RT Journal Article
SR Electronic
T1 Loss of <em>NF1</em> causes tactile hypersensitivity and impaired synaptic transmission in a <em>Drosophila</em> model of autism spectrum disorder
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.03.04.482984
DO 10.1101/2022.03.04.482984
A1 Dyson, Alex
A1 Garg, Shruti
A1 Evans, D. Gareth
A1 Baines, Richard A.
YR 2022
UL http://biorxiv.org/content/early/2022/03/04/2022.03.04.482984.abstract
AB Autism Spectrum Disorder (ASD) is a neurodevelopmental condition in which the mechanisms underlying its core symptomatology are largely unknown. Studying animal models of monogenic syndromes associated with ASD, such as neurofibromatosis type 1 (NF1), can offer insights into its aetiology. Here, we show that loss of function of the Drosophila NF1 ortholog results in larval tactile hypersensitivity, paralleling the sensory abnormalities observed in individuals with ASD. Mutant larvae also exhibit synaptic transmission deficits at the glutamatergic neuromuscular junction (NMJ), with increased spontaneous but reduced evoked release. Diminished expression of NF1 specifically within central cholinergic neurons induces both excessive neuronal firing and tactile hypersensitivity, suggesting the two may be linked. Furthermore, both impaired synaptic transmission and behavioural deficits are fully rescued via knockdown of Ras proteins. These findings validate NF1-/- Drosophila as a tractable model of ASD with the potential to elucidate important pathophysiological mechanisms.Competing Interest StatementThe authors have declared no competing interest.