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

在发育中的视觉皮层中，脑源性神经营养因子（BDNF）等神经营养因子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突触可塑性的一种形式——长期抑制（LTD）。在这个项目中，我们试图阐明BDNF阻断作用的机制，使用全细胞膜片钳记录技术在幼鼠的视觉皮层切片中进行记录。我们发现，1)先前报道的长时间、1 Hz、持续10-15分钟的重复刺激，如果在静息水平上对突触后神经元施加电压，则不能可靠地诱导LTD； 2)为了诱导LTD，突触后神经元应与低频输入一起去极化；3)20 ng/ml的外源性BDNF阻断了这种低频联合刺激诱导的LTD。4)内源性BDNF的作用是防止无突触后去极化的低频输入诱导LTD， 5) BDNF的这种作用是通过激活突触前位点TrkB受体的酪氨酸激酶介导的。

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.