CA3RECURRENTPLASTIC · In vivo dynamics and plasticity of networks within CA3 of the hippocampus: effects of optogenetic stimulation and natural learning.

In vivo dynamics and plasticity of networks within CA3 of the hippocampus: effects of optogenetic stimulation and natural learning.

Our work focuses on the neural mechanisms responsible for the formation, consolidation, and recall of memories. The prevalence of memory disorders, such as Alzheimer’s dementia and post-traumatic stress disorder, necessitate efforts to understand the neural mechanisms underlying memory. There are many types of memories, and each is formed by a specific region of the brain. Episodic memories are those of autobiographical events, and they are processed by a deep brain structure called the hippocampus. These memories include information about what, where, and when an event happened. Much of what we know about the role of the hippocampus in episodic memories comes from patient H.M., whose hippocampi were surgically removed to alleviate severe epilepsy. After the procedure, he could not form any new memories of experienced events. Interestingly, many of the hippocampal neurons that are active during the formation of a memory are also active during its consolidation and recall. How, then, can very different processes be mediated by the same neurons in the same network? We have several clues to how this may happen. First, different mnemonic processes occur at different times; during periods of activity, the hippocampus forms new memories and recalls older ones; and during periods of rest, it consolidates memories into long-term storage. Second, during activity and rest, the hippocampus shows different patterns in the local field potential (LFP), reflecting broad changes in the coordinated activity of many neurons. Therefore, we know that global changes take place to alter the function of the network between different brain states. Our primary aim is to classify the changes that occur within individual cells in the hippocampus, and infer how this affects their ability to integrate inputs and thus participate in ongoing network computations. Our secondary aim is to dissect the potential neural correlates of memories themselves. Recent research shows that the group of cells participating in the formation of a memory form a neural ensemble. Separate lines of research have shown that cells can change the strength of their connections through synaptic plasticity, and that memory formation depends on this ability. Thus, a leading hypothesis is that ensembles of neurons alter their connections to one another, and this is the physical basis of memory. However, much of what we know about synaptic plasticity comes from in vitro experiments, which are very useful, but often miss some aspects of the physiological condition in vivo. Thus, we have striven to bridge the gap between different lines of research by inducing synaptic plasticity in vivo. Specifically, we aim to show whether specific types of synaptic plasticity studied in vitro can occur in vivo. These aims will bring us closer to understanding the relationships between the dynamics of single cells and networks.

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