RT Journal Article
SR Electronic
T1 Introduction of Tau Oligomers into Cortical Neurons Alters Action Potential Dynamics and Disrupts Synaptic Transmission and Plasticity
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0166-19.2019
DO 10.1523/ENEURO.0166-19.2019
VO 6
IS 5
A1 Emily Hill
A1 Thomas K. Karikari
A1 Kevin G. Moffat
A1 Magnus J. E. Richardson
A1 Mark J. Wall
YR 2019
UL http://www.eneuro.org/content/6/5/ENEURO.0166-19.2019.abstract
AB 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.