john lismanJohn Lisman, Ph.D.
Professor of Biology
Amplification and Switching in Signal Transduction and Memory

Ph.D., Massachusetts Institute of Technology

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My laboratory is interested in two questions: the mechanisms of memory in the brain and the mechanisms of phototransduction in photoreceptors. In both cases, we seek to determine how chemical and electrical processes can work as a system to perform physiological function.

We are using the rat brain slice to study activity-dependent synaptic plasticity. Most recently, we found that plasticity is greatly heightened during a cholinergically-induced theta-frequency oscillation of the hippocampal network. As a step in this direction, we have developed a means of monitoring individual synapses in the dendrites using Ca2+-sensitive dyes and optical detection methods. Theoretical studies are also being done in an attempt to explore the possible relationship of brain oscillations to memory events. Most recently, it has become possible to test various theories by measuring oscillations from the brain surface of patients being treated for epilepsy. These patients are willing to do standard memory tests and we can directly measure what is going on in their brains during these tests.

A related question of interest is the molecular basis of memory. We have done theoretical work suggesting that the repository of synaptic memory may be the calcium/calmodulin dependent protein kinase II contained within a synaptic structure called the postsynaptic density. There is now substantial support for this model and we are attempting further tests. The processes of synaptic plasticity are not fixed, but rather can be altered by neuromodulators. Our recent work shows that dopamine can affect both the strengthening and weakening of synapses.

In the area of phototransduction, a central problem is the elucidation of the cascade reactions by which a single photon absorbed by rhodopsin activates thousands of channels. We have obtained evidence for the involvement of Ca2+ released by G protein, phospholipase-C, IP3 cascade. However, we have evidence that the channels are directly opened by cGMP. Thus, the current problem is to understand how cGMP might be generated by Ca2+. This marvelous cascade provides the opportunity to study other interesting reactions such as modulation of rhodopsin deactivation and the role of GTP hydrolysis.

Recent Publications:

415 South Street, Waltham, MA 02453 (781) 736-2000