Retrograde synaptic signaling by neurexin and neuroligin in C. elegans
Joshua Kaplan, Ph.D.
Massachusetts General Hospital
Functional brain imaging studies of individuals with autism suggest that brain activity in response to sensory stimuli is delayed, multisensory brain responses are integrated over a longer time frame, and activity across brain regions is less synchronous than in typically developing people.
Joshua Kaplan and his colleagues at Massachusetts General Hospital found that mutations in three genes linked to autism (NRXN, NLGN and MEF2) alter the kinetics of neurotransmitter release in the nematode C. elegans, prolonging the transmission of signals across synapses — the connections between cells in the brain1.
The researchers also showed that the duration of evoked responses is prolonged in ‘triple-knockout’ mice lacking neuroligins 1, 2 and 3. Thus, the effects of neuroligin and neurexin on synaptic response kinetics appear to be conserved across species. Kaplan’s work suggests that slower and more prolonged synaptic responses could contribute to the cognitive and developmental changes that occur in individuals with autism.
1: Hu Z. et al. Science 337, 980-984 (2012) PubMed
Award #: 177948