What role do different interneurons in medial prefrontal cortex play in associative recognition memory?

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Associative recognition memory is the process that enables us to form normal, every-day memories. This allows us to remember where we parked the car, where we left our keys, or our phone. This type of memory is essential for us to be able to live our normal lives and underlies some of the first noticeable deficits that occur when cognitive decline or Alzheimer's disease begins to set in. Defining the brain processes which give rise to associative memory is important for understanding how the brain operates under normal conditions but is also important in beginning to understand the mechanisms that start to break down in old age or in Alzheimer's disease. Rodents such as rats and mice also use associative recognition memory in their normal lives, and we have shown that a number of different brain regions including the prefrontal cortex, hippocampus, and regions of the thalamus work together during associative recognition memory. These different regions work together with the prefrontal cortex to control the initial learning and then the remembering of the original memory. However, there are still many things that we don't know about how these brain regions operate. One of the questions we will answer is: how do inhibitory cells in the prefrontal cortex control the function of this brain region during associative memory? We propose that the hippocampus and the nuclei of the thalamus control different types of inhibitory cells in the prefrontal cortex and that the separate activation of the different inhibitory cells by these different brain regions separately brings about the initial encoding and then the retrieval of the memory. We will test these ideas in mice by selectively targeting and silencing the major types of interneurons in prefrontal cortex during different phases of memory. We will use advanced anatomical markers and light microscopy methods to detect whether the hippocampus and the thalamic connections to prefrontal cortex terminate on the different inhibitory cell types. Finally, we will examine how these different connections control activity of the different inhibitory cells and therefore control the function of the prefrontal cortex. The project is timely because we have only recently identified the different regions that work together to bring about the different phases of associative recognition memory and it is now possible to identify and selectively target different inhibitory cells while a mouse is performing a learning task. Furthermore, the anatomical methods have recently been developed that now allow us to identify which brain regions connect with which inhibitory cells and finally we can record from these cells to measure how their activity is controlled by the different brain regions that control associative memory. Overall, this work will provide a detailed mechanistic insight into how brain regions work collectively to bring about associative recognition memory.