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

在发育中的视皮层，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性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质中一种形式的突触可塑性，即长期抑制(LTD)。在这个项目中，我们试图利用全细胞膜片钳记录技术在幼年大鼠的视皮层脑片上阐明BDNF的这种阻断作用的机制。我们发现：1)如果在静息水平对突触后神经元进行电压钳制，在1赫兹长时间重复刺激10-15分钟并不能可靠地诱导LTD；2)对于LTD，突触后神经元应该与低频输入一起去极化；3)外源性BDNF在20 ng/ml时阻断LTD，这是由这种低频联合刺激所诱导的；4)内源性BDNF起作用以防止没有突触后去极化的低频输入引起LTD；以及5)BDNF的这种作用是通过激活突触前部位TrkB受体的酪氨酸激酶来介导的。

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.