Imaging Synaptic Specificity at Dendritic Spines

Adam Carter, Ph.D.

New York University School of Medicine

Funded in June, 2010: $200000 for 3 years
LAY SUMMARY .

LAY SUMMARY

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Seeing how synapses are lost in Parkinson’s disease may lead to development of targeted therapies

This cellular imaging study in normal mice and in those with Parkinson’s disease will help identify how electrochemical communication between brain cells normally occurs, and how this communication is altered in Parkinson’s disease.

Parkinson’s disease occurs when brain cells that produce the chemical messenger dopamine die. These cells are located in a deep brain structure called the “Substantia Nigra.” The cells’ axons (communication cables) project into the brain’s “striatum,” which controls movement. Each of these brain cells passes its electrochemical messages, via dopamine, down its axon. Dopamine is then released and is taken up by a nearby brain cell’s tiny “dendritic spines.” This process called synaptic transmission. The dentritic spines then pass the message to the cell body to complete the communication chain, and this brain cell then uses the same synaptic transmission process to send the message along to the next one. The investigators hypothesize that certain dendritic spines are highly specific for dopamine transmission, and that when these dendritic spines are altered, Parkinson’s disease occurs.

They cannot test this hypothesis in Parkinson’s disease patients because the brain areas are located so deep in the brain that these cellular processes cannot be visualized with current imaging technologies. Instead, they will use a combination of two-photon cellular imaging, optogenetics and electrophysiology recordings to compare synaptic transmission events in normal mice and in a mouse model of Parkinson’s disease.

Significance:  By determining which synapses are lost in Parkinson’s disease, the study may lead to therapies that are targeted to preventing the loss of these synapses.