The connections between neurons—called synapses—are quite literally the stuff of learning. The dynamics of how two neurons connect at the synapse determines the quantity and quality of information flow between those two cells. Genes that encode certain synaptic proteins, such as neurexin and neuroligin, are sometimes atypical in individuals with ASD. These proteins act like a sort of glue to keep two neurons in close contact and their shared synapse functioning smoothly.
We can reason from the studies of genetics and animal models developed to examine autism-associated genes that disturbances in proteins like neuroligin and neurexin disrupt individual neuron-to-neuron communication and eventually the dynamics of larger functional circuits in the brain. What we don’t understand is how, exactly, a mutation in a neuroligin protein leads to a disruption in communication. This level of detail is exactly what we must understand to develop targeted therapeutics. However, until recently we lacked the ability to visualize, in living tissue, neuroligin and neurexin proteins interacting as the synapse matures.
In a new report in the prestigious journal, Cell, Autism Speaks’ funded postdoctoral fellow Amar Thyagarajan, Ph.D., at the Picower Institute of MIT, demonstrates a new technique for following the dynamic development and function of synapses. Dr. Thyagarajan, along with his mentor Alice Ting, Ph.D, labeled neuroligin and neurexin with a special tag that glows when the two interact. The researchers observed how the activity of the neurons affects the neuroligin-neurexin connection as a new synapse matures. As the synapse connecting the two neurons strengthens, the researchers were able to see the recruitment of new neuroligin-neurexin pairs into the synapse as well as other proteins that are needed to reinforce the synapse.
With each piece of the autism biology puzzle uncovered, new directions for developing targeted therapeutics are revealed. The complete network of interacting proteins that contribute to a functional synapse is dizzying in its complexity. However, each time scientists identify a new string on which to tug, we learn more about how this complex network is connected. The ability to observe the active development of synapses will undoubtedly factor into future discoveries, paying dividends for some time to come.
Reference: “Imaging Activity-Dependent Regulation of Neurexin-Neuroligin Interactions Using trans-Synaptic Enzymatic Biotinylation,” by Amar Thyagarajan and Alice Y. Ting. Cell, 7 October, 2010.
For more information about the science of the synapse and targeted therapeutics that have emerged from synaptic physiology, check out Seaside Therapeutics.