Study reveals possibility of changing the identity of synapses through enzymatic means

As you're reading this sentence, the cells in your brain, called neurons, are sending rapid-fire electrical signals between each other, transmitting information. They're doing so via tiny, specialized junctions between them called synapses.

There are many different types of synapses that form between neurons, including "excitatory" or "inhibitory," and the exact mechanisms by which these structures are generated remain unclear to scientists. A Colorado State University biochemistry lab has uncovered a major insight into this question by showing that the types of chemicals released from synapses ultimately guide which kinds of synapses form between neurons.

Soham Chanda, assistant professor in the Department of Biochemistry and Molecular Biology, led the study published in Nature Communications that demonstrates the possibility of changing the identity of synapses between neurons, both in vitro and in vivo, through enzymatic means. The other senior scientists who contributed to the project were Thomas Südhof of Stanford University and Matthew Xu-Friedman of the University at Buffalo.

In the lab, Chanda and colleagues were able to make synapses changes between excitatory and inhibitory types, using only enzymes, by making the neurons express just a few genes that induced a cascade of changes in the synapses' machinery. Such a breakthrough could have major implications for treating brain diseases that are caused by malfunctions in synaptic information processing and exchange.

We know very little about how the human brain functions, and at the center of it, we need to understand how neurons communicate with each other. Understanding the fundamental mechanisms of synapse formation and maintenance has tremendous implications in understanding brain disorders."

Soham Chanda, Assistant Professor, Department of Biochemistry and Molecular Biology

Their results show that the cell-adhesion proteins expressed in the synaptic junction area are not the only purveyors of the synapses' function, as some have thought; rather, chemicals called neurotransmitters that are released from the presynaptic site (where the information is coming from) also seem to play a major role in controlling which types of synapses form, and where.

The CSU team used stem cell-derived human neurons to demonstrate their ability to produce certain types of synaptic connections by controlled release of specific neurotransmitters. Collaborators at the University at Buffalo showed the same phenomenon in live mouse brains.

"Synapses need lots of other machinery; the neurons took care of all that and turned excitatory synapses into inhibitory ones – a fundamental change in their identity," Xu-Friedman said.

Chanda is fascinated by neurons, "because no other cell type in the human body has the same level of functional complexity that is tied so closely to their shape and structure."

The students who performed the majority of the experiments were co-authors Scott Burlingham and Lindsay Peterkin at CSU, and Nicole Wong at the University at Buffalo.

Source:
Journal reference:

Burlingham, S.R., et al. (2022) Induction of synapse formation by de novo neurotransmitter synthesis. Nature Communications. doi.org/10.1038/s41467-022-30756-z.

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