Demonstration of long-range GABAergic connections distributed throughout the mouse neocortex
Demonstration of long-range GABAergic connections distributed throughout the mouse neocortex
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DOI：
10.1111/j.1460-9568.2005.03989.x
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发表时间：
2005-03-01
影响因子：
3.4
通讯作者：
Tamamaki, N
中科院分区：
文献类型：
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作者：
Tomioka, R;Okamoto, K;Tamamaki, N
新皮层中的γ -氨基丁酸（GABA）能神经元主要被认为是中间神经元，并被认为提供局部相互作用。然而，最近，谷氨酸脱羧酶（GAD）免疫细胞化学结合逆行标记实验揭示了gaba能投射神经元在新皮层的存在。我们采用gad67 -绿色荧光蛋白（GFP）敲入小鼠进行逆行标记和一种新的新皮层gaba能神经元标记方法进行轴突示踪，进一步研究gaba能投射神经元在新皮层的网络。快速蓝注射到初级体感觉、运动和视觉皮层后，许多gfp阳性神经元被逆行标记。这些神经元不仅在注射部位周围被标记，而且在距离注射部位很远的地方也被标记。在远离注射部位逆行标记的gaba能神经元中，绝大多数（91%）表现出生长抑素免疫反应性，且优先分布在第II层、第VI层和白质中。大多数gaba能投射神经元神经肽Y阳性（82%），神经元一氧化氮合酶阳性（71%）。我们通过追踪gfp标记的具有轴突分支的gaba能神经元，证实了远距离的预测。轴突分支可追溯至2mm。一些（n = 2 / 4）被证明跨越了区域边界。gaba能投射神经元优先接受新皮层输入。从这些结果，我们得出结论，gaba能投射神经元分布在整个新皮层，是皮质-皮质网络的一部分。
gamma-Aminobutyric acid (GABA)ergic neurons in the neocortex have been mainly regarded as interneurons and thought to provide local interactions. Recently, however, glutamate decarboxylase (GAD) immunocytochemistry combined with retrograde labeling experiments revealed the existence of GABAergic projection neurons in the neocortex. We further studied the network of GABAergic projection neurons in the neocortex by using GAD67-green fluorescent protein (GFP) knock-in mice for retrograde labeling and a novel neocortical GABAergic neuron labeling method for axon tracing. Many GFP-positive neurons were retrogradely labeled after Fast Blue injection into the primary somatosensory, motor and visual cortices. These neurons were labeled not only around the injection site, but also at a long distance from the injection site. Of the retrogradely labeled GABAergic neurons remote from the injection sites, the vast majority (91%) exhibited somatostatin immunoreactivity, and were preferentially distributed in layer II, layer VI and in the white matter. In addition, most of GABAergic projection neurons were positive for neuropeptide Y (82%) and neuronal nitric oxide synthase (71%). We confirmed the long-range projections by tracing GFP-labeled GABAergic neurons with axon branches traveled rostro-caudally and medio-laterally. Axon branches could be traced up to 2 mm. Some (n = 2 of 4) were shown to cross the areal boundaries. The GABAergic projection neurons preferentially received neocortical inputs. From these results, we conclude that GABAergic projection neurons are distributed throughout the neocortex and are part of a corticocortical network.