Abstract
Long-term potentiation (LTP) is thought to be critically involved not only in learning and memory, but also during the activity-dependent developmental phases of neural circuit formation and refinement1,2. Whether the mechanisms underlying LTP change during this phase of postnatal development, however, is unknown. We report here that, unlike LTP in the more mature CA1 region of the hippocampus, LTP in neonatal rodent hippocampus (<9 postnatal days, <P9) requires cyclic AMP–dependent protein kinase A (PKA) but not Ca2+/calmodulin-dependent protein kinase II (CaMKII).
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Supplementary Fig. 1.
LTP is present at thalamocortical synapses in CaMKII(T286A) mutant mice. (a) Graph showing changes in neocortical CaMKII activity as a function of postnatal age. Values are expressed as a percentage of adult activity (>P60). (b) Example of LTP at thalamocortical synapses onto a layer IV neuron in P5 barrel cortex from a homozygous mutant animal. Inset shows sample EPSCs before and after pairing. (Calibration bars: 10 pA, 10 msec) (c) Summary of LTP at thalamocortical synapses in P4-7 homozygote CaMKII(T286A) mice (n=7). (d) Comparison of LTP magnitude in wild-type mice (n=34; some data from2), heterozygote CaMKII(T286A) mutant mice (n=3) and homozygote CaMKII(T286A) mutant mice (n=7). (GIF 8 kb)
Supplementary Fig. 2.
P42/44 MAPK is required for LTP in mature but not in neonatal hippocampus. (a) Example (1) and summary (2) of effects of the p42/44 MAPK cascade inhibitor PD98059 on LTP in P7-8 hippocampus (Control, n=7; PD98059, n=8). (b) Example (1) and summary (2) of effects of PD98059 on LTP in P>27 hippocampus (Control, n=6; PD98059, n=5). (GIF 11 kb)
Supplementary Fig. 3.
PKA activation increases mEPSC amplitude in neonatal but not in mature hippocampus. (a) Example of mEPSCs before and after forskolin treatment in P7 and P27 hippocampus. Four consecutive traces in each condition are shown (Calibration bars; 20 pA, 1 sec). (b) Averaged mEPSC (n=300-500) before and after forskolin treatment. (c) Summary of effects of forskolin on frequency and amplitude of mEPSCs in P7,8 and >P26 hippocampus. (PDF 593 kb)
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Yasuda, H., Barth, A., Stellwagen, D. et al. A developmental switch in the signaling cascades for LTP induction. Nat Neurosci 6, 15–16 (2003). https://doi.org/10.1038/nn985
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DOI: https://doi.org/10.1038/nn985
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