Learning and memory are processes that link experience with behavior and therefore play central roles in our daily experience. That there exists a physical basis for these processes seems at first hard to imagine--except for the fact that physical disruptions in the brain, such as stroke or disease, can make them go wrong. This week, researchers report that by making targeted genetic disruptions that disable a key neurotransmitter receptor in the fruit fly, they have uncovered an important clue to the physiological mechanisms at work in learning and memory.

The subject of the study was the so-called NMDA receptor--a neurotransmitter receptor possessing special properties that could make it especially useful in learning and memory. In particular, past work has shown that NMDA receptors can respond in a special way to concurrent events on both sides of a synapse. Acting in this way as "coincidence detectors," NMDA receptors may help neurons form stronger or weaker connections with each other depending on whether they are repeatedly stimulated together. Neuroscientists strongly suspect that this process--called synaptic plasticity--of modulating the strength of synaptic connections on the basis of experience forms an elemental, neuron-level basis for learning and memory.

In the new work, the researchers sought to overcome technical hurdles that have stood in the way of understanding when and how NMDA receptors function in learning and memory. The research team, led by Tim Tully of Cold Spring Harbor Laboratory and Ann-Shyn Chiang of National Tsing Hua University, Taiwan, first used a genetic mutation to show that NMDA receptors are required for associative, or Pavlovian, learning in the fruit fly; they then went on to show that these receptors are not just passively participating but are in fact actively needed for both associative learning and long-term memory. The researchers demonstrated this active requirement by molecularly disrupting previously
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Contact: Heidi Hardman
hhardman@cell.com
1-617-397-2879
Cell Press
11-Apr-2005

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