Integration of Sensory and Temporal Information in CA3

摘要 记忆是时间性的。当我们回忆一个事件时，我们也会回忆它发生的相对时间 经验丰富。大脑是如何计算和存储记忆的时间表征的？的 海马体对记忆的时间组织很重要。海马CA1或CA3病变导致 按时间分隔的连续事件的编码受损。海马体连接着大脑中 在延迟期间通过神经集合顺序地触发的顺序事件。这些“时间细胞” 在所述延迟期间顺序地编码连续时刻。我们实验室和其他小组最近的工作 证实并进一步证实了这些发现。他们发现海马体的CA1区 包含的神经元显示刺激特定的顺序放电模式在延迟期间的工作 记忆任务CA1在很大程度上缺乏周期性连接，因此它不太可能产生这些连续的放电 自己的模式。CA3是通过Schaffer侧枝直接连接到CA1的上游区域。 CA3具有广泛的重复连接，并且是产生这些刺激特异性的可能候选者。 连续的射击模式CA3中的循环连接非常适合存储和处理 临时信息，因为它们允许快速关联。CA3还接收来自横向 内嗅皮层，它处理非空间感觉信息，并接收来自大脑的直接连接。 嗅球到目前为止，它是未知的感觉和时间信息是如何整合的。鉴于 CA3的独特属性，我们认为CA3是感觉和时间信息整合的地方， 则该代码被传递到CA 1。为了验证这一假设，我们将使用尖端的慢性体内双光子 钙成像以监测工作记忆任务期间的CA3神经元群体。此外，我们将使用 同时进行体内双光子成像和光遗传学以调节CA3内的靶向亚群 在刺激呈现期间或在工作记忆任务的延迟期间是活跃的。这将允许 我们来研究感官和时间信息之间的因果关系。这些实验将奠定 理解记忆元素如何在CA3中统一和编码的基础。

ABSTRACT Memories are temporally organized. When we recall an event, we also recall the relative timing it was experienced. How does the brain compute and store this temporal representation of memory? The hippocampus is important to the temporal organization of memories. Hippocampal CA1 or CA3 lesions cause impaired coding of sequential events separated by time. The hippocampus bridges stimuli-free gaps between sequential events through neural ensembles that fire sequentially during the delay. These “time cells” fire sequentially encoding successive moments during the delay. Recent work in our laboratory and other groups have confirmed and furthered these findings. They have found that the CA1 region of the hippocampus contains neurons that display stimulus-specific sequential firing patterns during the delay period of a working memory task. CA1 largely lacks recurrent connectivity, so it is unlikely that it generates these sequential firing patterns on its own. CA3 is an upstream region with direct connections through the Schaffer collaterals to CA1. CA3 has extensive recurrent connections and is a likely candidate that generates these stimulus-specific sequential firing patterns. The recurrent connections in CA3 are well-suited for storing and working with temporary information because they allow for rapid associations. CA3 also receives input from the lateral entorhinal cortex, which processes nonspatial sensory information and receives direct connects from the olfactory bulb. To date, it is unknown where and how sensory and temporal information is integrated. Given the unique attributes of CA3, we propose that CA3 is where sensory and temporal information is integrated and then this code is passed onto CA1. To test this hypothesis, we will use cutting-edge chronic in vivo two-photon calcium imaging to monitor CA3 neuronal populations during a working memory task. Additionally, we will use simultaneous in vivo two-photon imaging and optogenetics to modulate targeted sub-populations within CA3 that are active during stimulus presentation or during the delay period of a working memory task. This will allow us to examine the causal relationships between sensory and temporal information. These experiments will lay the groundwork for understanding how elements of a memory are unified and coded within CA3.