Abstract

Many neurons do not fire action potentials, meaning that electrical activity is spatially localised in the neuron: synaptic inputs lead directly to transmitter release locally where the inputs arrive, not in other parts of the neuron. Why? Few examples exist where this neuronal compartmentalisation has a clear behavioural function. We propose a novel hypothesis to link compartmentalisation to behaviour: that in the Drosophila brain, compartmentalised activity in an inhibitory interneuron, ‘APL’, allows localised synaptic modifications to oppose memory formation. Learning modifies (usually weakens) synapses between odour-responsive Kenyon cells (KCs) and behaviour-controlling mushroom body output neurons (MBONs). MBONs that control opposing behaviours (approach vs. avoid the odour) occupy segregated ‘MBON zones’ along KC axons. Together with these segregated ‘MBON zones’, the fact that APL provides local feedback inhibition to KCs could explain why APL suppresses learning. APL would suppress learning if APL locally inhibits MBONs (via KCs) and KC->APL plasticity in each ‘MBON zone’ mirrors KC->MBON plasticity in that zone. The latter means that learning causes both APL odour responses and APL’s inhibitory output strength in each zone to change in the same direction as MBON odour responses in that zone (but not other zones). Because APL inhibits KCs, this KC->APL plasticity would oppose KC->MBON plasticity, and if this opposition is local to each zone, it would lessen the learning-induced imbalance in MBON activity that underlies olfactory memory. (This logic is explained in more detail in the main summary.) We will test these predictions using two-photon volume imaging of APL and MBONs, using genetically encoded calcium indicators. We will record neural activity while presenting odours to the fly, and/or locally activating or inhibiting APL or dopaminergic neurons by ectopically expressing receptors for chemicals that we locally apply to specific MBON zones.