Highlights from IMFAR 2008:
Friday, May 16
Thomas Bourgeron
Human Genetics and Cognitive Functions, Institut Pasteur
Title: Synaptic and clock genes in autism spectrum disorders
Overview: Autism spectrum disorders (ASD) are characterized by impairments in communication skills and social interaction, as well as restricted, repetitive and stereotyped patterns of behavior. Our genetic studies point to one synaptic pathway, including cell adhesion molecules (neuroligins NLGN3, NLGN4 and neurexins NRXN1) and scaffolding proteins (SHANK3) associated with the disorder. This pathway is crucial for synapse formation/maintenance as well as correct balance between GABAergic and glutamatergic synaptic currents. Interestingly, mice with neuroligin mutations show reduced social interactions and ultrasonic vocalizations. Beside this synaptic pathway, we recently reported genetic mutations altering melatonin synthesis in ASD. Melatonin plays a key role in the regulation of circadian rhythms such as sleep-wake cycles and was shown to modulate GABAergic currents, as well as neurite and memory formation in different animals such as fish, birds, and mammals. Based on these results, we propose that, in some cases, ASD could be the consequence of an excess of GABAergic currents in specific regions of the brain. This excess of inhibitory current could be the consequence of an alteration of synaptic genes revealed or amplified by an alteration of the circadian rhythms. Hence, a better characterization of the interplay between synaptic and clock genes may shed light on several atypical features that are frequently observed in individuals with ASD such as sleep alterations and memory storage/formation.
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