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Title: Neural circuit mechanisms of memory coding in the Drosophila mushroom body
Author: Barnstedt, Oliver
ISNI:       0000 0004 6494 4326
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2017
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Learning allows animals to adapt their behaviour to changes in the environment. In humans and other mammals, memories are stored in the hippocampus and cerebellum, whereas in insects, they are stored inside the mushroom bodies (MB). Here, MB-intrinsic Kenyon cells (KCs) form plastic synapses to MB output neurons (MBONs) that are modulated by the reinforcing action of dopaminergic neurons (DANs). Despite decades of research on the MB, the main neurotransmitter underlying the plastic KC → MBON synapse has remained a mystery. Here, I show that this synapse is cholinergic in the fruit fly Drosophila melanogaster. MBONs show fast excitatory responses to direct acetylcholine (ACh) application. KCs synthesise ACh-related proteins ChAT and VAChT. MBONs express and require nicotinic ACh receptors (nAChRs) to become fully activated by odour presentation. Lastly, artificial activation of KCs leads to MBON calcium responses that are blocked by nicotinic antagonists and genetic reduction of VAChT in KCs. Short neuropeptide F (sNPF) may play a role as a modulatory co-transmitter that can either excite or inhibit specific MBONs and DANs. The retrieval of memories is state-dependent and known to potentially change the original memory. Fruit flies need to be hungry to express appetitive memories. Hunger state depends on insulin signalling that activates the GABAergic MBON MVP2, while appetitive memory retrieval depends on decreased activity in M4/6 MBONs. Here, I show that optogenetic MVP2 activation acutely inhibits M4/6 odour responses, rendering MVP2 an inhibitory MBON interneuron. I also show that other MBONs are functionally connected to DANs, thus linking memory reinforcement and retrieval pathways in a way that enables the updating of the original memory. These findings show that associative memories in Drosophila are initially formed at cholinergic-MBON synapses, and can be retrieved and modified through an intricate KC-MBON-DAN network.
Supervisor: Waddell, Scott Sponsor: Medical Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Neurosciences ; memory ; mushroom body ; plasticity ; Drosophila ; extinction ; reconsolidation ; learning ; acetylcholine ; sNPF