Pan Wenlu, Pan Jing, Zhao Yan, Zhang Hongzheng, Tang Jie
Department of Physiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
Functional Nucleic Acid Basic and Clinical Research Center, Department of Physiology, School of Basic Medical Sciences, Changsha Medical College, Changsha, China.
Front Neurosci. 2021 Oct 6;15:749923. doi: 10.3389/fnins.2021.749923. eCollection 2021.
Serotonin transporter (SERT) modulates the level of 5-HT and significantly affects the activity of serotonergic neurons in the central nervous system. The manipulation of SERT has lasting neurobiological and behavioral consequences, including developmental dysfunction, depression, and anxiety. Auditory disorders have been widely reported as the adverse events of these mental diseases. It is unclear how SERT impacts neuronal connections/interactions and what mechanism(s) may elicit the disruption of normal neural network functions in auditory cortex. In the present study, we report on the neuronal morphology and function of auditory cortex in SERT knockout (KO) mice. We show that the dendritic length of the fourth layer (L-IV) pyramidal neurons and the second-to-third layer (L-II/III) interneurons were reduced in the auditory cortex of the SERT KO mice. The number and density of dendritic spines of these neurons were significantly less than those of wild-type neurons. Also, the frequency-tonotopic organization of primary auditory cortex was disrupted in SERT KO mice. The auditory neurons of SERT KO mice exhibited border frequency tuning with high-intensity thresholds. These findings indicate that SERT plays a key role in development and functional maintenance of auditory cortical neurons. Auditory function should be examined when SERT is selected as a target in the treatment for psychiatric disorders.
血清素转运体（SERT）调节5-羟色胺（5-HT）水平，并显著影响中枢神经系统中血清素能神经元的活性。对SERT的操控会产生持久的神经生物学和行为后果，包括发育功能障碍、抑郁和焦虑。听觉障碍作为这些精神疾病的不良事件已被广泛报道。目前尚不清楚SERT如何影响神经元连接/相互作用，以及何种机制可能引发听觉皮层正常神经网络功能的破坏。在本研究中，我们报告了SERT基因敲除（KO）小鼠听觉皮层的神经元形态和功能。我们发现，SERT KO小鼠听觉皮层中第四层（L-IV）锥体神经元和第二层至第三层（L-II/III）中间神经元的树突长度缩短。这些神经元的树突棘数量和密度显著低于野生型神经元。此外，SERT KO小鼠初级听觉皮层的频率-音频定位组织受到破坏。SERT KO小鼠的听觉神经元表现出具有高强度阈值的边界频率调谐。这些发现表明，SERT在听觉皮层神经元的发育和功能维持中起关键作用。在将SERT选作精神疾病治疗靶点时，应检查听觉功能。
