My lab studies the brains of larval fruit flies as models of neural computation. We are interested in the rules by which the larval brain transforms sensory input into motor output to navigate an uncertain environment, how the larva’s brain changes these rules as it learns new information, and how these rules and changes are encoded in the activities and connections of individual neurons. In this talk, I will try to tell two stories, one (published) about learning and memory formation and one (unpublished) about recording neural activity in freely moving larvae.

Learning and memory: Fruit fly larvae can learn to associate odors with reward or punishment and change their behaviors accordingly. I have often compared teaching larvae to teaching undergraduates (NOT at NYU or Princeton, of course):  it requires a lot of effort to teach them anything, only about 60% get it, and none of them remember when you test them the next day. This turns out to have slandered the larvae. I’ll describe a new device we constructed that more accurately measures individual animals’ preferences for odor along with an in situ optogenetic training protocol that can be precisely timed and titrated. Using this device, we show that all larvae learn given enough training, that learning is a sudden all-or-none switch from an unlearned to learned state, and we demonstrate formation of stable long-term memories.

Two photon two color video rate volumetric microscopy in freely crawling larvae: A major advantage of the larva as a research model is that due to its translucent cuticle, it is possible to use optical microscopy in intact but immobilized larvae to record the activities of neurons labeled with genetically encoded calcium indicators.  To really understand how the brain encodes and controls behavior, we need to make similar recordings in freely crawling (not immobilized) larvae. The nematode C. elegans also has a transparent cuticle, and talented labs have developed fluorescence microscopy techniques to record from every neuron in a freely crawling nematode. You might think the same techniques could be used on larvae, but in fact, it’s been very challenging to overcome the unique motion artifacts associated with the larva’s body plan and pattern of motion. I will describe a two photon tracking microscope that can make two color recordings from freely crawling larvae and our progress in overcoming various artifacts associated with the motion.