UC San Diego

Regulated neural circuit activity is essential for cognitive ability and behavioral activities whereas aberrant circuit function is a hallmark of disorders, including Autism Spectrum Disorders and epilepsy. However, the specific mechanisms of regulating neural circuit remain obscure. This study uses a unique C. elegans model of circuit hyperactivity, a gain-of-function mutation in a nicotinic acetylcholine receptor subunit, acr-2(gf). The acr-2(gf) gene product functions in acetylcholine motor neurons and results in a disrupted neural circuit by hyperactivating the acetylcholine excitatory motor neurons and causing impaired locomotion with stochastic muscle convulsions. From previous genetic screening, a functional linkage has been found between neuronal activity and one missense mutation within conserved translation initiation factor eif-3.g, allowing suppression on acr-2(gf) convulsion. The aim of my master thesis is to identify genes affecting motor neural circuit function through eif-3.g and acr-2(gf). Specifically, I am involved in analyzing mutations isolated from a genetic suppressor screen for genes that restored convulsion rate in eif-3.g(ju807); acr-2(gf) animals. I identified one eif-3.g suppressor as protein translation repressor lin-66, which encodes for heterochronic gene downregulating development. We speculate that gene lin-66 gene is one of the targets of or participate in eif-3.g function in motor neurons. Our studies provide fundamental mechanism for future implication on understanding the regulation between motor neurons and translational initiation factors.