DEVELOPMENT OF PHYSIOLOGICAL FUNCTION OF VISUAL CORTEX

在本研究中，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。在2000年和2001年，我们研究了BDNF在小猫视皮层眼优势（OD）柱形成中的可能作用，发现BDNF使OD柱扩大。此外，我们还发现BDNF从突触前神经元释放并以活动依赖的方式转移到突触后神经元。2002年我们研究了BDNF可能参与视皮层突触传递的长时程抑制（LTD）。我们发现，BDNF，这是外源性应用于视觉皮层切片防止长时间，低频刺激（LFS）的传入诱导LTD在皮层第II/III层神经元的突触。我们还发现，在更生理的体内条件下，LFS并没有诱导LTD，因为存在内源性BDNF在视觉皮层。在2003年和2004年，我们使用神经元培养物或GAD 67-GFP基因敲入小鼠的视皮层切片测试BDNF是否对GABA能抑制性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能神经元自身不能产生BDNF，因此依赖于以活动依赖性方式从其他兴奋性神经元转移的BDNF，未成熟神经元回路的发育对神经元活动的依赖性如果不是全部的话，也是大部分归因于GABA能神经元的发育对BDNF的依赖性。

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.