Learning discloses abnormal structural and functional plasticity at hippocampal synapses in the APP23 mouse model of Alzheimer's disease.
B6-Tg/Thy1APP23Sdz (APP23) mutant mice exhibit neurohistological hallmarks of Alzheimer's disease but show intact basal hippocampal neurotransmission and synaptic plasticity. Here, we examine whether spatial learning differently modifies the structural and electrophysiological properties of hippocampal synapses in APP23 and wild-type mice. While no genotypic difference was found in the pseudotrained mice, training elicited a stronger increase in spine density and a more rapid decay of long-term potentiation (LTP) in APP23 mutants. Thus, learning discloses mutation-related abnormalities regarding dendritic spine formation and LTP persistence, thereby suggesting that although unaltered in naïve synapses, plasticity becomes defective at the time it comes into play.
Middei
Silvia
S
CNR Institute for Neuroscience, S. Lucia Foundation, Rome 00143, Italy. s.middei@hsantalucia.it
Roberto
Anna
A
Berretta
Nicola
N
Panico
Maria Beatrice
MB
Lista
Simone
S
Bernardi
Giorgio
G
Mercuri
Nicola B
NB
Ammassari-Teule
Martine
M
Nisticò
Robert
R
D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000704:Analysis of Variance; D000818:Animals; D001703:Biophysics / Q000379:methods; D049229:Dendritic Spines / Q000473:pathology / Q000648:ultrastructure; D004195:Disease Models, Animal; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D066298:In Vitro Techniques; D007859:Learning Disabilities / Q000209:etiology* / Q000235:genetics; D008124:Locomotion / Q000235:genetics; D017774:Long-Term Potentiation / Q000235:genetics*; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000473:pathology / Q000648:ultrastructure; D018408:Patch-Clamp Techniques / Q000379:methods; D011930:Reaction Time / Q000235:genetics; D016622:Silver Staining / Q000379:methods; D013997:Time Factors
D016564:Amyloid beta-Protein Precursor