■ New small molecule visualization method driven by tissue fixation（Chem）2022.12.13

Nonaka H, Mino T, Sakamoto S, Oh JH, Watanabe Y, Ishikawa M, Tsushima A, Amaike K, Kiyonaka S, Tamura T, Aricescu AR, Kakegawa W, Miura E, Yuzaki M, Hamachi I. Revisiting PFA-mediated tissue fixation chemistry: FixEL enables trapping of small molecules in the brain to visualize their distribution changes. Chem 9:523-540, 2023. doi.org/10.1016/j.chempr.2022.11.005
Small molecules administered to adults、As a new technology that visualizes how and where in the brain it is distributed like a snapshot、We have developed a method for immobilizing small molecules using paraformaldehyde, which is often used in tissue fixation.。by this method、metabotropic glutamate receptor mGlu1、AMPA-type glutamate receptor、Succeeded in visualizing the localization pattern of dopamine receptors after ligand administration。This research was supported by ERATO/CREST.、It is a joint research with Nagoya University Seichu Lab.。

■Complement C3-complement factor D-C3a receptor signal、Controls cardiac remodeling in right heart failure（Nature commun）2022.9.15

This S, Hashimoto H, Yamakawa H, Kusumoto D, Akiba Y, Nakamura T, Momoi M, Komuro J, Katsuki T, Kimura M, Kishino Y, Kashimura S, Kunitomi A, Lachmann M, Shimojima M, Yozu G, Motoda C, Seki T, Yamamoto T, Shinya Y, Hiraide T, Kataoka M, Kawakami T, Suzuki K, Ito K, Yada H, Abe M, Osaka M, Tsuru H, Yoshida M., Sakimura K, Fukumoto Y, Yuzaki M, Fukuda K, Yuasa S. The complement C3-complement factor D-C3a receptor signalling axis regulates cardiac remodelling in right ventricular failure. Nat Commun. 13:5409, 2022.
right heart failure、play an important role in all types of heart failure、Its mechanism is still unknown and there is no specific treatment。In this paper、A group led by Dr. Yuasa of the Department of Cardiology revealed for the first time that Cfd and C3aR1 related to the alternative complement pathway control the onset of right heart failure.。Yuzuzaki Lab (Suzuki-kun)、Created conditional complement 3 (C3) knockout mice with Sakimura Laboratory, Niigata University、Contributed to testing this hypothesis。

■ Nano world in the brain seen by "inflating" the specimen（Neuron）2022.8.25

Nozawa K, Sogabe T, Hayashi A., Motohashi J, Miura E, Arai I, Them so M *. In vivo nanoscopic landscape of neurexin ligands underlying anterograde synapse specification. Neuron. 110:3168-3185, 2022.
by improving Expansion Microscopy (ExM), a high-resolution microscopy technique、Molecules that determine the individuality of synapses in the brain at the nano level (one millionth of a millimeter is one nanometer)：nm) revealed the structure of。
The neural network that underpins the functioning of the brain、Nerve cells are connected to each other by synapses。Various molecules that connect synapses are、Because it is concentrated in a narrow region of about 100 to 1000 nm in the synapse、Its detailed distribution cannot be observed with the resolution of conventional optical microscopes (approximately 200 nm).。there、Nozawa-kun, together with Hayashi-san、We further improved ExM, a technology that expands the specimen itself to about 1000 times its volume.、By optimizing for synaptic observation、For the first time, we succeeded in clarifying the structure and interrelationships of molecular groups that connect excitatory synapses in mouse neural networks at the nano-level.。According to the comment, 、A group of synaptic molecules that bind to neurexin (neurexin ligand)、It was discovered that they accumulate as units of ``nanodomains'' of several tens of nanometers each within synapses.。further、Depending on the type of neurexin present at the presynaptic site、It has been found that the arrangement of nanodomains of post-synaptic synaptic molecules and glutamate receptors is determined。
From the results of this research、The characteristics of synapses that support brain function、It turns out that each specialized synaptic molecule is created by interacting at the nano level.。These molecular groups have been reported to be associated with many psychiatric disorders and neurodevelopmental disorders.、It is expected that the results of this research will lead to an understanding of the pathogenesis of these diseases and the developmental mechanisms of normal neural circuits.。

■ Chemically activates G protein-coupled receptors（Common Nat）2022.6.16

Ojima K, Kakegawa W, Yamasaki T, Miura Y, Itoh M, Michibata Y, Kubota R, Doura T, Miura E, Nonaka H, Mizuno S, Takahashi S, Them so M *, Hamachi I *, Kiyonaka S* Coordination chemogenetics for activation of GPCR-type glutamate receptors in brain tissue. Nat Commun 13: 3167 (2022).
To understand how neural circuits in the brain work、There is a need for technology that selectively activates glutamate receptors, which are neurotransmitter receptors that control memory and learning.。In this research、While maintaining the original glutamate response ability、Developed a mutant glutamate receptor activated by an artificial compound。We created mice that actually expressed this mutant glutamate receptor in a specific cell type.、It was shown that administration of artificial compounds activates glutamate receptors in a cell-type-selective manner.。It is expected that the understanding of neural circuits will be accelerated by using this new technology "coordination chemogenetics method".。This research is conducted at Kiyonaka Lab., Nagoya University.、This is a joint research with Kyoto University Hamaji Lab.。