We will identify the molecules and mechanisms in the brain that underlie learning and memory. We will determine how errors in the process of brain cell signaling and flexibility contribute to major brain disorders.
Brain cells (neurons) relay information by way of their connections, known as synapses. Information is encoded via changes in the strength of the synapses. The two most extensively studied forms of synaptic plasticity are long-term depression (LTD) and long-term potentiation (LTP). This dynamic, bi-directional process of weakening and strengthening is known as synaptic plasticity.
Synaptic plasticity is a normal physiological process that is necessary for synapse development and for learning and memory throughout the life-span. LTD for example involves the weakening of synaptic transmission and can lead to physiological synaptic elimination (pruning). LTD is normally tightly regulated but in numerous brain disorders this regulation likely breaks down, due to genetic and/or environmental causes.
Errors in synaptic plasticity processes may cause or contribute to many brain disorders, such as dementia (including the most common form Alzheimer’s Disease, AD), Multiple Sclerosis (MS), psychiatric disorder, and Autism Spectrum Disorder (ASD). Cognitive deficits that are associated with these and other disorders are due, at least in part, to an imbalance between LTP and LTD. Aggressive LTD may explain both cognitive deficits and synapse loss.
We expect to obtain novel information relevant to the understanding of brain function in health and disease. The new knowledge will be used to develop effective treatments for some of the major health issues facing patients with devastating brain disorders. We will build on past successes; for example, we identified the NMDA receptor as the trigger for major forms of synaptic plasticity and several effective medications work via modulation of NMDA receptor-mediated synaptic plasticity.