Candidate Autism Genes Nrx1 and Nlg3 Lead To Ectopic Synapses in Nociceptive Neurons in Drosophila Larvae
Authors: Claudia Gualtieri; Fernando Vonhoff
Affiliation: University of Maryland Baltimore County
Keywords: e. neuronal morphogenesis; c. models of ASD
Synaptic refinement is a neuroplasticity process leading to the withdrawal of ectopic synapses formed during the initial phases of neuronal development. Extensive research has shown evidence of synaptic refinement occurring in both the central nervous system (CNS) and peripheral nervous system (PNS). However, the molecular mechanisms underlying synaptic refinement remain incompletely understood. The process of synapse elimination is crucial during development in multiple organisms as it has also been linked to the onset of neurodevelopmental disorders like autism. Evidence from postmortem studies of autistic patients that have mutations in genes associated with autism, show increased synaptic density and longer dendritic spines, suggesting a possible defect in the elimination process. The goal of this study was to determine the anatomical effects of candidate autism genes in vivo using the Drosophila model. Starting from the hypothesis that candidate autism genes would lead to the presence of ectopic synapses that branch off stereotypic connectivity patterns, anatomical synaptic innervations of cIV nociceptive sensory neurons were assessed during larval development. The candidate autism genes nrx-1 or nlg-3, respectively coding for the scaffolding proteins neurexin-1 and neuroligin-3, were downregulated using RNAi constructs. Anatomical defects were assessed by counting the number of ectopic synapses and by measuring the fluorescent area covered by synapses. Preliminary data on the anatomical effects of the downregulation of the candidate autism gene nrx-1 shows increased number of ectopic synapses in the ladder structure formed in the CNS by the axonal projection of nociceptive neurons. These findings offer the basis for investigating the processes leading to the failure in the elimination of ectopic synapses providing insights into the molecular mechanisms regulating synaptic refinement