Abstract
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.
Highlights
Acetylcholine (ACh) is the fundamental neurotransmitter of cholinergic neurons
By using Drosophila model system, we demonstrate that Choline Transporter (ChT) regulates olfactory habituation and its central operational features
In view of our previous findings that report high expression of Choline transporter (ChT) in mushroom bodies (MBs), we study a putative role of ChT in ‘Habituation’ which is widely regarded as a prerequisite for more complex form of associative learning
Summary
Acetylcholine (ACh) is the fundamental neurotransmitter of cholinergic neurons These neurons are widely distributed throughout the central nervous system (CNS) in the vertebrate and invertebrate brain. Given the widespread distribution of cholinergic neurons in the vertebrate and invertebrate brain, ACh mediated neurotransmission is crucial for neural functions that include varied sensory modalities. Drosophila MBs express ChAT and VAChT and require ACh for its function [6,7]. We recently reported a preponderance of ChT in Drosophila MBs as compared to ChAT and VAChT [8]. Habituation to repetitive footshock stimuli requires intact MBs [14] These reports signify the importance of MB function in habituation behaviour
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