Abstract
While the link between amyloid β (Aβ) accumulation and synaptic degradation in Alzheimer’s disease (AD) is known, the consequences of this pathology on population coding remain unknown. We found that the entropy, a measure of the diversity of network firing patterns, was lower in the dorsal CA1 region in the APP/PS1 mouse model of Aβ pathology, relative to controls, thereby reducing the population’s coding capacity. Our results reveal a network level signature of the deficits Aβ accumulation causes to the computations performed by neural circuits.
Highlights
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder associated with cognitive decline that is thought to arise in part from the pathological accumulation of amyloid β (Aβ) plaques[1] throughout the neocortex and hippocampus
We identified spike waveforms for individual representative units on a single probe shank for a control (Fig. 1b) and APP/PS1 (Fig. 1k) by concatenating putative spikes across neighboring channels, projecting the concatenated waveforms onto a low-dimensional space using principal components analysis (PCA), and identifying clusters using a mixture of Gaussians model[27] (Fig. 1c,l)
When we examined the spike waveforms from the units isolated in the control and the APP/PS1 animals, we found no significant differences (Fig. S4), suggesting that there was no bias indicative of different types of neurons being sampled between control and APP/PS1 mice
Summary
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder associated with cognitive decline that is thought to arise in part from the pathological accumulation of amyloid β (Aβ) plaques[1] throughout the neocortex and hippocampus. Aβ pathology has been linked to various behavioral and cognitive changes[4,5]; for example in mouse models, plaque burden correlates with degradation of place fields in the dorsal CA1 (dCA1) subfield of the hippocampus, and is associated with poor performance on spatial memory tasks[4]. Such behaviors require the orchestration of activity across large groups of neurons, or ensembles, whose dynamics are governed by the structure of neural circuits[6]. We identified a reduction in the entropy of population activity across a large array of ensemble sizes, suggesting that the coding vocabulary of populations of neurons in the dCA1 region of hippocampus is compromised in this mouse model of amyloid pathology
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