August 25, 2022
Keio University School of Medicine
A group led by Professor Michisuke Yuzaki of the Department of Physiology, Keio University School of Medicine, and Kazuya Nozawa, a fourth-year student in the Doctoral Programs at the university's Graduate School of Medicine, has revealed the nanometer-scale (1 nanometer [nm] is one-millionth of a millimeter) structure of molecular groups that determine the identity of synapses in the brain by improving Expansion Microscopy (ExM), a high-resolution microscopy technique.
The neural networks underlying brain function are formed by nerve cells connecting with each other via synapses. The various molecules that connect synapses are densely packed within a narrow region of about 100–1000 nm, making it impossible to observe their detailed distribution with the resolution of conventional light microscopes (about 200 nm). Therefore, by further improving and optimizing the ExM technique—which expands the sample itself to about 1000 times its original volume—for synapse observation, the team has now succeeded for the first time in revealing the nanometer-scale structure and interrelationships of molecular groups that connect excitatory synapses in mouse neural networks. In particular, they discovered that synaptic molecular groups that bind to neurexin (neurexin ligands) assemble within the synapse in units of "nanodomains," each several tens of nanometers in size. Furthermore, they found that the type of neurexin present in the presynaptic terminal determines the arrangement of nanodomains of postsynaptic molecules and glutamate receptors.
The results of this study show that the identity of synapses supporting brain function is created by the nanometer-scale interaction of specialized synaptic molecules. As these molecular groups have been reported to be associated with many psychiatric and neurodevelopmental disorders, the findings of this research are expected to contribute to the understanding of the pathology of these diseases and the mechanisms of normal neural circuit development.
The results of this research were published in the online early edition of the American scientific journal Neuron on August 24, 2022, at 11:00 a.m. (US Eastern Time).
For the full press release, please see below.