Developmental regulation of the late phase of long-term potentiation (L-LTP) and metaplasticity in hippocampal area CA1 of the rat

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Abstract
Long-term potentiation (LTP) is a form of synaptic plasticity thought to underlie memory; thus knowing its developmental profile is fundamental to understanding function. Like memory, LTP has multiple phases with distinct timing and mechanisms. The late phase of LTP (L-LTP), lasting longer than 3 h, is protein synthesis dependent and involves changes in the structure and content of dendritic spines, the major sites of excitatory synapses. In previous work, tetanic stimulation first produced L-LTP at postnatal day 15 (P15) in area CA1 of rat hippocampus. Here we used a more robust induction paradigm involving theta-burst stimulation (TBS) in acute slices and found the developmental onset of L-LTP to be 3 days earlier at P12. In contrast, at P8–11, TBS only reversed the synaptic depression that occurs from test-pulse stimulation in developing (P8–15) hippocampus. A second bout of TBS delivered 30–180 min later produced L-LTP at P10–11 but not at P8–9 and enhanced L-LTP at P12–15. Both the developmental onset and the enhanced L-LTP produced by repeated bouts of TBS were blocked by the N-methyl-d-aspartate receptor antagonist dl-2-amino-5-phosphonovaleric acid. Thus the developmental onset age is P12 for L-LTP induced by the more robust and perhaps more naturalistic TBS induction paradigm. Metaplasticity produced by repeated bouts of TBS is developmentally regulated, advancing the capacity for L-LTP from P12 to P10, but not to younger ages. Together these findings provide a new basis from which to investigate mechanisms that regulate the developmental onset of this important form of synaptic plasticity.