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 had reported a predominant expression of ChT in memory processing and storing region of the Drosophila brain called mushroom bodies (MBs). It is unknown how ChT contributes to the functional principles of MB operation. Here, we demonstrate the role of ChT in Habituation, a non-associative form of learning. Odour driven habituation traces are laid down in ChT dependent manner in antennal lobes (AL), projection neurons (PNs), and MBs. We observed that reduced habituation due to knock-down of ChT in MBs 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 MBs shows characteristics similar to the major reported 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 and suggest that its dysfunction may contribute to neuropsychiatric disorders like ASD. Author summaryHabituation is a conserved phenomenon that enables an organism to enhance attention only on salient stimuli in the surroundings and ignore stimuli without any positive or negative consequences. The circuitry, regulators, and molecular mechanisms involved in habituation are poorly understood. By using Drosophila model system, we demonstrate that Choline Transporter (ChT) regulates olfactory habituation and its central operational features. We show for the first time that ChT is localised in GABAergic neurons and demonstrate that reduced levels of ChT in mushroom body and GABAergic neurons lead to defective habituation, which is correlated to augmented sensory perception. Our data provides a new perspective of ChT in habituation and provides avenues for future research to investigate the molecular correlates of ChT in habituation-associated neuropsychiatric disorders.

Automated summary

The study demonstrates the crucial role of Choline Transporter (ChT) in habituation in Drosophila, showing that it regulates habituation and incoming stimuli through interactions between excitatory and inhibitory neurons at multiple circuit loci. The lack of ChT in MBs may lead to characteristics similar to Autism spectrum disorders (ASD), suggesting a potential link between ChT dysfunction and neuropsychiatric disorders.