Sugimura Taketoshi, Yoshimura Yumiko, Komatsu Yukio
Department of Neuroscience, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan.
Division of Visual Information Processing, National Institute for Physiological Sciences, National Institutes for Natural Sciences, Okazaki 444-8585, Japan; Department of Physiological Sciences, The Graduate University for Advanced Studies, Okazaki 444-8585, Japan.
Neurosci Res. 2015 Jul;96:37-44. doi: 10.1016/j.neures.2015.02.005. Epub 2015 Feb 17.
Monocular deprivation produces depression and potentiation of visual responses evoked in visual cortical neurons by stimulation of deprived and nondeprived eyes, respectively, during the critical period of ocular dominance plasticity. Our previous studies suggested that T-type Ca(2+) channel-dependent long-term potentiation (LTP), induced by 2 Hz stimulation, mediates the potentiation of visual responses. However, it was proposed that the experience-dependent response potentiation is mediated by tumor necrosis factor-α (TNFα)-dependent homeostatic synaptic scaling but not by Hebbian synaptic plasticity, because the potentiation was absent in TNFα knockout (TNFα-KO) mice. In this study, we investigated whether TNFα is required for LTP induced by 2 Hz stimulation using visual cortical slices prepared from critical period mice and rats. The production of LTP was prevented by pharmacological blockade of TNFα in rats and mice. LTP production was also prevented by an inhibitor of TNFα-converting enzyme that converts membrane-bound TNFα to soluble TNFα. In TNFα-KO mice, LTP did not occur and was rescued by exogenous soluble TNFα. Soluble TNFα was required for LTP production only during a restricted time window soon after 2 Hz stimulation. These results strengthen the view that T-type Ca(2+) channel-dependent LTP contributes to the potentiation of nondeprived eye responses following monocular deprivation.
在眼优势可塑性的关键期，单眼剥夺分别导致视觉皮层神经元对剥夺眼和未剥夺眼刺激所诱发的视觉反应出现抑制和增强。我们之前的研究表明，由2赫兹刺激诱导的T型Ca(2+)通道依赖性长时程增强（LTP）介导了视觉反应的增强。然而，有人提出，依赖经验的反应增强是由肿瘤坏死因子-α（TNFα）依赖性的稳态突触缩放介导的，而非由赫布式突触可塑性介导，因为在TNFα基因敲除（TNFα-KO）小鼠中不存在这种增强。在本研究中，我们使用从关键期小鼠和大鼠制备的视觉皮层切片，研究了2赫兹刺激诱导的LTP是否需要TNFα。在大鼠和小鼠中，TNFα的药理学阻断可阻止LTP的产生。将膜结合型TNFα转化为可溶性TNFα的TNFα转换酶抑制剂也可阻止LTP的产生。在TNFα-KO小鼠中，LTP未出现，而外源性可溶性TNFα可挽救这种情况。可溶性TNFα仅在2赫兹刺激后不久的一个有限时间窗口内是LTP产生所必需的。这些结果强化了这样一种观点，即T型Ca(2+)通道依赖性LTP有助于单眼剥夺后未剥夺眼反应的增强。
