title: Amyloid-β disrupts ongoing spontaneous activity in sensory cortex.
abstract: The effect of Alzheimer's disease pathology on activity of individual neocortical neurons in the intact neural network remains obscure. Ongoing spontaneous activity, which constitutes most of neocortical activity, is the background template on which further evoked-activity is superimposed. We compared in vivo intracellular recordings and local field potentials (LFP) of ongoing activity in the barrel cortex of APP/PS1 transgenic mice and age-matched littermate CONTROLS, following significant amyloid-β (Aβ) accumulation and aggregation. We found that membrane potential dynamics of neurons in Aβ-burdened cortex significantly differed from those of nontransgenic
  
  
  METHODS
  durations of the depolarized state were considerably shorter, and transitions to that state frequently failed. The spiking properties of APP/PS1 neurons showed alterations from those of
  
  
  METHODS
  both firing patterns and spike shape were changed in the APP/PS1 group. At the population level, LFP recordings indicated reduced coherence within neuronal assemblies of APP/PS1 mice. In addition to the physiological effects, we show that morphology of neurites within the barrel cortex of the APP/PS1 model is altered compared to CONTROLS. These results are consistent with a process where the effect of Aβ on spontaneous activity of individual neurons amplifies into a network effect, reducing network integrity and leading to a wide cortical dysfunction.
authors.affiliation: Gonda Brain Research Center, Bar-Ilan University, 52900, Ramat Gan, Israel.
authors.forename: Shlomit
authors.initials: S
authors.lastname: Beker
authors.affiliation: Gonda Brain Research Center, Bar-Ilan University, 52900, Ramat Gan, Israel.
authors.forename: Miri
authors.initials: M
authors.lastname: Goldin
authors.affiliation: Gonda Brain Research Center, Bar-Ilan University, 52900, Ramat Gan, Israel.
authors.forename: Noa
authors.initials: N
authors.lastname: Menkes-Caspi
authors.affiliation: Gonda Brain Research Center, Bar-Ilan University, 52900, Ramat Gan, Israel.
authors.forename: Vered
authors.initials: V
authors.lastname: Kellner
authors.affiliation: Gonda Brain Research Center, Bar-Ilan University, 52900, Ramat Gan, Israel.
authors.forename: Gal
authors.initials: G
authors.lastname: Chechik
authors.affiliation: Gonda Brain Research Center, Bar-Ilan University, 52900, Ramat Gan, Israel. sterned@mail.biu.ac.il.|Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Charlestown, MA, USA. sterned@mail.biu.ac.il.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Stern
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D008297:Male; D008564:Membrane Potentials; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010296:Parietal Lobe / Q000378:metabolism / Q000473:pathology; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D013003:Somatosensory Cortex
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor
keywords: Alzheimer’s disease; Firing patterns; LFP; Membrane potential; Plaques; Synaptic summation