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Novel approaches to understand the role of cAMP and co-signaling cascades in synaptic plasticity and brain disorders

Principal Investigator:
  • Graham Collingridge, Mount Sinai
Team Members:
  • Kenichi Okamato, Mount Sinai
  • Min Zhuo, University of Toronto
  • Zhengping Jia, The Hospital For Sick Children
  • Peter St. George-Hyslop, University of Toronto
  • Mount Sinai Hospital Foundation of Toronto

Project Overview

Synaptic plasticity is the process where the strength of connections between nerve cells is altered by experience. It is widely believed that synaptic plasticity is used to store information in the brain and is important for learning and memory and other major cognitive processes. The most widely studied form of synaptic plasticity, long-term potentiation (LTP), is a highly complex process which is starting to be understood in some detail. It is believed that errors in this process may explain the cognitive deficits that are associated with major brain disorders such as Alzheimer’s disease and other serious conditions as diverse as chronic pain and anxiety. Therefore understanding LTP is important for not only understanding how our brains store memories but also for developing better treatments for major brain disorders. Dr. Collingridge and his team plan to exploit and further develop novel methods to to study LTP at the level of individual nerve connections with an unprecedented level of resolution. They will use newly developed probes and optical methods for studying some of the biochemical processes that we believe are fundamentally important for LTP. The funding will allow the multidisciplinary team to design and build new probes and modulators of the signaling cascades we believe are dysfunctional in brain disease and chronic pain. They will use state-of-the-art imaging, genetics, and electrophysiology methods to understand the mechanisms of LTP at a greater resolution than hitherto possible. They will also use these methods to decipher how these processes may go wrong in three major disorders that have a huge negative impact on society: Alzheimer’s disease, chronic pain and chronic anxiety.