Huang Ying, Yoon Kristopher, Ko Ho, Jiao Song, Ito Wataru, Wu Jian-Young, Yung Wing-Ho, Lu Bai, Morozov Alexei
Unit on Behavioral Genetics, Laboratory of Molecular Pathophysiology, National Institute of Mental Health, National Institutes of Health, Maryland 20892, USA Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.
Unit on Behavioral Genetics, Laboratory of Molecular Pathophysiology, National Institute of Mental Health, National Institutes of Health, Maryland 20892, USA.
Cereb Cortex. 2016 Feb;26(2):576-85. doi: 10.1093/cercor/bhu209. Epub 2014 Sep 21.
Gamma-frequency oscillatory activity plays an important role in information integration across brain areas. Disruption in gamma oscillations is implicated in cognitive impairments in psychiatric disorders, and 5-HT3 receptors (5-HT3Rs) are suggested as therapeutic targets for cognitive dysfunction in psychiatric disorders. Using a 5-HT3aR-EGFP transgenic mouse line and inducing gamma oscillations by carbachol in hippocampal slices, we show that activation of 5-HT3aRs, which are exclusively expressed in cholecystokinin (CCK)-containing interneurons, selectively suppressed and desynchronized firings in these interneurons by enhancing spike-frequency accommodation in a small conductance potassium (SK)-channel-dependent manner. Parvalbumin-positive interneurons therefore received diminished inhibitory input leading to increased but desynchronized firings of PV cells. As a consequence, the firing of pyramidal neurons was desynchronized and gamma oscillations were impaired. These effects were independent of 5-HT3aR-mediated CCK release. Our results therefore revealed an important role of 5-HT3aRs in gamma oscillations and identified a novel crosstalk among different types of interneurons for regulation of network oscillations. The functional link between 5-HT3aR and gamma oscillations may have implications for understanding the cognitive impairments in psychiatric disorders.
γ 频段振荡活动在跨脑区信息整合中发挥着重要作用。γ 振荡的破坏与精神疾病的认知障碍有关，5-羟色胺 3 型受体（5-HT3Rs）被认为是精神疾病认知功能障碍的治疗靶点。利用 5-HT3aR-EGFP 转基因小鼠品系，并在海马切片中通过卡巴胆碱诱导 γ 振荡，我们发现 5-HT3aRs 的激活，其仅在含胆囊收缩素（CCK）的中间神经元中表达，通过以小电导钾（SK）通道依赖的方式增强动作电位频率适应性，选择性地抑制并使这些中间神经元的放电去同步化。因此，小白蛋白阳性中间神经元受到的抑制性输入减少，导致 PV 细胞的放电增加但去同步化。结果，锥体神经元的放电去同步化，γ 振荡受损。这些效应独立于 5-HT3aR 介导的 CCK 释放。因此，我们的结果揭示了 5-HT3aRs 在 γ 振荡中的重要作用，并确定了不同类型中间神经元之间一种新的相互作用，用于调节网络振荡。5-HT3aR 与 γ 振荡之间的功能联系可能对理解精神疾病中的认知障碍具有重要意义。
