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DEVELOPMENT OF PHYSIOLOGICAL FUNCTION OF VISUAL CORTEX

视觉皮层生理功能的发育

基本信息

批准号：
12210014
负责人：
TSUMOTO Tadaharu
金额：
$ 69.7万
依托单位：
OSAKA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2004
项目状态：
已结题

项目摘要

In this research project we attempted to elucidate a role of brain-derived neurotrophic factor (BDNF) in development of neuronal circuits of the cerebral cortex. In 2000 and 2001, we investigated a possible contribution of BDNF in formation of ocular dominance (OD) columns in kitten visual cortex, and found that BDNF expands the size of OD columns. Also, we found that BDNF is released from presynaptic neurons and transferred to postsynaptic neurons in an activity-dependent manner. In 2002 we studied a possible involvement of BDNF in long-term depression (LTD) of synaptic transmission in visual cortex. We found that BDNF, which was exogenously applied to visual cortical slices prevented prolonged, low-frequency stimulation (LFS) of afferents from inducing LTD at synapses of cortical layer II/III neurons. Also we found that in the more physiological in vivo condition, LFS did not induce LTD because of the presence of endogenous BDNF in visual cortex. In 2003 and 2004 we tested whether BDNF has any action on development of GABAergic, inhibitory neurons using neuron culture preparations or visual cortical slices of GAD67-GFP knock-in mice. We found that BDNF promotes morphological and functional development of postsynaptic, GABAergic neurons. Because GABAergic neurons cannot produce BDNF by themselves and thus depends on BDNF which is transferred from other excitatory neurons in an activity dependent manner, the dependency of development of immature neuronal circuits on neuronal activity is ascribable mostly if not all to the dependency of development of GABAergic neurons on BDNF.

在这项研究中，我们试图阐明脑源性神经营养因子(BDNF)在大脑皮层神经元回路发育中的作用。2000年和2001年，我们研究了脑源性神经营养因子在猫视皮层优势眼柱形成中的可能作用，发现脑源性神经营养因子扩大了眼优势柱的大小。我们还发现，BDNF是从突触前神经元释放出来的，并以一种活动依赖的方式转移到突触后神经元。2002年，我们研究了脑源性神经营养因子在视皮层突触传递的长期抑制(LTD)中的可能作用。我们发现，外源性应用于视皮层脑片的BDNF可阻止对传入神经元的长时间低频刺激(LFS)在皮层II/III层神经元的突触诱导LTD。我们还发现，在更生理的活体条件下，LFS不会诱发LTD，因为在视觉皮质中存在内源性BDNF。2003年和2004年，我们使用神经元培养制剂或GAD67-GFP敲入小鼠的视皮层切片，测试了BDNF是否对GABA能抑制神经元的发育有任何作用。我们发现BDNF促进突触后GABA能神经元的形态和功能发育。由于GABA能神经元本身不能产生BDNF，因此依赖于从其他兴奋性神经元传入的BDNF，因此，未成熟神经元回路的发育对神经元活动的依赖可以归因于GABA能神经元的发育对BDNF的依赖。