5‐HT6R null mutatrion induces synaptic and cognitive defects |
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Authors: | Zehui Sun Bingjie Wang Chen Chen Chenjian Li Yan Zhang |
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Affiliation: | 1. State Key Laboratory of Membrane Biology, College of Life Sciences, Peking University, Beijing China ; 2. PKU/IDG McGovern Institute for Brain Research, Beijing China ; 3. School of Life Sciences, Lanzhou University, Lanzhou China |
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Abstract: | Serotonin 6 receptor (5‐HT6R) is a promising target for a variety of human diseases, such as Alzheimer''s disease (AD) and schizophrenia. However, the detailed mechanism underlying 5‐HT6R activity in the central nervous system (CNS) is not fully understood. In the present study, 5‐HT6R null mutant (5‐HT6R−/−) mice were found to exhibit cognitive deficiencies and abnormal anxiety levels. 5‐HT6R is considered to be specifically localized on the primary cilia. We found that the loss of 5‐HT6R affected the Sonic Hedgehog signaling pathway in the primary cilia. 5‐HT6R−/− mice showed remarkable alterations in neuronal morphology, including dendrite complexity and axon initial segment morphology. Neurons lacking 5‐HT6R exhibited increased neuronal excitability. Our findings highlight the complexity of 5‐HT6R functions in the primary ciliary and neuronal physiology, supporting the theory that this receptor modulates neuronal morphology and transmission, and contributes to cognitive deficits in a variety of human diseases, such as AD, schizophrenia, and ciliopathies. |
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Keywords: | 5‐ HT6R, learning and memory, neuronal excitability, primary cilia |
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