Aberrant development of hippocampal circuits and altered neural activity in netrin 1-deficient mice.
Aberrant development of hippocampal circuits and altered neural activity in netrin 1-deficient mice.
复制标题
netrin 1 缺陷小鼠的海马回路发育异常和神经活动改变。
作者：
M. Barallobre;J. D. Río;Soledad Alcántara;Víctor Borrell;Fernando Aguado;M. Ruiz;Margarita Carmona;M. Martín;M. Fabre;Rafael Yuste;Marc Tessier;Eduardo Soriano
扩散因子，包括netrins和semaphorins，被认为是前脑神经回路形成的重要线索。在这里，我们研究了netrin 1在海马连接发育中的作用。我们发现，netrin 1和它的受体，DCC，分别在发展中的海马伞和投射神经元中表达，netrin 1通过DCC受体促进体外海马轴突的生长。我们还表明，netrin 1缺陷小鼠的海马显示了纤维束和寻路错误的错误取向，如针对表面蛋白TAG-1，L1和DCC的抗体所检测到的。DiI注射表明，海马连合轴突不跨越这些突变体的中线。相反，当轴突接近中线时，它们转向腹侧并形成一个巨大的异常投射到同侧隔。此外，netrin 1缺陷小鼠的同侧内鼻-海马和CA 3-至-CA 1关联投射均显示改变的层特异性终止模式。最后，用Ca（2+）指示剂Fura 2-AM进行的光学记录显示，netrin 1突变小鼠的隔中自发神经元活动减少。我们的结论是netrin 1不仅需要在前脑交叉连接的形成，但也为适当的层特定的同侧预测和控制正常水平的自发神经活动的目标。
Diffusible factors, including netrins and semaphorins, are believed to be important cues for the formation of neural circuits in the forebrain. Here we have examined the role of netrin 1 in the development of hippocampal connections. We show that netrin 1 and its receptor, Dcc, are expressed in the developing fimbria and in projection neurons, respectively, and that netrin 1 promotes the outgrowth of hippocampal axons in vitro via DCC receptors. We also show that the hippocampus of netrin 1-deficient mice shows a misorientation of fiber tracts and pathfinding errors, as detected with antibodies against the surface proteins TAG-1, L1 and DCC. DiI injections show that hippocampal commissural axons do not cross the midline in these mutants. Instead, when axons approach the midline, they turn ventrally and form a massive aberrant projection to the ipsilateral septum. In addition, both the ipsilateral entorhino-hippocampal and the CA3-to-CA1 associational projections show an altered pattern of layer-specific termination in netrin 1-deficient mice. Finally, optical recordings with the Ca(2+) indicator Fura 2-AM show that spontaneous neuronal activity is reduced in the septum of netrin 1-mutant mice. We conclude that netrin 1 is required not only for the formation of crossed connections in the forebrain, but also for the appropriate layer-specific targeting of ipsilateral projections and for the control of normal levels of spontaneous neural activity.
影响因子：
56.9
作者：
Polleux, F;Giger, RJ;Ghosh, A
通讯作者：
Ghosh, A
影响因子：
2.7
作者：
Yuan, WL;Zhou, LJ;Ornitz, DM
通讯作者：
Ornitz, DM