Inhibitory representations: their formation, modulation and function in memory circuits. (360G-Wellcome-206405_Z_17_Z)

During habituation, animals learn to ignore a familiar stimulus following a period of passive exposure. Our recent work shows that Drosophila olfactory habituation arises from the potentiation of inhibitory synapses onto excitatory neurons that respond to the familar odorant. We observed that such inhibitory potentiation creates a negative image of odor-evoked excitation to reduce subsequent responses to this odorant. Because most brain systems have inhibitory motifs similar to the one analyzed here, we proposed that negative-images could underlie habituation across systems and species. The proposed research will first study how negative representations are constructed in the well-defined Drosophila olfactory microcircuit. It will then examine how these inhibitory representations and their effects are regulated. In doing so it will test the idea that reinforcement prevents habituation by blocking inhibitory plasticity, and that attention or dishabituating stimuli override habituation through neuromodulatory suppression of key inhibitory neurons. Finally, the proposed experiments will build on observations on mechanisms required for decay of predator-presence memory, to test a new hypothesis in which inhibitory representations reversibly mask learned behavior. Of fundamental importance, the work is also clinically relevant because defects in memory encoding, recall and habituation are associated with psychiatric conditions including PTSD, autism and schizophrenia.