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 (MT) model proposed in Paper 1. This paper will extend the MT model to explain (1) how excessive 4-repeat Tau may cause hyperexcitability, and (2) how seizures can be terminated by the detyrosinated tubulins which are disassembled from microtubules at AIS.


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