Revealing How Neural Circuits Cause Anxiety: A Cover Story on Cell Reports Following Taiwan–Europe–U.S.A. Cooperation

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Lien Cheng-chang, a distinguished professor at the Institute of Neuroscience, NYCU, and his research team had devoted themselves to studying the neural circuits in the hippocampus that regulates and control anxious behavior. They subsequently identified the neural mechanisms through which the hippocampus mossy cells resist anxiety. The remarkable research results were published as the cover article in Cell Reports (a prestigious international journal) on September 14, 2021.

In recent years, the busy and fast-paced lifestyle has resulted in increased incidence of emotional disorders caused by various reasons, among which the percentage of anxiety disorder cases has been rising annually. Professor Lien indicated that recent studies have revealed the crucial roles played by the hippocampus on regulating emotions. The hippocampus transmits signals from the dentate gyrus (its first stop) through neural nerves to its final stop, where scientists have found cells related to anxiety control. Nevertheless, the mechanisms through which hippocampal neural circuits transmit signals from the dentate gyrus to the final stop and thereby regulate and control anxiety behavior remain a fascinating topic to be explored.

In animal experiments, Professor Lien’s research team discovered that mossy cells, a type of neural cells in the dentate gyrus, can be used as indicators of anxiety level. Because mossy cell activity changes under varying environmental stress, Professor Lien’s research team employed optogenetics and chemical genetics to control mossy cell activity in the dentate gyrus, and used juxtacellular recordings to gain insight into the mechanisms through which mossy cells regulate and control hippocampal neural circuits. The results showed that activated mossy cells increased inhibitory signals in the dentate gyrus to decrease the output and transmission of anxiety-related neural signals in the hippocampus. Thus, activating mossy cells can effectively alleviate anxiety behavior in animals.

Professor Lien remarked that this study unveiled the roles played by the hippocampus on anxiety behavior, and hoped that by regulating and controlling mossy cell activity, the research results can be translated and applied in clinical practice in the future, benefiting the control on anxiety disorders clinically.

This study was primarily conducted by Wang Kai-yi, a Ph.D. student in Professor Lien’s lab and the first author of this study. Data analyses were performed by Chen Chun-chung (adjunct assistant professor at the Institute of Neuroscience) and Wu Che-wei (a Ph.D. student). Transgenic mice were provided by Professor Kazu Nakazawa from the University of Alabama at Birmingham. Wang studied  living nerve cell recording and staining techniques at Professor Gábor Tamás’ lab at the University of Szeged, Hungary during a Taiwan–Hungary Bilateral Personnel Exchanges Project hosted by the MOST-HAS.

Professor Lien used his high-quality neuroscience R&D capacity, integrated optoelectronic technology, and engaged in transnational cooperation to allow Taiwan’s brain technology R&D results to shine on the international stage. Over the past few years, he has utilized his exceptional coordination abilities to bring scholars from different domains together and host the Taiwan Brain Technology Research Project, producing outstanding results. In the future, Professor Lien will continue to lead Taiwan’s brain science research in its strive toward the academic “peak” worldwide.

Cover story: The cover of this journal was designed by artist Tsai Yu-lin and Professor Tsai Yu-huan of the Institute of Microbiology & Immunology, NYCU. The Nerve cell “mossy cell” earned its name because the top of its dendrites is covered with moss-like dendritic spines. The cover describes how a mossy cell is similar to a lightning bolt at night, comparable to a researcher using optogenetic technology and a blue laser to activate a mossy cell, generating an electric current that enables the researcher to study how nerve signals are transmitted downstream.


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