Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

We have shown that over-expression of human tau (0N3R) in Drosophila larval motor neurons causes significant morphological and functional disruption to the neuromuscular junctions (NMJs). Tau-expressing NMJs are reduced in size with irregular and abnormal bouton structure. Immunocytochemical analysis shows that the abnormal NMJs still retain synaptotagmin expression and form active zones. Functionally, the NMJs exhibit abnormal endo/exocytosis as revealed by incorporation of the styryl dye FM1-43. Electrophysiological studies showed that with low frequency stimulation (1 Hz), evoked synaptic potentials produced from tau over-expressing motor neurons were indistinguishable from wild type, however, following high frequency stimulation (50 Hz), evoked synaptic potentials were significantly decreased. Analysis of the number and distribution of mitochondria showed that motor neurons over-expressing tau had a significant reduction in functional mitochondria in the presynaptic terminal. Collapsing the mitochondrial membrane potential in wild type larvae phenocopied the effects of tau over-expression on synaptic transmission. Our results demonstrate that tau over-expression in vivo cause a synaptic dysfunction, which may be caused by a reduced complement of functional mitochondria.

Original publication

DOI

10.1016/j.nbd.2005.05.029

Type

Journal article

Journal

Neurobiol Dis

Publication Date

12/2005

Volume

20

Pages

918 - 928

Keywords

Animals, Animals, Genetically Modified, Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone, Cell Respiration, Disease Models, Animal, Drosophila, Electric Stimulation, Excitatory Postsynaptic Potentials, Exocytosis, Green Fluorescent Proteins, Humans, Larva, Mitochondria, Motor Neurons, Mutation, Neuromuscular Junction, Neuromuscular Junction Diseases, Presynaptic Terminals, Synaptic Transmission, Synaptotagmin I, Tauopathies, tau Proteins