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The Journal of Neuroscience, May 26, 2004, 24(21):4903-4911; doi:10.1523/JNEUROSCI.0170-04.2004

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Cellular/Molecular
Multiple, Developmentally Regulated Expression Mechanisms of Long-Term Potentiation at CA1 Synapses

Mary J. Palmer, John T. R. Isaac, and Graham L. Collingridge

The Medical Research Council Centre for Synaptic Plasticity, Department of Anatomy, University of Bristol, Bristol, BS8 1TD, United Kingdom

Long-term potentiation (LTP) of AMPA receptor-mediated synaptic transmission at hippocampal CA1 synapses has been extensively studied, but the mechanisms responsible for its expression remain unresolved. We tested a hypothesis that there are multiple, developmentally regulated expression mechanisms by directly comparing LTP in hippocampal slices obtained from rats of two ages. At postnatal day 12 (P12), LTP was fully accounted for by an increase in potency (mean amplitude of responses excluding failures). This was associated with either an increase in AMPA receptor single-channel conductance () or no change in , suggesting an increase in the number of AMPA receptors. At P6, LTP was explained by an additional two mechanisms. In the majority of neurons, LTP was associated with an increase in success rate and a decrease in paired-pulse facilitation. In the remaining neurons, LTP was attributable to an increase in potency. However, in contrast to P12 neurons, the potency increase was associated with a decrease in , suggesting the insertion of receptors with lower . We conclude that there are multiple expression mechanisms for LTP at CA1 synapses that are developmentally regulated. These findings suggest that a single class of synapse uses a number of different molecular mechanisms to produce long-term changes in synaptic strength.

Key words: CA1; LTP; development; probability of release; AMPA receptor; conductance

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Received Jan 16, 2004; revised March 31, 2004; accepted April 1, 2004.

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