Learning and memory deficits upon TAU accumulation in Drosophila mushroom body neurons.

Mutations in the neuronal-specific microtubule-binding protein TAU are associated with several dementias and neurodegenerative diseases. However, the effects of elevated TAU accumulation on behavioral plasticity are unknown. We report that directed expression of wild-type vertebrate and Drosophila TAU in adult mushroom body neurons, centers for olfactory learning and memory in Drosophila, strongly compromised associative olfactory learning and memory, but olfactory conditioning-relevant osmotactic and mechanosensory responses remained intact. In addition, TAU accumulation in mushroom body neurons did not result in detectable neurodegeneration or premature death. Therefore, TAU-mediated structural or functional perturbation of the microtubular cytoskeleton in mushroom body neurons is likely causal of the behavioral deficit. These results indicate that behavioral plasticity decrements may be the earliest detectable manifestations of tauopathies.