The UCSF researchers conducted their study in cultured neurons of the hippocampus, a brain structure involved in learning and memory. They over-expressed the PSD-95 protein in their normal location, the post-synaptic membrane of neurons, at an early stage of glutamate synapse development.

They detected enhanced clustering and activity of glutamate synapse development, enhanced clustering and activity of glutamate receptors at the post-synaptic sites and an increase in the number and size of dendritic spines, which contain the receptors that respond to glutamate neurotransmitters.

More surprisingly, they discovered that PDS-95 stimulates maturation of the pre-synaptic terminal, which emits neurotransmitters, presumably by reaching across the synaptic cleft. They also determined the protein increases the release of glutamate neurotransmitters from the pre-synaptic terminal of the emitting neuron.

The findings suggest, says Bredt, that during normal conditions clustering of the protein at the post-synaptic site, which would cause maturation of the glutamate synapse, may be regulated during development and during learning processes and plasticity. The next step in the research, he says, is to try to understand at the molecular level what the PSD-95 protein targets to promote synaptic maturity and plasticity.

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Contact: Jennifer O'Brien
jobrien@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
16-Nov-2000