Circuit mechanisms of courtship conditioning in Drosophila

Almost all innate behaviors are plastic to some extent, being modified by experience as the individual learns by interacting with its environment. A key mechanism thought to be responsible for such behavioural adaptation is synaptic plasticity. While the molecular mechanisms of synaptic plasticity are becoming increasingly well understood, the mechanisms that operate at the neuronal circuit level to achieve behavioural plasticity remain unclear. Drosophila is an ideal model system to explore behavioural plasticity at the circuit level, as it offers a powerful set of genetic tools, a relatively simple brain and a rich repertoire of complex and plastic behaviours. One particularly robust form of behavioural plasticity in Drosophila is the ability of males to learn to selectively court virgin rather than mated females. Our current data suggest that Drosophila males use a very simple learning rule to optimize their mating strategy: naive males are promiscuous and court both mated females and virgins, but through the experience of rejection they become more sensitive to the inhibitory effect of the male-derived pheromone cVA, which allows them to discriminate mated females from virgins. We propose that learning is mediated by a dopamine signal conveyed from aSP13 neurons to mushroom body gamma neurons. It is however unknown how this putative dopamine learning signal is generated and used to "write" this specific memory, and how this memory is subsequently "read" to ensure preferential courtship of virgins. This proposal will address these questions through the identification and functional characterization of the missing input and output elements of this learning circuit. Using a rich variety of existing and newly-developed genetic tools, together with sophisticated combinatorial and intersectional strategies, we will identify, visualize and manipulate the specific neurons involved in courtship conditioning. Specifically, we will define the olfactory inputs that convey the cVA signal to the mushroom bodies, identify and characterize the inputs that aSP13 uses to generate it`s learning signal, and identify and characterize mushroom body output neurons that we anticipate will feed into the courtship circuitry so that past experience can guide present courtship. We believe that these approaches will lead to detailed understanding of how Drosophila male learns to discriminate mated females from virgins, and in doing so provide more general insights into how plasticity within defined neural circuits allows animals to adjust their innate behaviours to best suit the local environment.

Our goal is to identify and understand circuit mechanisms underlying learning and memory. As a model system we have chosen to study a naturally occuring form of learning where Drosophila male learns to discriminate between two types of females: virgin females that are generally receptive and recently mated females which generally reject them. Males after being rejected are less inclined to court subsequent mated females although they remain enthusiastic towards virgin females. Recently we have provided important foundation how this form of learning might be implemented in male brain. We identified a specific class of dopaminergic neurons (aSP13), that are both required and sufficient for this type of learning. They innervate the mushroom body gamma lobe (MB), a neuropil known to be necessary for memory formation in Drosophila.Since, it is thought that memories are stored in the synapses between the MB and the MB output neurons we have sought to identify the relevant output neurons to test this hypothesis. To identify the specific MB output neuron we searched the Vienna enhancer-Gal4 collection for the neurons with the dendritic arbor in the MB neurons. We identified a specific class of M6 neurons, which arborize in the tip of the MB lobe and whose activity is required downstream of the MB neurons during courtship memory retrieval, which is consistent with its function as an output neuron.Moreover, we have investigated the physiological basis of this behavioral phenomenon using optogenetics and we have determined that dopamine, which is likely provided by the dopaminergic aSP13 neurons, gates the output of the MB onto the M6 output neurons and thus the synapses between the MB and M6 output neurons are likely a site of synaptic plasticity responsible for this behavioral modification such as selective courtship suppression towards mated females after prior rejection by this type of females.