Gerald Rubin, PhD
Vice President, Howard Hughes Medical Institute, and
Executive Director, Janelia Research Campus
(November 8, 2016)

Learning and Memory in Drosophila

Learning and memory can be studied at many different levels, from human behaviors, down to neurons in a dish. To understand how memories are formed at the level of cells and circuits, a model organism, like the fruit fly, can be used. In order to understand how circuits change with learning, a detailed map of the fly brain is required. Dr. Rubin discussed his work on learning and memory using the fly olfactory system. His work has shown that individual parts of a memory, or engrams, are stored in multiple sub-circuits, which can be combined to guide behavior. These sub-circuits have different mechanisms for creating and changing memory. Future work, Dr. Rubin says, will examine whether this data will help in the understanding of how the brain uses memory to guide behavior.

To probe the workings of the nervous system, we will need detailed anatomical information and the ability to assay and manipulate the function of individual neuronal cells and cell types. The intellectual framework for such an approach has been articulated by several research groups over the past 10 years. But tools have been inadequate for the job. In my lecture, I discussed efforts to develop and apply some of the tools that will be required for a comprehensive analysis of the anatomy and function of the small brain of Drosophila melanogaster at the level of individual cell types and circuits using examples from our recent work on the mechanisms of learning and memory.

Experiments aimed at uncovering the mechanisms by which different forms of memory are established and maintained, and then coherently coordinated to drive behavior, are facilitated by using a model system in which the relevant cells and circuits can be identified and manipulated either individually, or in specific combinations. In my lecture, I described experiments performed in such a model system, the Drosophila olfactory circuit.

Animals use memories of past events to predict the future. In some cases, an animal is best served by making a prediction based solely on their most recent experience. In others, a series of experiences is integrated to make a probabilistic prediction, discounting an event experienced only once. How are such different strategies implemented in the brain? Our results suggest that individual components of a memory — often called engrams — are simultaneously stored in distinct sub-circuits whose outputs can then be combined upon recall to affect behavior. These sub-circuits vary in their rules for writing, updating and retaining these engrams, having differences in synaptic plasticity and circuit properties.

Will these data, combined with theory and modeling, be sufficient to understand how a brain executes complex computations to achieve sophisticated behaviors? Time will tell.