Functional architecture of the cortical memory network

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Memories of daily experiences are vital to our day-to-day living. The long-term goal of my research is to uncover how these memories emerge from the coordinated activity of brain cells. During the past ten years, I have used a simple associative memory paradigm in rats, called trace eyeblink conditioning, and identified that the associative memory initially depends on a brain region called the hippocampus, but with time it comes to depend on another brain region called the medial prefrontal cortex (mPFC). With the last five years of NSERC funding, my research team identified that another brain region, the entorhinal cortex (EC) plays an important role for the memory by initially interacting with the hippocampus, but later with the mPFC. In the next five years, we will expand these findings with three parallel studies. First, we will examine how neurons in the EC respond to several variables which consist of an experience in trace eyeblink conditioning. This will identify the most relevant variable for the memory representation in the EC. Second, we will examine a mechanism which allows for a better coordination of EC and mPFC for older memories. Specifically, we will determine whether connections between neurons in the EC and mPFC are strengthened as the associative memory is stabilized. In parallel, we will reversibly cut the connection between the EC and mPFC while the associative memory is stabilized and examine the impact of the manipulation on animals’ ability to later recall the memory. Lastly, we will identify a specific activity pattern of brain cells which is responsible for the formation of memory. Our past studies reported that cells in the mPFC show several patterns of activity while rats form associative memory in trace eyeblink conditioning. But, a question is whether the memory is formed because of these activity patterns. To address this point, we will test whether the associative memory is formed when the cells in the mPFC are stimulated as the same pattern as those observed during normal memory formation. Together, these studies combine state-of-art approaches to provide new insights into how brain cells represent and compute memories. By doing so, the proposed studies will bring us a step closer toward a mechanistic account of our fundamental cognitive ability.