Synaptic Plasticity and Memory Formation
Abstract
The physiological effect known as long-term potentiation (LTP) is widely suspected of being the substrate of several forms of memory encoded by synapses in the forebrain of humans and other mammals. Work in the past year established that translational suppression with antisense oligonucleotides of one of the subunits of the AMPA (glutamate) transmitter receptor blocks the capacity of synapses to exhibit LTP. This confirms the hypothesis that the AMPA receptor is the agent of LTP expression. Changes in the waveform of the synaptic responses were found to occur in conjunction with LTP and were suggestive of a shift in the kinetic properties of the AMPA receptor channel. Computer simulations of the receptor led to the discovery that all known phenomenology of LTP expression can be reproduced by simply increasing the rates at which the receptor channel opens and closes. In parallel studies, a drug which acts on the AMPA receptor channel was shown to facilitate the induction of LTP. This led to a drug development program to find potent compounds of this kind which cross the blood-brain barrier and enhance the AMPA receptor and LTP in behaving rats. This effort was successful and one of the new drugs was then tested extensively in large numbers of rats across three learning tasks; as predicted, this compound produced substantial improvements in the encoding of short and long-term memories.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 30, 1993
- Accession Number
- ADA267988
Entities
People
- Gary Lynch
Organizations
- University of California, Irvine