Age A
Basal synaptic transmission Presynaptic function LTP LTD Other Reference PS1 cKO 3–6 mo Cortical A
and A
are decreased Normal (CA1) Normal PPF ratio (CA1) Normal (CA1) (5x TBS) normal (CA1) (3x 100 Hz) Normal (CA1) [178 ] 2 mo Normal (CA1) Decreased PPF ratio (CA1) Decreased (CA1) (5x TBS) Normal (CA1) Reduced NMDAR function (CA1); decreased cortical synaptic levels of NR1, NR2A, α CaMKII, and CRE-dependent genes
[179 ] 6 mo Increased (CA1) Decreased PPF ratio (CA1) Decreased (CA1) (5x TBS) Normal (CA1) PS cDKO 2 mo Increased expression of the NR2A subunit of NMDARs, specifically at postsynaptic density and presynaptic terminals of axo/dendritic synapses, trapped at synapses (CA1) [180 ] 5 wk Decreased Ca2+ -dependent frequency facilitation and release probability (CA1) Normal (CA1) (5x TBS) Normal NMDAR-mediated synaptic response (CA1)
[181 ] 6 wk Decreased (CA1) 5x TBS Reduced NMDAR-mediated synaptic response (CA1) CA1-PS cDKO 2 mo Normal (CA1) Normal (CA1) (5x TBS) Normal NMDAR/AMPAR ratio [182 ] CA3-PS cDKO 2 mo Decreased Ca2+ -dependent frequency facilitation and release probability (CA1) Decreased (CA1) (5x TBS) Normal NMDAR/AMPAR ratio
[182 ]
AppTg (Swe/Ind) 3 mo Normal (CA1) Normal (CA1) Increased (CA1) (5x TBS)
[183 ] 6 mo Age dependent increase in Aβ levels and plaque deposition Decreased (CA1) Normal (CA1) Decreased (CA1) (5x TBS)
AppTg; PS1−/− 3 mo Normal (CA1) Normal (CA1) Increased (CA1)
[183 ] 6 mo Decreased cortical Aβ peptides and plaque formation Decreased (CA1) Normal (CA1) Decreased (CA1) (5x TBS) 3-4 mo Normal (CA1) Normal (CA1) Tg2576 6-7 mo 50% increase in soluble Aβ Decreased (CA1)-stronger stimulus required to elicit similar sized postsynaptic responses Decreased (CA1)
[184 ] 14-15 mo 1000% increase in soluble A
Decreased (CA1) but similar to 6-7 months Normal (CA1) Tg2576 w/MRK-560 (
-secretase inhibitor) 6-7 mo 1, 3, or 7 days of treatment reduced soluble A
levels Partial recovery but not significant Recovered (CA1)
[184 ] 15 mo 3 months of treatment reduced soluble A
levels No improvement Tg2576 w/CHF5074 (
-secretase modulator) 6 mo 4-week, subchronic, oral treatment reduced A
levels Recovered (CA1) [185 ]