Developmental Regulation of the Late Phase of Long-term Potentiation (l-ltp) 1 and Metaplasticity in Hippocampal Area Ca1 of the Rat 2 Running Head (67 Characters including Spaces): L-ltp and Metaplasticity during 3 Development in Hippocampal Area Ca1 4

(243 words) 21 Long-term potentiation (LTP) is a form of synaptic plasticity thought to underlie 22 memory; thus, knowing its developmental profile is fundamental to understanding 23 function. Like memory, LTP has multiple phases with distinct timing and mechanisms. 24 The late phase of LTP (L-LTP), lasting longer than 3 hours, is protein synthesis-25 dependent and involves changes in the structure and content of dendritic spines, the 26 major sites of excitatory synapses. In previous work, tetanic stimulation first produced L-27 LTP at postnatal day 15 (P15) in area CA1 of rat hippocampus. Here we used a more 28 robust induction paradigm involving theta-burst stimulation (TBS) in acute slices and 29 found the developmental onset of L-LTP to be three days earlier at P12. In contrast, at 30 P8-11, TBS only reversed the synaptic depression that occurs from test pulse 31 stimulation in developing (P8-15) hippocampus. A second bout of TBS delivered 30-180 32 minutes later produced L-LTP at P10-11 but not at P8-9, and enhanced L-LTP at P12-33 15. Both the developmental onset and the enhanced L-LTP produced by repeated bouts 34 of TBS were blocked by the NMDA receptor antagonist APV. Thus, the developmental 35 onset age is P12 for L-LTP induced by the more robust and perhaps more naturalistic 36 TBS induction paradigm. Metaplasticity produced by repeated bouts of TBS is 37 developmentally regulated, advancing the capacity for L-LTP from P12 to P10, but not 38 to younger ages. Together these findings provide a new basis from which to investigate 39 mechanisms that regulate the developmental onset of this important form of synaptic 40 plasticity.