Geon The Role of Microtubules
and Tau Proteins in Neuronal Excitability



For more than three decades, the evidence (Matsumoto and Sakai, 1979) that microtubules might play a role in neuronal excitability has been largely ignored. This situation was changed a few years ago, when several groups provided direct evidence for the involvement of microtubule-associated protein Tau in excitability. Since then, further evidence continues to accumulate. The microtubule-depolymerizing agent nocodazole has been demonstrated to reduce burst activity and seizure severity. Very recently, Hatch et al. (2017) showed that the hyperphosphorylated Tau could reduce excitability by modulating the axon initial segment (AIS) in a microtubule-dependent manner. These findings support the Microtubule Model for Excitability (MTME) proposed in Paper 1. This paper will employ MTME to explain:

  1. How elevated 4-repeat Tau may cause hyperexcitability.
  2. How microtubule depolymerization can reduce excitability.

The latter may play a key role in seizure termination, as intensive neural activities often lead to Ca2+ overload, which is known to cause microtubule depolymerization.


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(2017-9-1). Click on the above links to access the most recent version. Click her to download the PDF file of the original version posted on February 13, 2017.