Blocking action of neurotrophin on long-term depression in developing visual cortex

神经营养素对视觉皮层发育中长期抑郁的阻断作用

• 批准号: 09480241
• 负责人: TSUMOTO Tadaharu
• 金额: $ 8.32万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09480241/
• 关键词: Brain; Neural circuits; Neurotrophin; Neuron; Synapse; Development; Long-term depression; Long-term potentiation

In the developing visual cortex, neurotrophins such as brain-derived neurotrophic factor (BDNF) are suggested to play a role in activity-dependent plasticity of synaptic function. In particular, BDNF has been suggested to block a form of synaptic plasticity, long-term depression (LTD), in visual cortex. In this project we attempted to elucidate mechanisms underlying such a blocking action of BDNF using the whole-cell patch-clamp recording technique in visual cortical slices prepared from young rats. We found that 1) long-lasting, repetitive stimulation at 1 Hz for 10-15 min that was previously reported to induce LTD did not reliably induce LTD if postsynaptic neurons were voltage-clamped at the resting level, 2) to induced LTD, postsynaptic neurons should be depolarized in conjunction with low-frequency inputs, 3) exogenous BDNF at 20 ng/ml blocked LTD which is to be induced by such low-frequency, conjunctive stimulation, 4) endogenous BDNF served so as to prevent low-frequency inputs without postsynaptic depolarization from inducing LTD, and 5) such an action of BDNF was mediated by an activation of tyrosine kinases of TrkB receptors in presynaptic sites.

在发育中的视觉皮层中，神经营养因子如脑源性神经营养因子（BDNF）被认为在突触功能的活动依赖性可塑性中发挥作用。特别是，BDNF 被认为可以阻断视觉皮层中的一种突触可塑性，即长期抑制 (LTD)。在这个项目中，我们尝试使用全细胞膜片钳记录技术在幼鼠制备的视觉皮层切片中阐明 BDNF 阻断作用的机制。我们发现，1）如果突触后神经元在静息水平被电压钳位，则先前报告的 1 Hz 持续 10-15 分钟的持久、重复刺激 10-15 分钟并不能可靠地诱导 LTD，2）为了诱导 LTD，突触后神经元应与低频输入结合去极化，3）20 时的外源 BDNF ng/ml 阻断了由这种低频、结性刺激诱导的 LTD，4) 内源性 BDNF 的作用是防止没有突触后去极化的低频输入诱导 LTD，5) BDNF 的这种作用是由突触前位点 TrkB 受体的酪氨酸激酶激活介导的。

项目成果

Kimura,F.,Otsu,Y.and Tsumoto,T.: "Presynaptically silent synapses:Spontaneously active terminals without stimulus-evoked release demonstrated in cortical autapses." J.Neurophysiol.77. 2805-2815 (1997)

Kimura, F., Otsu, Y. 和 Tsumoto, T.：“突触前沉默突触：皮层自动突触中表现出的自发活动末梢，没有刺激诱发的释放。”

Taniguchi, N., Takada, N., Kumura, E., Kimura, F.and Tsumoto, T.: "Actions of BDNF on evoked and spontaneous EPSCs dissociate with maturation of neurones cultured from rat visual cortex."Journal of Physiology (London). 527. 579-592 (2000)

Taniguchi, N.、Takada, N.、Kumura, E.、Kimura, F. 和 Tsumoto, T.：“BDNF 对诱发和自发 EPSC 的作用与大鼠视觉皮层培养的神经元的成熟分离。”生理学杂志（

Hata,Y., Tsumoto,T. and Stryker,M.P.: "Selective pruning of more active afferents when cat visual cortex is pharmacologically inhibited."Neuron. 22. 375-381 (1999)

Hata，Y.，津本，T.

Kumura, E., Kimura, F., Taniguchi, N.and Tsumoto, T.: "Brain-derived neurotrophic factor blocks long-term depression in solitary neurones cultured from rat visual cortex."Journal of Physiology (London). 524. 195-204 (2000)

Kumura, E.、Kimura, F.、Taniguchi, N. 和 Tsumoto, T.：“脑源性神经营养因子可阻断从大鼠视觉皮层培养的孤立神经元的长期抑制。”生理学杂志（伦敦）。

Kinoshita, S., Yasuda, H., Taniguchi, N.et al.: "Brain-derived neurotrophic factor prevents low-frequency inputs from inducing long-term depression in the developing visual cortex."Journal of Neuroscience. 19. 2122-2130 (1999)

Kinoshita, S.、Yasuda, H.、Taniguchi, N.等人：“脑源性神经营养因子可防止低频输入在发育中的视觉皮层中诱发长期抑郁。”《神经科学杂志》。