LeDoux Lab 2004 SfN Abstracts

MOLECULAR MECHANISMS OF LEARNING INDUCED SYNAPTIC PLASTICITY IN VIVO.
S.Rumpel1*; J.LeDoux2; A.Zador1; R.Malinow1
1. Dept Neurosci, Cold Spring Harbor Lab, Cold Spring Harbor, NY, USA 2. Ctr. for Neural Sci., New York Univ., New York, NY, USA
How does the brain store information for long periods of time? We have tested the hypothesis that long-term changes in the efficacy of synaptic transmission are a mechanism of memory formation. To detect synaptic plasticity in the living brain we have utilized the recent finding that potentiated synapses show an increased amount of GluR1 subunit containing AMPA receptors. This GluR1 containing type of AMPA receptors is additionally incorporated into synapses during long-term potentiation and accounts at least in part for the increase in synaptic efficacy. We used a herpes-simplex virus based system to overexpress AMPA receptor GluR1 subunits in neurons of the lateral amygdala, a structure known to be essential for memory formation during cued classical fear conditioning. We found increased synaptic incorporation of recombinant GluR1 receptors in rats that received paired training (tones and footshocks) as compared to animals from the unpaired control group. In a second experimental series we blocked synaptic incorporation of GluR1 containing AMPA receptors by viral overexpression of a crucial fragment of the receptor. Fear memory was severely impaired in those animals as compared to animals injected with a control virus. We conclude that the long-term synaptic plasticity dependent on GluR1 delivery to synapses is critical to memory formation in the lateral amygdala during fear conditioning. Additionally, we conclude that the use of tagged AMPA receptors is a powerful tool to detect synaptic plasticity in the living brain and to functionally label the elements of neuronal circuits that undergo changes during memory formation. Support Contributed By: DFG, NIH
Program No. 971.12 Poster presentation:Wednesday, Oct. 27, 4:00 PM - 5:00 PM Location: U13