Walling Susan G, Brown Robert A, Miyasaka Nobuhiko, Yoshihara Yoshihiro, Harley Carolyn W
Department of Psychology, Memorial University of Newfoundland, St. John's NL, Canada.
Front Behav Neurosci. 2012 May 28;6:23. doi: 10.3389/fnbeh.2012.00023. eCollection 2012.
We generated transgenic mice in which a trans-synaptic tracer, wheat germ agglutinin (WGA), was specifically expressed in the locus coeruleus (LC) neurons under the control of the dopamine-β-hydroxylase (DBH) gene promoter. WGA protein was produced in more than 95% of the tyrosine hydroxylase (TH)-positive LC neurons sampled. Transynaptic transfer of WGA was most evident in CA3 neurons of the hippocampus, but appeared absent in CA1 neurons. Faint but significant WGA immunoreactivity was observed surrounding the nuclei of dentate granule cells. Putative hilar mossy cells, identified by the presence of calretinin in the ventral hippocampus, appeared uniformly positive for transynaptically transferred WGA protein. GAD67-positive interneurons in the hilar and CA3 regions tended to be WGA-positive, although a subset of them did not show WGA co-localization. The same mixed WGA uptake profile was apparent when examining co-localization with parvalbumin. The selective uptake of WGA by dentate granule cells, mossy cells, and CA3 pyramidal neurons is consistent with evidence for a large proportion of conventional synapses adjacent to LC axonal varicosities in these regions. The lack of WGA uptake in the CA1 region and its relatively sparse innervation by DBH-positive fibers suggest that a majority of the TH-positive classical synapses revealed by electron microscopy in that region may be producing dopamine. The overall pattern of WGA uptake in these transgenic mice implies a selective role for the granule cell-mossy cell-CA3 network in processing novelty or the salient environmental contingency changes signaled by LC activity.
我们构建了转基因小鼠，其中在多巴胺-β-羟化酶（DBH）基因启动子的控制下，跨突触示踪剂小麦胚凝集素（WGA）在蓝斑（LC）神经元中特异性表达。在采样的超过95%的酪氨酸羟化酶（TH）阳性LC神经元中产生了WGA蛋白。WGA的跨突触转移在海马体的CA3神经元中最为明显，但在CA1神经元中似乎不存在。在齿状颗粒细胞核周围观察到微弱但显著的WGA免疫反应性。通过腹侧海马体中钙视网膜蛋白的存在鉴定的假定门区苔藓细胞，对跨突触转移的WGA蛋白呈现一致的阳性反应。门区和CA3区的GAD67阳性中间神经元倾向于WGA阳性，尽管其中一部分没有显示WGA共定位。在检查与小白蛋白的共定位时，同样的混合WGA摄取模式很明显。齿状颗粒细胞、苔藓细胞和CA3锥体神经元对WGA的选择性摄取与这些区域中与LC轴突膨体相邻的大部分传统突触的证据一致。CA1区缺乏WGA摄取及其被DBH阳性纤维相对稀疏的支配表明，该区域电子显微镜显示的大多数TH阳性经典突触可能在产生多巴胺。这些转基因小鼠中WGA摄取的总体模式意味着颗粒细胞-苔藓细胞-CA3网络在处理新奇性或由LC活动发出信号的显著环境意外变化中具有选择性作用。
