Reconsolidation as a mechanism for the homeostatic regulation of synaptic strength

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In the brain and spinal cord, information is passed between nerve cells through connections called synapses that functionally join nerve cells and serve as key points for chemical communication. The flow of information between these cells can be changed by changing how strongly connected two nerve cells are. The ability to change the strength of connections between nerve cells is a fundamental property of the nervous system called plasticity. These plastic changes in synaptic strength are thought to form the building blocks of memory and learning. Importantly, plastic changes between nerve cells are not necessarily permanent, and can be changed by ongoing activation of the synaptic connections. This interesting property of synaptic plasticity allows for the modification of memories after they are recalled. One particular form of memory modification that is uniquely triggered by the recall of a memory is called “memory reconsolidation”. Memory reconsolidation can allow the updating, strengthening, or even the erasure of memory traces under certain conditions. However, very little is known about how reconsolidation functions at the level of synaptic connections between cells. This research program explores how reconsolidation affects the strength of synaptic connections between nerve cells. We seek to understand the mechanisms by which reconsolidation can lead to the modification and erasure of plastic changes in nerve connectivity, and how this process is regulated by previous and ongoing nerve activity. We will use a combination of advanced technical approaches to directly study the chemical connections between nerve cells, and use advanced genetic approaches to selectively activate and study reconsolidation at the synapse in single nerve cells. Additionally, we will identify key proteins that enable reconsolidation to erase memory traces, with the aim of manipulating these proteins to better understand how reconsolidation is activated. Overall these results will greatly enhance our understanding of how the flow of information is regulated in the brain and spinal cord. The study of how reconsolidation is activated at a synapse and how it regulates synaptic strength will yield new insights into how networks of neurons store, access, and update information.