How does mitochondria affect neuron function?
Most organisms rely on the sense of smell to understand what is happening around them. Is there any food around? Are there any predators to watch out for? Any potential mates? This requires the animal to wade through the myriad odors in their environment and discern which is meaningful and which is not. How is this achieved?
One guide is the animals' previous experience with the odor. Certain smells could remind them of a food they once enjoyed, or it could remind them of a food that made them sick. These kinds of prior experience will determine how the animal will behave towards that odor.
C. elegans can also do the same: when they are exposed to some odors in the absence of food, what was once an innately attractive odor is now deemed meaningless or even repulsive (aversive learning). In contrast, if a smell was previously associated with food, the smell may become even more attractive (positive learning). With repeated training, this newly learned information can be retained for several hours or days - an odor-associated memory.
We find that mitochondria - the organelle that produces energy, the "powerhouse of the cell" - play a role in acquiring and retaining these types of memory. By taking advantage of the simple nervous system and the many genetic and molecular tools available in C. elegans, we are looking into the mechanism of how this works, with the hope that something similar could be at play in humans.
The simple, yet versatile model organism C. elegans
C. elegans are small microscopic roundworm nematodes, about ~1 mm in length. Despite its small size and simple body plan, they share many biological similarities to humans and thus provide a simple and tractable system to understand how our body works.
C. elegans has a nervous system that consists of 302 neurons. This simple nervous system can also be used to study how molecular machineries within these cells generate behavior. To assess how worms smell, we can conduct a simple choice assay in which worms are given a choice between an odor and no odor (solvent). If an attractive odorant such as 2-butanone is given one side and just the diluent in the other, worms crawl towards the source of the odor and accumulate on that side (picture below). We call this a chemotaxis assay.
A typical chemotaxis assay. Attractive odor 2-butanone was placed on the left square, diluent on the right. More worms are drawn to the right square with the odor.
Mitochondrial calcium and odor memory
Using the chemotaxis assay, we found that mutant worms for the gene mcu-1 were defective for odor learning. MCU-1 is the pore forming unit of the mitochondria calcium uniporter (MCU) and brings in calcium into the mitochondrial matrix. Long story short, we found that calcium influx into the mitochondrial matrix signals the release of a neuropeptide from the odor sensing neuron. This neuropeptide release is required for the type of odor learning that we study. Our study showed that mitochondrial activity can directly affect neuropeptide secretion at the synapse.
We are currently trying to find if this type of neuropeptide control happens in other neurons, and how certain neuropeptides are selectively regulated through this mechanism.