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  3. Analysis of long-term potentiation (LTP) provides a powerful window into cellular mechanisms of learning and memory. Prior work shows late LTP (L-LTP), lasting three or more hours, first occurs at postnatal day 12 (P12) in Long-Evans rat hippocampus. The goal of the current work was to determine the developmental onset of L-LTP in mouse hippocampus as a basis for comparing potential effects of key genetic manipulations known to affect dendritic spine structure. Four mouse strains were tested. Both C57BL/6 and Fmr1-/y mice on the C57BL/6 background began to show reliable L-LTP at P35. In contrast, both 129SVE wild type andmore »Hevin- /- (Sparcl1-/-) on the 129SVE background first showed reliable L-LTP at P28. All strains showed a gradual progression between P10 to P28 in success rate for short-term potentiation (STP), which lasts one hour or less. At P10 in rats, two episodes of TBS result in L-LTP when he time between episodes was > 90 minutes. In mice, multiple bouts of TBS at various inter-bout intervals did not advance the onset age of L-LTP. Prior work in rats showed the onset of L-LTP at P12 coincided with the first formation of dendritic spines. In contrast, hippocampal dendritic spines are present by P24 in C57BL/6 mice, well before the onset age for L-LTP. These speciesdependent findings suggest that dendritic spines may be necessary but not sufficient for L-LTP.« less