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2009 Grants - Fa
LTP and Memory Impairment by Prolonged Exposure to Picomolar Beta-amyloid
Mauro Fa, Ph.D.
Columbia University Medical Center
New York, New York
2009 New Investigator Research Grant
Nerve cells send signals to one another through specialized structures called synapses. The strength of the signal sent through a synapse can change in response to previous events, and such changes are thought to mediate some forms of learning and memory. Long-term potentiation (LTP) is an example of an increase in synaptic strength that occurs in response to previous activity at the same synapse. It is widely studied in a part of the brain called the hippocampus.
Scientists have observed that low concentrations of beta-amyloid, a protein fragment thought to mediate some of the adverse effects of Alzheimer's disease, causes a reduction in the ability of hippocampal synapses to exhibit LTP. However, even lower concentrations of beta-amyloid applied briefly seem to increase LTP at these synapses. Mauro Fa, Ph.D. has made an observation that may explain this discrepancy: application of very low concentrations of beta-amyloid for prolonged periods of time reduces LTP.
Dr. Fa and colleagues have proposed to study how the structure and function of synapses change when they are exposed to very low concentrations of beta-amyloid for prolonged periods of time, as might occur in the early stages of Alzheimer's disease. The researchers will examine how such exposure changes the spontaneous release of neurotransmitter packets, the fundamental chemical unit that synapses use to send signals to nearby nerve cells. They will also examine how exposure to beta-amyloid changes the distribution of proteins at the synapse as well as the microscopic structure of the synapse. The researchers will correlate these findings with changes in the ability of the synapses to store memory. These studies may help to explain some of the events occurring in the brain during the earliest stages of disease onset.