）这种突触编码如何与导航行为相关。 这个项目的意义是双重的。一方面，它是对可塑性突触如何被特定位置的放电（海马体中的初级细胞产生的最强大的信号）改变的经验性探索。另一方面，它将提供一阶测试的理论模型，提出突触可塑性机制的认知映射。

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.