Amyloid-β disrupts ongoing spontaneous activity in sensory cortex

Abstract

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.

Abnormal Population Responses in the Somatosensory Cortex of Alzheimer’s Disease Model Mice

“…***p < 0.001, Wilcoxon rank sum). Our results are in accordance with previous observations reported in studies using diverse strains of AD mice and various types of anesthesia 18 19 20 29 40 .…”

“…Synchronous activity is a fundamental feature in the operation of large cortical networks 61 62 63 64 . It has been shown that Aβ accumulation and plaques disrupt the synchrony of convergent inputs and reduce the ability of neurons to successfully integrate and propagate information 10 29 . In AD patients, there are large number of evidence for reduced neural synchrony during the resting state 22 .…”

“…VSDI enables simultaneous high spatial and temporal resolution (tens of micrometers per pixel; frame duration of ms) and high sensitivity to subthreshold synaptic potentials of populations of cortical neurons 25 26 27 28 . We hypothesized that in AD transgenic mice, aggregation of Aβ may induce disruption of functional columnar processing 23 24 29 . In this study, we imaged in vivo sensory evoked activity of large-scale networks in the barrel cortex of aged Tg mice and of non-transgenic control (Crtl) mice.…”

Connectivity of Pathology: The Olfactory System as a Model for Network-Driven Mechanisms of Alzheimer’s Disease Pathogenesis

“…According to the amyloid cascade hypothesis of AD pathogenesis (Hardy and Higgins, 1992 ), Aβ deposition in the brain triggers a series of events that ultimately leads to the development of the disease (Karran et al, 2011 ). For example, major downstream effects of Aβ deposition include synaptic and neuronal loss (Selkoe, 1991 ), as well as disruption to spontaneous activity of brain areas (Beker et al, 2014 ). This dysfunction is postulated to propagate to downstream neurons within the recurrent network (Beker et al, 2014 ), highlighting the idea that the olfactory system provides an ideal network for investigating mechanisms of AD pathogenesis.…”

“…For example, major downstream effects of Aβ deposition include synaptic and neuronal loss (Selkoe, 1991 ), as well as disruption to spontaneous activity of brain areas (Beker et al, 2014 ). This dysfunction is postulated to propagate to downstream neurons within the recurrent network (Beker et al, 2014 ), highlighting the idea that the olfactory system provides an ideal network for investigating mechanisms of AD pathogenesis.…”