Choline Transporter regulates olfactory habituation via a neuronal triad of excitatory, inhibitory and mushroom body neurons

Choline is an essential component of Acetylcholine (ACh) biosynthesis pathway which requires high-affinity Choline transporter (ChT) for its uptake into the presynaptic terminals of cholinergic neurons. Previously, we reported a predominant expression of ChT in memory processing and storing region of Drosophila brain called mushroom bodies (MB). It is unknown how ChT contributes to the functional principles of MB operation. Here, we demonstrate the role of ChT in non-associative form of learning, Habituation . Odour driven habituation traces are laid down in ChT dependent manner in antennal lobes (AL), projection neurons (PN) and MB. We observed that reduced habituation due to knockdown of ChT in MB causes hypersensitivity towards odour, suggesting that ChT also regulates incoming stimulus suppression. Importantly, we show for the first time that ChT is not unique to cholinergic neurons but is also required in inhibitory GABAergic neurons to drive habituation behaviour. Our results support a model in which ChT regulates both habituation and incoming stimuli through multiple circuit loci via an interplay between excitatory and inhibitory neurons. Strikingly, the lack of ChT in MB recapitulates major features of Autism spectrum disorders (ASD) including attenuated habituation, sensory hypersensitivity as well as defective GABAergic signalling. Our data establish the role of ChT in habituation learning and suggest that its dysfunction may contribute to neuropsychiatric disorders like ASD.