14 DAY TRIAL // Researchers at MIT found a way of observing molecules at work inside living brain cells, which also explains the molecular mechanisms of synapse formation.
The studies carried out by researchers Amar Thyagarajan and Alice Y. Ting, affiliated with MIT's Picower Institute for Learning and Memory and the MIT Department of Chemistry, could also help clear the mystery of synapses malfunction in diseases like autism or Fragile X syndrome.
In order to observe molecules inside the brain cells, the researchers studied the interaction between neurexin and neuroligin proteins from the neuron's surface, which are two of the many adhesion molecules in the brain that control synapse formation, growth, function and plasticity.
Not only do they work as some kind of glue holding neurons together, but they also mediate signaling for recruiting the appropriate molecular components for the pre- and postsynaptic cells.
The new technique is called BLINC, or Biotin Labeling of Intercellular Contacts, and it creates a fluorescent signal every time neurexin and neuroligin interact.
Amar Thyagarajan, Autism Speaks Postdoctoral Fellow in the laboratory of Alice Y. Ting, an associate professor of chemistry explained that “the only way for a BLINC signal to occur is when two neurons contact each other.”
As this new method is more accurate and sensitive than the other existing ones, the scientists discovered that some protein-protein interactions can affect early phases of synapse maturation.
This finding will contribute to better understanding the way that two neighboring neurons form a synapse, and give more information about the dynamics of proteins in synapses, one minute at a time.
Amar Thyagarajan said that “how nascent contacts mature into excitatory or inhibitory synapses is an area of intense interest.
“Trans-synaptic signaling complexes seem like a good place to start looking for clues to this process since they mediate signaling into the pre- and post-synaptic cells during this process.”
Scientists knew that neurexins and neuroligins are important for synapse maturation, but they never understood their exact function.
“Our motivation was that if we could come up with a way to directly observe this complex, then maybe we could better understand its function in synapse maturation,” said Thyagarajan.
“We developed BLINC to visualize this complex in live synapses in culture.
“We then used BLINC in different modalities to discover that synaptic activity causes the neurexin-neuroligin complex to grow in size,” he explined.
“This growth is necessary for the recruitment of AMPA receptors to young synapses, [and as the] AMPA receptor recruitment is a hallmark of excitatory synapse maturation, our study demonstrated how a trans-synaptic complex can affect early phases of synapse maturation.”
The study was published in the October 7 issue of Cell.