Multiple forms of metaplasticity at a single hippocampal synapse during late postnatal development

• Metaplastic events occur at maturing Schaffer collateral synapses in the hippocampus.
• Presynaptic LTP declines as glutamate release probability increases with development.
• Postsynaptic LTP is facilitated by prolonged AMPAR responses with increasing age.
• Low frequency input prevents subsequent induction of LTP in more mature animals only.
• Developmental increases in theta power and action potential bursts promote LTP.

ABSTRACTMetaplasticity refers to adjustment in the requirements for induction of synaptic plasticity based on the prior history of activity. Numerous forms of developmental metaplasticity are observed at Schaffer collateral synapses in the rat hippocampus at the end of the third postnatal week. Emergence of spatial learning and memory at this developmental stage suggests possible involvement of metaplasticity in the final maturation of the hippocampus. Three distinct metaplastic phenomena are apparent. (1) As transmitter release probability increases with increasing age, presynaptic potentiation is reduced. (2) Alterations in the composition and channel conductance properties of AMPARs facilitate the induction of postsynaptic potentiation with increasing age. (3) Low frequency stimulation inhibits subsequent induction of potentiation in animals older but not younger than 3 weeks of age. Thus, many forms of plasticity expressed at SC-CA1 synapses are different in rats younger and older than 3 weeks of age, illustrating the complex orchestration of physiological modifications that underlie the maturation of hippocampal excitatory synaptic transmission. This review paper describes three late postnatal modifications to synaptic plasticity induction in the hippocampus and attempts to relate these metaplastic changes to developmental alterations in hippocampal network activity and the maturation of contextual learning.