The roles of muscarinic receptors in drosophila olfaction

G-protein-coupled receptors (GPCRs) have ubiquitous roles in transducing extracellular signals into cellular responses. Unexpectedly, it was found that GPCRs are voltage dependent. However, whether GPCRs’ voltage dependence plays a physiological role and affects behavior was not yet investigated. To try and answer this question manipulation of the GPCRs’ voltage sensor is required. At the moment the metabotropic muscarinic acetylcholine receptors (mAChRs) are the most suitable as they are the only GPCRs for which their voltage sensor domain is known. Fruit flies serve as a good model system to study the role of mAChRs voltage dependence, due to the low number of mAChRs variants and simple nervous system that is highly amenable to genetic manipulation. However, a prerequisite to conducting such research is knowledge on the behavioral roles of Drosophila mAChRs and whether they are also voltage dependent. Surprisingly, despite the abundance of mAChRs in the Drosophila brain, very little is known about mAChRs physiological functions and properties. Here we show that Drosophila mAChRs are voltage dependent and that aversive olfactory conditioning in adult flies requires dendritic mAChRs in the gamma neurons of the mushroom body. In addition, mAChRs expressed in a subpopulation of GABAergic local neurons (iLNs) in the antennal lobe (AL) have a dual role: they directly excite iLNs and they are required for short-term potentiation allowing iLNs to cope with the strong short-term depression of their synaptic input. This iLN plasticity shapes AL output and affects behavior.