Koyanagi Yuko, Yamamoto Kiyofumi, Kitano Kouhei, Kajiwara Mie, Kobayashi Masayuki
Department of Anesthesiology, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-Ku, Tokyo, 101-8310, Japan.
Division of Immunology and Pathobiology, Dental Research Center, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-Ku, Tokyo, 101-8310, Japan.
Pflugers Arch. 2025 May;477(5):707-717. doi: 10.1007/s00424-025-03074-8. Epub 2025 Mar 14.
Cerebrocortical neurons receive glutamatergic inputs via thalamocortical projections, and their activities are simultaneously controlled by GABAergic interneurons. Few studies have demonstrated the difference in the amplitude of evoked excitatory postsynaptic currents (EPSCs) via thalamocortical projections onto glutamatergic excitatory (ENs) and GABAergic inhibitory neurons (INs); the strength of excitation among neural subtypes varies among sensory cortices. The present study aimed to reveal the profile of thalamocortical inputs to ENs and inhibitory neurons in the insular cortex (IC) by evaluating the amplitude and latency of EPSCs evoked in the connection from the ventroposteromedial (VPM) thalamic nucleus to the IC. Whole-cell patch-clamp recordings were prepared from ENs, fast-spiking neurons (FSNs), and non-fast-spiking neurons (NFSNs) in the middle layers (layer 4 and adjacent layers) of the IC. Photostimulation-induced EPSCs (pEPSCs) were evoked via the selective activation of thalamocortical axons via optogenetics. All the neuronal subtypes received direct excitatory inputs from the VPM, and pEPSCs recorded from FSNs had the greatest amplitude and shortest latency compared with those recorded from ENs and NFSNs. Under current-clamp conditions, FSNs almost invariably exhibited action potentials responding to photostimulation, whereas ENs and NFSNs often showed the failure of action potential induction. In addition to excitatory inputs, some neurons exhibited pEPSCs followed by outward GABA receptor-mediated currents, which curtailed the pEPSC peak and aligned the timing of the action potential to photostimulation. These results suggested that FSNs play a role in the feedforward inhibition of EN activity in the upper layer of the IC. (244 words).
大脑皮质神经元通过丘脑皮质投射接收谷氨酸能输入,其活动同时受GABA能中间神经元的控制。很少有研究证明通过丘脑皮质投射到谷氨酸能兴奋性(ENs)和GABA能抑制性神经元(INs)上诱发的兴奋性突触后电流(EPSCs)幅度的差异;神经亚型之间的兴奋强度在不同感觉皮层中有所不同。本研究旨在通过评估从腹后内侧(VPM)丘脑核到岛叶皮质(IC)的连接中诱发的EPSCs的幅度和潜伏期,揭示丘脑皮质向IC中的ENs和抑制性神经元输入的情况。从IC中层(第4层和相邻层)的ENs、快发放神经元(FSNs)和非快发放神经元(NFSNs)制备全细胞膜片钳记录。通过光遗传学选择性激活丘脑皮质轴突诱发光刺激诱导的EPSCs(pEPSCs)。所有神经元亚型都接受来自VPM的直接兴奋性输入,与从ENs和NFSNs记录的pEPSCs相比,从FSNs记录的pEPSCs幅度最大、潜伏期最短。在电流钳条件下,FSNs几乎总是表现出对光刺激有反应的动作电位,而ENs和NFSNs经常显示动作电位诱导失败。除了兴奋性输入外,一些神经元表现出pEPSCs,随后是外向GABA受体介导的电流,这缩短了pEPSC峰值,并使动作电位的时间与光刺激对齐。这些结果表明,FSNs在IC上层对EN活动的前馈抑制中起作用。