Keleman Group Research
Molecular and cellular basis of learning and memory in Drosophila
To survive and reproduce in ever-changing environment, animals need to be able to modulate their behaviour upon experience. We seek to understand this process of learning and memory by studying a specific form of behavioural plasticity in Drosophila at the molecular, cellular, and circuit levels.
- Figure 1 (Click to view legend)
The learning paradigm we have chosen to investigate is courtship conditioning in Drosophila. This is naturally occurring form of learning in which males learn to choose appropriate females as courtship objects. Naïve Drosophila males court both mated and virgin females, yet only virgins will be receptive to their mating attempts. Mated females actively reject courting males. Having experienced such rejection, a male is subsequently less inclined to court other mated females, but will still court virgin females as vigorously as a socially naive male (Fig.1). As with many other learning paradigms, this behavioural modification can be of either short or long duration, depending on the training regime. We aim to understand the molecular, cellular and circuit mechanisms that underlie this robust and powerful form of memory.
Molecular mechanisms of courtship memory
Despite the many molecular factors and even whole molecular pathways that have been implicated in learning and memory over last thirty years, there are clearly still many more essential molecular components of memory formation to be discovered. With the powerful new genetic tools available in Drosophila, we can now use genome-wide transgeneic RNAi to systematically test the function of every gene in Drosophila genome. We are currently conducting such a genome-wide RNAi screen to identify the genes required for courtship memory. We hope here to both discover new genes and pathways involved in courtship conditiong, and to gain further insight into those that have already been implicated in this form of learning and memory.
One phylogenetically conserved class of proteins already known to function in learning and memory are the CPEB proteins. The molecular basis for this function remains however obscure. CPEB proteins are thought to regulate RNA trafficking and/or translation, and thus might contribute to local protein synthesis in activated synapses. To test this hypothesis for the Drosophila CPEB protein Orb2, we have generated orb2attp allele (Fig.2), which allowed us to rapidly introduce any modification of the endogenous Orb2 protein in the tissue selective manner and test its role in courtship conditioning. With this system we can investigate the precise structural requirements for Orb2 function in long-term memory, examine its subcellular localization and trafficking, and identify specific RNAs or proteins that interact with Orb2.
- Figure 2 (Click to view legend)
Circuit mechanisms of courtship learning
- Figure 3 (Click to view legend)
To understand how courtship conditioning is implemented in the Drosophila brain, we also need to delineate the underlying neuronal circuit at the cellular resolution. What are the sensory cues important for this learning, how are they processed, how is this processing modulated by experience, and how does plasticity at the circuit level translate into behavioural plasticity?
We have recently uncovered a simple learning rule and identified key components of the neuronal circuit of courtship conditioning. Courtship learning reflects an enhanced behavioural response to the male pheromone cis-vaccenyl acetate (cVA), which remains on females after mating and distinguishes them from virgins. We have identified a specific class of dopaminergic neuron, aSP13 in the protocerebrum that is critical for courtship learning and provides input to the mushroom body (MB) gamma lobe (Fig.3). We postulate that, during learning, dopamine modulates the processing of cVA signals within the gamma lobe neurons, resulting in an increased sensitivity to cVA and hence an increased ability to discriminate mated females from virgins. Our ongoing efforts are aimed at identifying additional components of this circuit, and to determine how cVA signals are processed within it, with the ultimate goal of understanding how courtship conditioning is implemented in the Drosophila brain.
The long-term goal of these studies is to provide a complete picture of how the specific experience of courtship rejection modulates Drosophila male’s subsequent mating strategy. We hope that this will serve as a paradigm for more complex forms of learning and memory in the fly and other species.