Hioki Hiroyuki, Sohn Jaerin, Nakamura Hisashi, Okamoto Shinichiro, Hwang Jungwon, Ishida Yoko, Takahashi Megumu, Kameda Hiroshi
Department of Cell Biology and Neuroscience, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan; Department of Morphological Brain Science, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Department of Morphological Brain Science, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan; Division of Cerebral Circuitry, National Institute for Physiological Sciences, 5-1 Higashiyama Myodaiji, Okazaki, Aichi 444-8787, Japan; Research Fellow of Japan Society for the Promotion of Science (JSPS), 5-3-1 Kojimachi, Chiyoda-ku, Tokyo 102-0083, Japan.
Brain Res. 2018 Sep 15;1695:18-30. doi: 10.1016/j.brainres.2018.05.029. Epub 2018 May 21.
Parvalbumin-positive (PV+) neurons in the cerebral cortex, mostly corresponding to fast-spiking basket cells, have been implicated in higher-order brain functions and psychiatric disorders. We previously demonstrated that the somatic compartment of PV+ neurons received inhibitory inputs mainly from vasoactive intestinal polypeptide (VIP)+ neurons, whereas inhibitory inputs to the dendritic compartment were derived mostly from PV+ and somatostatin (SOM)+ neurons. However, a substantial number of the axosomatic inputs have remained unidentified. Here we show preferential innervation of the somatic compartment of PV+ neurons by cholecystokinin (CCK)+ neurons in the mouse primary somatosensory cortex. CCK+ neurons, a minor population of GABAergic neurons (3.2%), displayed no colocalization with PV or SOM immunoreactivity but partial overlap with VIP immunoreactivity (27.7%). Confocal laser scanning microscopy observation of CCK+ synaptic inputs to PV+ neurons revealed that CCK+ neurons preferred the somatic compartment to the dendritic compartment of PV+ neurons and provided approximately 33% of the axosomatic inhibitory inputs to PV+ neurons. Additionally, 20.9% and 12.1% of the axosomatic inputs were derived from CCK+/VIP+ and CCK+/VIP-negative (-) neurons, presumably double bouquet and large basket cells, respectively. Furthermore, the densities of the axosomatic inputs from CCK+ and/or VIP+ neurons to PV+ neurons were not significantly different among the cortical layers. The present findings suggest that, by preferentially innervating the cell bodies of PV+ neurons, both CCK+/VIP- basket and CCK+/VIP+ double bouquet cells might efficiently interfere with action potential generation of PV+ neurons, and that the two types of CCK+ neurons might have a large impact on cortical activity through PV+ neuron inhibition.
大脑皮层中的小白蛋白阳性(PV+)神经元,大多对应快速放电篮状细胞,与高阶脑功能和精神疾病有关。我们之前证明,PV+神经元的胞体部分主要接收来自血管活性肠肽(VIP)+神经元的抑制性输入,而树突部分的抑制性输入大多来自PV+和生长抑素(SOM)+神经元。然而,大量的轴-体输入仍未明确。在这里,我们展示了胆囊收缩素(CCK)+神经元对小鼠初级体感皮层中PV+神经元胞体部分的优先支配。CCK+神经元是γ-氨基丁酸能神经元中的少数群体(3.2%),与PV或SOM免疫反应性无共定位,但与VIP免疫反应性有部分重叠(27.7%)。对PV+神经元的CCK+突触输入进行共聚焦激光扫描显微镜观察发现,CCK+神经元更倾向于PV+神经元的胞体部分而非树突部分,并为PV+神经元提供了约33%的轴-体抑制性输入。此外,轴-体输入的20.9%和12.1%分别来自CCK+/VIP+和CCK+/VIP阴性(-)神经元,推测分别为双花束细胞和大篮状细胞。此外,CCK+和/或VIP+神经元对PV+神经元的轴-体输入密度在各皮层层之间无显著差异。目前的研究结果表明,通过优先支配PV+神经元的细胞体,CCK+/VIP-篮状细胞和CCK+/VIP+双花束细胞可能有效地干扰PV+神经元的动作电位产生,并且这两种类型的CCK+神经元可能通过抑制PV+神经元对皮层活动产生重大影响。