Retrograde synaptic signaling by Neurexin and Neuroligin in C. elegans

Joshua Kaplan, Ph.D.
Massachusetts General Hospital

Genetic studies have identified a large number of genes that are potentially involved in autism spectrum disorders. In particular, mutations in the proteins neurexin and neuroligin have been found in individuals with autism, as well as in those with other psychiatric disorders such as schizophrenia. Neurexin and neuroligin are found at the synaptic connections between cells in the brain, yet it remains unclear how these proteins alter the development and function of the brain.

An important goal for the field is establishing an efficient means to assess the functional importance of candidate genes identified in human genetic studies of autism. Joshua Kaplan and his collaborators at Massachusetts General Hospital are using a simple model organism, the worm Caenorhabditis elegans, as a genetic platform to assay the impact of candidate genes on synaptic transmission, brain development and behavior.

The Kaplan laboratory has shown that worm muscles, when activated, produce a signal that inhibits the nerve cells impinging upon them. This ‘reverse’ synaptic signal is mediated by neurexin and neuroligin. Kaplan and colleagues plan to use this simple system to assess the importance of other candidate genes for neurexin- and neuroligin-mediated inhibition of brain signaling in autism.

The ultimate goal of these experiments is to determine the precise mechanism by which neurexin and neuroligin modify the function of the synapse, and to determine whether (and how) other candidate genes contribute to this process.