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Open Access 01-12-2014 | Research

Tau pathology does not affect experience-driven single-neuron and network-wide Arc/Arg3.1 responses

Authors: Nikita Rudinskiy, Jonathan M Hawkes, Susanne Wegmann, Kishore V Kuchibhotla, Alona Muzikansky, Rebecca A Betensky, Tara L Spires-Jones, Bradley T Hyman

Published in: Acta Neuropathologica Communications | Issue 1/2014

Abstract

Intraneuronal neurofibrillary tangles (NFTs) – a characteristic pathological feature of Alzheimer’s and several other neurodegenerative diseases – are considered a major target for drug development. Tangle load correlates well with the severity of cognitive symptoms and mouse models of tauopathy are behaviorally impaired. However, there is little evidence that NFTs directly impact physiological properties of host neurons. Here we used a transgenic mouse model of tauopathy to study how advanced tau pathology in different brain regions affects activity-driven expression of immediate-early gene Arc required for experience-dependent consolidation of long-term memories. We demonstrate in vivo that visual cortex neurons with tangles are as likely to express comparable amounts of Arc in response to structured visual stimulation as their neighbors without tangles. Probability of experience-dependent Arc response was not affected by tau tangles in both visual cortex and hippocampal pyramidal neurons as determined postmortem. Moreover, whole brain analysis showed that network-wide activity-driven Arc expression was not affected by tau pathology in any of the brain regions, including brain areas with the highest tangle load. Our findings suggest that intraneuronal NFTs do not affect signaling cascades leading to experience-dependent gene expression required for long-term synaptic plasticity.

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Title: Tau pathology does not affect experience-driven single-neuron and network-wide Arc/Arg3.1 responses
Authors: Nikita Rudinskiy
Jonathan M Hawkes
Susanne Wegmann
Kishore V Kuchibhotla
Alona Muzikansky
Rebecca A Betensky
Tara L Spires-Jones
Bradley T Hyman
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: Acta Neuropathologica Communications / Issue 1/2014
Electronic ISSN: 2051-5960
DOI: https://doi.org/10.1186/2051-5960-2-63

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Tau pathology does not affect experience-driven single-neuron and network-wide Arc/Arg3.1 responses

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