Gamma Neurons Mediate Dopaminergic Input during Aversive Olfactory Memory Formation in Drosophila

Mushroom body (MB)-dependent olfactory learning in Drosophila provides a powerful model to investigate memory mechanisms. MBs integrate olfactory conditioned stimulus (CS) inputs with neuromodulatory reinforcement (unconditioned stimuli, US) [1, 2], which for aversive learning is thought to rely on dopaminergic (DA) signaling [3-6] to DopR, a D1-like dopamine receptor expressed in MBs [7, 8]. A wealth of evidence suggests the conclusion that parallel and independent signaling occurs downstream of DopR within two MB neuron cell types, with each supporting half of memory performance. For instance, expression of the Rutabaga (Rut) adenylyl cyclase in gamma neurons is sufficient to restore normal learning to rut mutants [9], whereas expression of Neurofibromatosis 1 (NF1) in alpha/beta neurons is sufficient to rescue NF1 mutants [10, 11]. DopR mutations are the only case where memory performance is fully eliminated [7], consistent with the hypothesis that DopR receives the US inputs for both gamma and alpha/beta lobe traces. We demonstrate, however, that DopR expression in gamma neurons is sufficient to fully support short- and long-term memory. We argue that DA-mediated CS-US association is formed in gamma neurons followed by communication between gamma and alpha/beta neurons to drive consolidation.