Andrea Edwards-Cintrón, Kristi Zoga & Michael P. Hart

University of Puerto Rico, Río Piedras Campus

Department of Genetics, Perelman School of Medicine, University of Pennsylvan


Autism spectrum is a heterogeneous set of developmental conditions characterized by changes in

behavior, including altered social skills, communication, and restricted and repetitive behaviors.

Genetic studies have identified hundreds of genes, collectively known as autism-associated genes,

that may contribute to understanding the molecular basis of Autism. It is hypothesized that Autism

may result from an imbalance between inhibitory and excitatory signaling within the brain.

Therefore, it may be beneficial to study roles for autism genes in these signaling pathways. We

hypothesize that synaptic autism-associated genes may disrupt excitatory/inhibitory balance

through roles in GABAergic inhibitory plasticity. We used Caenorhabditis elegans to screen

conserved autism genes for roles in the behavioral and morphological plasticity of the GABAergic

inhibitory neuron DVB. Recessive loss of function mutations in each gene were crossed with a

fluorescent transgene that allows visualization of the DVB neuron. The genes examined were the

following: CACNA2D3/unc-36, CACNA1E/unc-2, ANK2/unc-44, and SETD5/set-9. Day 1 and day 3

adult male C. elegans for each mutant were subjected to aldicarb assays and confocal microscopy

to quantify DVB-dependent behavior (spicule protraction) and neuron morphology. Our preliminary

data supports the hypothesis that autism genes can impact spicule protraction behavior and DVB

neuron morphology, thus playing roles in inhibitory plasticity and signaling. By screening autism

genes for roles in inhibitory plasticity, this study will lend evidence to the excitatory/inhibitory

balance hypothesis and determine molecular mechanisms by which autism-associated genes

impact behavior.

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