There are many different types of synapses that form between neurons, including ‘excitatory’ and ‘inhibitory,’ and scientists are still unsure of the exact mechanisms by which these structures are formed.
The Biochemistry Laboratory at Colorado State University has revealed insights into this question by showing that the types of chemicals released from synapses ultimately direct the types of synapses that form between neurons.
Soham Chanda, an assistant professor in the Department of Biochemistry and Molecular Biology, led the study published in Nature Communications that demonstrates the ability of enzymatic means to change the identity of synapses between neurons in vitro and in vivo.
Other senior scientists who have contributed to the project include Thomas Sudhoff of Stanford University and Matthew Zoe Friedman of the University at Buffalo.
In the lab, Chanda and colleagues were able to switch synapses between excitatory and inhibitory types by causing neurons to express only a few genes that caused a series of changes in the synapse machinery. Such a breakthrough could have major implications for treating brain diseases caused by malfunctions in the processing and exchange of synaptic information.
“We know very little about how the human brain works, and we need to understand how neurons communicate with one another,” Chanda explained.”Understanding brain disorders requires understanding the fundamental mechanisms of synapse formation and maintenance.”
Their results show that cell adhesion proteins expressed in the synaptic junction region are not the only providers of synaptic function, as some belief; Instead, chemicals called neurotransmitters that are released from the presynaptic site (where information comes from) appear to play a major role in controlling what types of synapses form and where.
The UCSD team demonstrated the ability of human stem cell-derived neurons to produce specific types of synaptic connections through the controlled release of specific neurotransmitters. Collaborators at the University at Buffalo demonstrated the same phenomenon in the brains of live mice.
“Synapses need a lot of other machinery; neurons take care of all of that and turn excitatory synapses into inhibitory synapses—a fundamental change in their identity,” said Zhou Friedman.
“No other cell type in the human body has the same level of functional complexity closely related to their shape and structure,” says Chanda.
The students who performed the majority of the experiments were co-authors Scott Burlingham and Lindsey Peterkin of California State University, and Nicole Wong of the University at Buffalo.
Scott R. Burlingham, Nicole F. Wong, Lindsay Peterkin, Lily Lubow, Carolina Dos Santos Passos, Orion Benner, Michael Ghebrial, Thomas P. Cast, Matthew A. Xu-Friedman, Thomas C. Südhof, Soham Chanda. Induction of synapse formation by de novo neurotransmitter synthesis. Nature Communications, 2022; 13 (1) DOI: 10.1038/s41467-022-30756-z