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Introduction of tau oligomers into cortical neurons alters action potential dynamics and disrupts synaptic transmission and plasticity
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Hill, Emily, Karikaria, Thomas K., Moffat, Kevin G., Richardson, Magnus J. E. and Wall, Mark J. (2019) Introduction of tau oligomers into cortical neurons alters action potential dynamics and disrupts synaptic transmission and plasticity. eNeuro, 6 (5). 0166. doi:10.1523/ENEURO.0166-19.2019 ISSN 2373-2822.
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Official URL: https://doi.org/10.1523/ENEURO.0166-19.2019
Abstract
Tau is a highly soluble microtubule-associated protein that acts within neurons to modify microtubule stability. However, abnormally phosphorylated tau dissociates from microtubules to form oligomers and fibrils which associate in the somatodendritic compartment. Although tau can form neurofibrillary tangles (NFTs), it is the soluble oligomers that appear to be the toxic species. There is, however, relatively little quantitative information on the concentration-dependent and time-dependent actions of soluble tau oligomers (oTau) on the electrophysiological and synaptic properties of neurons. Here, whole-cell patch clamp recording was used to introduce known concentrations of oligomeric full-length tau-441 into mouse hippocampal CA1 pyramidal and neocortical Layer V thick-tufted pyramidal cells. oTau increased input resistance, reduced action potential amplitude and slowed action potential rise and decay kinetics. oTau injected into presynaptic neurons induced the run-down of unitary EPSPs which was associated with increased short-term depression. In contrast, introduction of oTau into postsynaptic neurons had no effect on basal synaptic transmission, but markedly impaired the induction of long-term potentiation (LTP). Consistent with its effects on synaptic transmission and plasticity, oTau puncta could be observed in the soma, axon and in the distal dendrites of injected neurons.
| Item Type: | Journal Article | ||||||
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| Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||||
| Journal or Publication Title: | eNeuro | ||||||
| Publisher: | Society for Neuroscience | ||||||
| ISSN: | 2373-2822 | ||||||
| Official Date: | 25 September 2019 | ||||||
| Dates: |
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| Volume: | 6 | ||||||
| Number: | 5 | ||||||
| Page Range: | 0166 | ||||||
| DOI: | 10.1523/ENEURO.0166-19.2019 | ||||||
| Status: | Peer Reviewed | ||||||
| Publication Status: | Published | ||||||
| Access rights to Published version: | Open Access (Creative Commons) | ||||||
| Date of first compliant deposit: | 17 September 2019 | ||||||
| Date of first compliant Open Access: | 18 October 2019 | ||||||
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