Nervous system function and behavior in C. elegans embryos

Abstract

Events in early brain development are known to have profound impacts on later- life developmental outcomes. Most studies of circuit function and behavior use post- natal samples, likely due to the inaccessibility of intact embryos. How does nervous system function emerge and begin to control behavior during embryonic development? The optically accessible C. elegans embryo provides a powerful tool with which to address this question. GABA signaling is proposed to play important roles in circuit formation and plasticity, making GABA an interesting molecule to study in the context of embryonic nervous system function. We find that GABA release from developing motor neurons occurs prior to localization of pre- and post-synaptic ion channels in the nerve ring. Synaptic vesicle release contributes to but is not required for early motor neuron GABA release. Although bestrophin channels are known to mediate non-synaptic GABA release from glia, we find that bestrophins act in neurons to promote synaptic GABA release. These results indicate a role for non-synaptic GABA transmission in prenatal circuits. Previous work described a sleep-like behavior in late embryonic development. We took two approaches to identify developmental and circuit mechanisms underlying late embryonic behavior. First, we screened genes associated with autism spectrum disorder (ASD), which is theorized to have roots in early neurodevelopment. Several ASD risk genes regulate embryonic sleep-like behavior. An allele of CaV1 (with an equivalent amino acid change to a Timothy Syndrome allele) alters embryonic behavior by its effects downstream of the sleep active neuron RIS. Additionally, genes required for sensory neuron function are required for wild type behavior, suggesting sensory neurons regulate circuit function before the presence of externally generated sensory cues. These results define elements underlying embryonic neural circuit function.