Synaptic plasticity defect following visual deprivation in Alzheimer's disease model transgenic mice.
Amyloid-β (Aβ)-induced changes in synaptic function in experimental models of Alzheimer's disease (AD) suggest that Aβ generation and accumulation may affect fundamental mechanisms of synaptic plasticity. To test this hypothesis, we examined the effect of APP overexpression on a well characterized, in vivo, developmental model of systems-level plasticity, ocular dominance plasticity. Following monocular visual deprivation during the critical period, mice that express mutant alleles of amyloid precursor protein (APPswe) and Presenilin1 (PS1dE9), as well as mice that express APPswe alone, lack ocular dominance plasticity in visual cortex. Defects in the spatial extent and magnitude of the plastic response are evident using two complementary approaches, Arc induction and optical imaging of intrinsic signals in awake mice. This defect in a classic paradigm of systems level synaptic plasticity shows that Aβ overexpression, even early in postnatal life, can perturb plasticity in cerebral cortex, and supports the idea that decreased synaptic plasticity due to elevated Aβ exposure contributes to cognitive impairment in AD.
Neuropathology Service, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA.
Christopher M
CM
William
Mark L
ML
Andermann
Glenn J
GJ
Goldey
Demetris K
DK
Roumis
R Clay
RC
Reid
Carla J
CJ
Shatz
Mark W
MW
Albers
Matthew P
MP
Frosch
Bradley T
BT
Hyman
D000544:Alzheimer Disease / Q000235:genetics / Q000503:physiopathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D015353:Eye Enucleation; D005453:Fluorescence; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D010775:Photic Stimulation; D016133:Polymerase Chain Reaction; D053764:Presenilin-1 / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012683:Sensory Deprivation / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D014785:Vision, Ocular / Q000502:physiology*; D014793:Visual Cortex / Q000166:cytology / Q000502:physiology
D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1; D012333:RNA, Messenger