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Expression mechanisms underlying NMDA receptor-dependent long-term potentiation.
1Department of Cellular and Molecular Pharmacology, University of California, San Francisco 94143-0450, USA. nicoll@phy.ucsf.edu
Annals of the New York Academy of Sciences
|July 22, 1999
Summary
Long-term potentiation (LTP), a cellular model for memory, primarily involves postsynaptic changes, not increased glutamate release. This suggests that silent synapses becoming active is key to memory formation.
Area of Science:
- Neuroscience
- Cellular Biology
- Molecular Biology
Background:
- Long-term potentiation (LTP) is a key cellular model for learning and memory.
- LTP induction in the hippocampus requires postsynaptic calcium influx via NMDA receptors.
- The precise mechanisms of LTP expression remain incompletely understood.
Purpose of the Study:
- To investigate the site of LTP expression, focusing on presynaptic versus postsynaptic mechanisms.
- To review experimental evidence gathered over the past decade regarding LTP expression.
- To differentiate between glutamate release and postsynaptic sensitivity changes in LTP.
Main Methods:
- Analysis of dual-component excitatory postsynaptic currents (EPSCs).
- Paired-pulse facilitation and release probability measurements.
- Assessment of miniature EPSC amplitudes and synaptic potency.
- Investigation of CaM kinase II activation and silent synapse function.
Main Results:
- Experimental evidence largely refutes a presynaptic expression mechanism for LTP.
- Multiple findings support a postsynaptic expression mechanism for LTP.
- The decrease in synaptic failures during LTP can be explained by postsynaptically silent synapses becoming functional.
Conclusions:
- LTP expression is predominantly mediated by postsynaptic mechanisms.
- Presynaptic changes, such as increased glutamate release, are unlikely to be the primary drivers of LTP.
- Future research should explore activity-dependent receptor targeting and AMPA receptor phosphorylation.