Internal representation of the reinforcement system
Final Report Abstract
The formation of associative memory requires the internal integration of two sensory stimuli, and the site of such convergence in Drosophila olfactory learning is the mushroom body (MB). Intriguingly, the MB is known to be important for both appetitive and aversive memories. In this Emmy-Noether Programme, I addressed the following aims: (1) Addressing how the aversive and appetitive reinforcing systems respectively generates distinct qualities of odour memories and subsequent behavioural changes; (2) Elucidating the anatomy and the function of neural circuits with special emphasis on different reinforcing systems; (3) Identifying the cellular and molecular mechanisms of olfactory learning by genetically manipulating the cAMP / PKA pathway and its potential target, Synapsin. The formation of associative memory requires the internal integration of two sensory stimuli. In Drosophila, the type I adenylate cyclase encoded by the rutabaga gene serves as a molecular coincidence detector for odor and sugar/shock. Accordingly, rutabaga mutant flies have a defect in odor memory. We have found that limiting wild-type cyclase expression to the firstorder olfactory interneurons selectively restores appetitive, but not aversive, odor memory. In contrast, expression in the brain structure mushroom body (MB) restored both memory types of the rutabaga mutant. Thus, appetitive learning may induce multiple memory traces in both first- and second-order olfactory interneurons. Furthermore, in a separate series of studies, we have identified two different presynaptic proteins, Synapsin and Bruchpilot, which are required for labile and stable forms of aversive memory, respectively. As these proteins maintain the different pools of synaptic vesicles, distinct modes of vesicle release in the MB may underlie the retrieval of labile and stable memories. To tackle functional neural circuits of the MB, I took a strategy to first identify anatomical connections and then to manipulate the function of each individual connection. We identified dozens of GAL4 enhancer trap lines labelling MB-extrinsic neurons and analyzed new connections of the MB. Given sparse availability of cellular descriptions of individual reinforcement neurons, we furthermore created a map of neuronal network by single octopaminergic neurons. To address the function of these MB extrinsic neurons in processing of reward and punishment, we conducted a screen by activating or suppressing selective extrinsic pathways using the GAL4 drivers characterized above. This revealed that small subsets of dopamine neurons projecting to the MB – three MB-M3 neurons a single MB-MP1 neuron and a single MB-MV1 neuron– are necessary and sufficient for the specific components of aversive olfactory memory. These results highlight the importance of local dopamine circuits in the MB.
Publications
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Multiple memory traces for olfactory reward learning in Drosophila. J Neurosci 2007;27:11132-8
Thum AS, Jenett A, Ito K, Heisenberg M, Tanimoto H
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Neuronal assemblies of the Drosophila mushroom body. J Comp Neurol 2008;508:711-55
Tanaka NK, Tanimoto H, Ito K
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A map of octopaminergic neurons in the Drosophila brain. J Comp Neurol 2009;513:643-67
Busch S, Selcho M, Ito K, Tanimoto H
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The mushroom body of adult Drosophila characterized by GAL4 drivers. J Neurogenet 2009;23:156-72
Aso Y, Grubel K, Busch S, Friedrich AB, Siwanowicz I, Tanimoto H
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Specific dopaminergic neurons for the formation of labile aversive memory. Curr Biol 2010;20:1445-1451
Aso Y, Siwanowicz I, Bräcker L, Ito K, Kitamoto T, Tanimoto H
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Synapsin is selectively required for anesthesia-sensitive memory. Learn Memory 2010;17:76-9
Knapek S, Gerber B, Tanimoto H
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Bruchpilot, a synaptic active zone protein for anesthesiaresistant memory. J Neurosci 2011; 31: 3453-3458
Knapek S, Sigrist SJ, Tanimoto H
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Mushroom body efferent neurons responsible for aversive olfactory memory retrieval in Drosophila. Nat Neurosci 2011;14:903- 10
Séjourné J, Plaçais PY, Aso Y, Siwanowicz I, Trannoy S, Thoma V, Tedjakumala SR, Rubin GM, Tchénio P, Ito K, Isabel G, Tanimoto H, Préat T
