Causal assessment of bilateral CA3-CA1 communication in hippocampal content representation

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"You see at this moment, everything looks clear to me. But what happened just before? That's what worries me. It's like waking from a dream; I just don't remember." The quote above is from Henry Molaison (H.M.), a patient who had part of his brain surgically removed to cure his epilepsy. H.M., and others like him, taught us that a region of the brain called the hippocampus, and surrounding regions, are crucial for the formation of memories of events and places. In order to understand how the hippocampus and surrounding regions process memories, researchers have turned to animals, particularly rodents. Nerve cells in both the human and rodent hippocampus behave as 'place cells'; that is nerve cells that are preferentially active when the subject is at a particular location. These cells, acting together as a population, might provide the brain with a representation of the surrounding environment used to guide behaviour in space. Hippocampal place cells can also change their activity in response to particular items, odours or sounds experienced at a particular location. These changes may allow the brain to associate discrete locations with a particular piece of information, such as a reward or punishment.The aim of our project is to understand how place cells can acquire information about where a reward is. We will record from the hippocampus in both hemispheres while mice learn to locate reward in different enclosures. Furthermore, we will interfere with learning by temporarily silencing communication between two parts of the hippocampus circuit during learning. This will allow us to determine exactly where within the hippocampus learning-related changes happen.In the final part of the project, we will look at the role of sleep in stabilizing memories. Certain neuronal activity patterns observed during active waking behaviour are reactivated during sleep, possibly for the purpose of stabilizing related memories. We will test this hypothesis by interfering with the communication between hippocampal neurons during sleep and testing the effect of this interference on memory stabilization.Our work should further our understanding of how the hippocampus binds information together to form memories, and how these memories are stabilized during sleep. This will in turn aid efforts to enhance learning and memory in both healthy individuals and those with memory related disorders. In particular, sleep malfunctions have been linked to memory impairments and sleep related interventions seem to help. Understanding exactly how sleep promotes memory stabilization will allow us to refine and optimize sleep-related interventions. Moreover, this work should reveal strategies used by brain circuits to optimize learning, which could inform efforts to mimic what the brain does to achieve efficient machine learning.