July 10, 2024
Keio University School of Medicine
A research group led by Professor Michisuke Yuzaki and Associate Professor Wataru Kakegawa of the Department of Physiology, Keio University School of Medicine, has discovered through experiments in mice that at synapses connecting nerve cells in the brain, "glutamate receptors"—responsible for information transmission—also function as synapse-forming molecules that induce the formation and maintenance of the synapses themselves, thereby regulating memory and learning.
In our brains, neural circuits that support various higher brain functions are constructed by nerve cells connecting with each other via synapses. Clarifying the function of molecules responsible for synapse formation is a crucial fundamental issue for elucidating higher brain functions and the pathophysiology of neuropsychiatric disorders.
This research group had previously discovered synapse-forming molecules such as C1ql1 and Bai3, using the cerebellum, which supports "motor memory," as a model. The current discovery revealed that kainate-type glutamate receptors (KARs), previously thought to be responsible for synaptic information transmission by functioning as ion channels, also form a complex with C1ql1 and Bai3 to act as synapse-forming molecules. In genetically modified mice lacking KARs, synapse formation was impaired, and motor learning ability was significantly reduced. Furthermore, it was confirmed that when KARs lacking the ion channel domain were introduced into these mutant mice, new synapses were formed even in the mature brain, and memory ability dramatically improved.
Mutations in KAR genes have been reported in many neuropsychiatric disorders, such as epilepsy and schizophrenia. Therefore, the findings from this study regarding the synapse-forming ability of KARs are expected to potentially lead to an understanding of the pathophysiology of these disorders and the development of new treatments.
The results of this research were obtained through a joint study with Professor Juan Lerma and his colleagues at the Spanish National Research Council-Miguel Hernández University, and were published in the online early edition of the American scientific journal Cell Reports (online early edition) on July 9, 2024, at 11:00 a.m. (US Eastern Time).
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