title: Orchestrated experience-driven Arc responses are disrupted in a mouse model of Alzheimer's disease.
abstract: Experience-induced expression of immediate-early gene Arc (also known as Arg3.1) is known to be important for consolidation of memory. Using in vivo longitudinal multiphoton imaging, we found orchestrated activity-dependent expression of Arc in the mouse extrastriate visual cortex in response to a structured visual stimulation. In wild-type mice, the amplitude of the Arc response in individual neurons strongly predicted the probability of reactivation by a subsequent presentation of the same stimulus. In a mouse model of Alzheimer's disease, this association was markedly disrupted in the cortex, specifically near senile plaques. Neurons in the vicinity of plaques were less likely to respond, but, paradoxically, there were stronger responses in those few neurons around plaques that did respond. To the extent that the orchestrated pattern of Arc expression reflects nervous system responses to and physiological consolidation of behavioral experience, the disruption in Arc patterns reveals plaque-associated interference with neural network integration.
authors.affiliation: Alzheimer's Disease Research Laboratory, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.
authors.forename: Nikita
authors.initials: N
authors.lastname: Rudinskiy
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Hawkes
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Betensky
authors.forename: Megumi
authors.initials: M
authors.lastname: Eguchi
authors.forename: Shun
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: Tara L
authors.initials: TL
authors.lastname: Spires-Jones
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Hyman
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D003598:Cytoskeletal Proteins / Q000096:biosynthesis*; D004195:Disease Models, Animal; D051379:Mice; D008822:Mice, Transgenic; D036641:Microscopy, Fluorescence, Multiphoton / Q000379:methods; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D009474:Neurons / Q000378:metabolism; D010775:Photic Stimulation / Q000379:methods; D058225:Plaque, Amyloid / Q000378:metabolism; D014793:Visual Cortex / Q000378:metabolism*
chemical_list: D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; C092069:activity regulated cytoskeletal-associated protein