Flies can be taught to associate odours with punishing shock, heat or bitter-taste, or rewarding sugars or water. After training they either avoid an odour predicting unpleasantness or approach an odour expecting reward. The Drosophila brain has approximately 100,000 neurons and recent progress suggests that the fly mushroom body, an ensemble of around 2200 intrinsic Kenyon cells (KCs), might be part of a circuit upon which the traditional cellular, systems and behavioural neuroscience boundaries can be bridged. Genetic and technical advances provide the means to specifically and reproducibly manipulate or monitor the function and activity of defined sets of fly neurons with temporal resolution. Furthermore, it is now appreciated that the fan-out fan-in neural architecture of the mushroom body shares structural features and perhaps a coding logic with that of the cephalopod vertical lobe and the mammalian olfactory, cerebellar and hippocampal structures. Studying the reduced complexity of the mushroom body should therefore be generally informative.
During olfactory learning in fruit flies dopaminergic neurons assign value to odour representations in the mushroom body KCs. We recently identified a set of downstream glutamatergic mushroom body output neurons (MBONs) whose dendritic fields overlap with dopaminergic neuron projections in the tips of the mushroom body horizontal lobes. This anatomy and their odour-tuning suggests that these neurons pool odour-driven KC synaptic outputs. Like that of KCs, output from these MBONs is required for expression of appetitive and aversive memory performance. Moreover, appetitive and aversive olfactory conditioning bi-directionally alters the relative odour-drive of these MBONs. Direct block of these MBONs in naïve flies mimics appetitive conditioning, being sufficient to convert odour-driven avoidance into approach, while optogenetically activating these neurons induces avoidance behaviour. Therefore, drive to these neurons reflects odour-directed behavioural choice. We integrate this model with further MBON pathways. During learning reinforcing dopaminergic neurons skew the mushroom body network by driving zonally restricted plasticity at synaptic junctions between the KCs and subsets of the overall small collection of MBONs (~34). Reactivation of this skewed KC-MBON network retrieves memory of odour valence and guides appropriate approach or avoidance behaviour.