A Unified Model of the Presynaptic and Postsynaptic Changes During LTP at CA1 Synapses

John Lisman^1* and Sridhar Raghavachari^2*

¹Department of Biology, Brandeis University, Waltham, MA 02454, USA.
²Box 3209, Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA.

Gloss: Long-term potentiation (LTP) is an activity-dependent process that leads to a long-lasting increase in the strength of synapses. Such changes are thought to underlie the storage of memory in the brain. But what exactly determines the strength of a synapse, and how is its strength enhanced during LTP? We review a large body of work on LTP at synapses in the hippocampal CA1 region, the site at which LTP has been most extensively studied. Experiments indicate that there are both presynaptic processes that enhance the release of neurotransmitter (glutamate) and postsynaptic processes that enhance the response to transmitter. To understand how these processes work together, we developed a structural model according to which the synapse is composed of transsynaptic modules. The synapse can be partially silent, meaning that some modules contribute to AMPA-mediated transmission whereas others do not (although all modules contribute to NMDA-mediated transmission). Within this framework, we have formulated a model that accounts for a large set of data in a unified way.

*Corresponding author. E-mail, lisman{at}brandeis.edu; sri{at}neuro.duke.edu

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