Studying axonal transport and neuronal function using NLO and superresolution microscopy

Neurons critically rely on active transport of mitochondria to match energy production and Ca2+ buffering to local demand. Their complex morphology renders them extremely sensitive even to  subtle defects in axonal transport. Consequently, defective mitochondrial trafficking is involved in a number of neurological and neurodegenerative diseases. In this project we aim to advance our fundamental understanding of this transport using state of the art nonlinear, super-resolution and fluorescence live cell imaging microscopy in primary hippocampal neurons. First, we will characterise the interplay between activity-related Ca2+ signalling and axonal mitochondrial transport. These results will clarify the supportive role of this regulatory mechanism during network activity. Secondly, we aim to unveil a novel regulatory mechanism shaping mitochondrial transport, based on the modulation of microtubuletrack dynamics. Finally, in light of recent findings, we will investigate the bold but promising hypothesis that general anesthetics interfere with the mitochondrial transport system and are therefore valuable tools to study its regulation. These results will expand our understanding of mitochondrial transport regulation, as well as provide novel insight into the (on or off-target) effects of anesthetics, which remain poorly understood despite their widespread use and tremendous clinical importance.