Brown Craig E, Seif Isabelle, De Maeyer Edward, Dyck Richard H
Department of Psychology, University of Calgary, 2500 University Drive, NW, Calgary, Alberta T2N 1N4, Canada.
Brain Res Dev Brain Res. 2003 Apr 14;142(1):19-29. doi: 10.1016/s0165-3806(03)00008-7.
Genetic inactivation of monoamine oxidase-A (MAO-A) significantly elevates levels of serotonin (5-HT) during early development and causes a disruption in the compartmented organization of thalamocortical axon terminals in layer 4 of the somatosensory cortex. In order to determine whether corticocortical innervation of the primary somatosensory cortex is also affected by this mutation, we examined the distribution of zinc-containing axon terminals (terminals known to originate from within the cortex) in the developing somatosensory cortex of MAO-A knockout mice, at postnatal days (PD) 3, 5, 6, 8, 10, 12, 15, 28, and 60. In layer 4 of wild-type mice, histochemical staining for zinc respected barrel-specific compartments at all ages beyond PD 5. By contrast, zinc staining in MAO-A knockout mice did not exhibit signs of barrel compartmentation at any age. Across cortical layers, substantial developmental changes in the distribution of zinc-containing terminals were observed in wild-type mice up until PD 12, at which time the mature lamina-specific pattern of zinc staining was achieved. Similar changes were observed in the somatosensory cortex of MAO-A knockout mice, except that its developmental time course was significantly compressed, with zincergic innervation achieving a mature appearance by PD 8. These results provide evidence that an excess of monoamines, most likely 5-HT, dramatically perturbs the columnar organization of intracortical zincergic afferents in layer 4 and significantly accelerates the appearance of a mature laminar pattern of zinc-containing corticocortical terminals.
单胺氧化酶A（MAO-A）的基因失活在早期发育过程中显著提高了血清素（5-HT）水平，并导致体感皮层第4层丘脑皮质轴突终末的分隔组织受到破坏。为了确定原发性体感皮层的皮质-皮质神经支配是否也受此突变影响，我们在出生后第3、5、6、8、10、12、15、28和60天，检查了MAO-A基因敲除小鼠发育中的体感皮层中含锌轴突终末（已知起源于皮层内的终末）的分布。在野生型小鼠的第4层，出生后第5天之后的所有年龄段，锌的组织化学染色都符合桶状特异性分隔。相比之下，MAO-A基因敲除小鼠的锌染色在任何年龄段都没有显示出桶状分隔的迹象。在野生型小鼠中，直到出生后第12天，含锌终末的分布在整个皮层各层都观察到了显著的发育变化，此时锌染色达到了成熟的层特异性模式。在MAO-A基因敲除小鼠的体感皮层中也观察到了类似的变化，只是其发育时间进程明显缩短，含锌神经支配在出生后第8天就达到了成熟外观。这些结果证明，过量的单胺，很可能是5-HT，极大地扰乱了第4层皮质内含锌传入纤维的柱状组织，并显著加速了含锌皮质-皮质终末成熟层状模式的出现。
