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The Journal of Neuroscience, December 3, 2003, 23(35):11142-11146

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Maturation of Long-Term Potentiation Induction Rules in Rodent Hippocampus: Role of GABAergic Inhibition

Rhiannon M. Meredith, Anna M. Floyer-Lea, and Ole Paulsen

University Laboratory of Physiology, Oxford University, Oxford, OX1 3PT, United Kingdom

The induction rules of synaptic plasticity are important for the functional operation of a neural network. We asked whether such synaptic plasticity rules change during development from juvenile to adult animals. Using perforated patch and whole-cell recordings from CA1 pyramidal cells in hippocampal slices, we demonstrate here that the postsynaptic requirements for induction of associative long-term potentiation (LTP) shift gradually. Presynaptic stimulation paired with single postsynaptic action potentials became progressively less effective at inducing LTP with advancing developmental age until, in adult hippocampus, postsynaptic bursts of action potentials were necessary to induce synaptic potentiation. This developmental change might be accounted for by changes in GABA_A receptor-mediated inhibition known to occur in the hippocampus during this postnatal period, because blocking GABA_A receptor-mediated inhibition re-established the effectiveness of single postsynaptic action potentials at inducing LTP in adult hippocampus. These data reveal a gradual shift in the induction rules for LTP, explained by a maturational change in GABAergic inhibition, and could have implications for our understanding of the role of inhibition in information processing in the brain.

Key words: rat; mouse; hippocampus; CA1; development; synaptic plasticity; long-term potentiation; inhibition; GABA_A receptor; Hebbian; associative LTP

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Received June 27, 2003; revised September 29, 2003; accepted October 3, 2003.

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