Developmental onset of enduring long-term potentiation in mouse hippocampus

Abstract

Running Title: Developmental onset of L-LTP in mouse hippocampus KEY POINTS SUMMARY (150 words max, currently 150, 5 bullets)• Saturating theta-burst stimulation (TBS) was used to discern the developmental age when short-term potentiation (STP) lasting 1 hour and late long-term potentiation (L-LTP) lasting >3 hr are first expressed in mouse hippocampus. • Four mouse strains were compared-C57BL/6 and Fmr1 -/y on C57BL/6 background and 129SVE and Hevin -/-(Sparcl1 -/-) on 129SVE background-because both gene manipulations alter dendritic spines. • In all four strains, STP onset was gradual, first occurring between postnatal days (P) 10-28, while reliable L-LTP emerged in C57BL/6 and Fmr1 -/y at P35, and in 129SVE and Hevin -/-(Sparcl1 -/-) at P28. • In contrast to rat hippocampus, multiple episodes of TBS did not alter the onset age of L-LTP in mouse hippocampus. • The L-LTP onset age in rat hippocampus is P12, coincident with the first appearance of dendritic spines. Others report spine appearance by P24 in mouse hippocampus, suggesting spines may be necessary but not sufficient for L-LTP. ABSTRACT (250 words max, currently 243)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 and 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 the 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.Animals. Breeding pairs of C57BL/6 (RRID:IMSR_JAX:000664) and Fmr1 -/y (RRID:MGI:5703659) on this background were kindly donated by Dr. D. Brager (Center for Learning and Memory, University of Texas at Austin) who received the founder pair from Dr. K. Huber (University of Texas Southwestern). Breeding pairs of 129SVES6 mice were obtained from a supplier (Taconic, Rensselaer, NY; RRID:IMSR_TAC:129sve) and Hevin -/-(Sparcl1 -/-, allelic composition Sparcl1 tm1Pmc /Sparcl1 tm1Pmc , RRID:MGI:4454665) were on this background. We wil...

Synaptic Odyssey

“…Thus, in contrast to adult rat hippocampus, where synapse enlargement is balanced by stalled spine outgrowth, LTP enhances synaptogenesis in favor of circuit production during development. It remains to be determined whether species-and straindependent differences in LTP onset between mice, and in rats, can be accounted for by variance in the onset age of spinogenesis (Ostrovskaya et al, 2019).…”