Neuronal Ig/Caspr Recognition Promotes the Formation of Axoaxonic Synapses in Mouse Spinal Cord

被引:65
作者
Ashrafi, Soha [1 ,2 ]
Betley, J. Nicholas [3 ,4 ,5 ]
Comer, John D. [1 ,2 ,6 ]
Brenner-Morton, Susan [3 ,4 ,5 ]
Bar, Vered [7 ]
Shimoda, Yasushi [8 ]
Watanabe, Kazutada [8 ,9 ]
Peles, Elior [7 ]
Jessell, Thomas M. [3 ,4 ,5 ]
Kaltschmidt, Julia A. [1 ,2 ]
机构
[1] Weill Cornell Grad Sch Med Sci, Neurosci Program, New York, NY 10065 USA
[2] Sloan Kettering Inst, Dev Biol Program, New York, NY 10065 USA
[3] Columbia Univ, Howard Hughes Med Inst, Kavli Inst Brain Sci, Dept Neurosci, New York, NY 10032 USA
[4] Columbia Univ, Howard Hughes Med Inst, Kavli Inst Brain Sci, Dept Biochem, New York, NY 10032 USA
[5] Columbia Univ, Howard Hughes Med Inst, Kavli Inst Brain Sci, Dept Mol Biophys, New York, NY 10032 USA
[6] Weill Cornell Rockefeller Sloan Kettering Triinst, New York, NY 10065 USA
[7] Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel
[8] Nagaoka Univ Technol, Dept Bioengn, Nagaoka, Niigata 9402188, Japan
[9] Nagaoka Natl Coll Technol, Nagaoka, Niigata 9408532, Japan
基金
美国国家卫生研究院; 日本学术振兴会; 以色列科学基金会; 英国惠康基金;
关键词
IMMUNOGLOBULIN SUPERFAMILY; MYELINATED AXONS; DIFFERENTIAL EXPRESSION; ADHESION MOLECULES; MICE DEFICIENT; MEMBER; TAG-1; SPECIFICITY; CASPR2; CONTACTIN;
D O I
10.1016/j.neuron.2013.10.060
中图分类号
Q189 [神经科学];
学科分类号
071006 [神经生物学];
摘要
Inhibitory microcircuits are wired with a precision that underlies their complex regulatory roles in neural information processing. In the spinal cord, one specialized class of GABAergic interneurons (GABApre) mediates presynaptic inhibitory control of sensory-motor synapses. The synaptic targeting of these GABAergic neurons exhibits an absolute dependence on proprioceptive sensory terminals, yet the molecular underpinnings of this specialized axoaxonic organization remain unclear. Here, we show that sensory expression of an NB2 (Contactin5)/Caspr4 coreceptor complex, together with spinal interneuron expression of NrCAM/CHL1, directs the high-density accumulation of GABAergic boutons on sensory terminals. Moreover, genetic elimination of NB2 results in a disproportionate stripping of inhibitory boutons from high-density GABApre-sensory synapses, suggesting that the preterminal axons of GABApre neurons compete for access to individual sensory terminals. Our findings define a recognition complex that contributes to the assembly and organization of a specialized GABAergic microcircuit.
引用
收藏
页码:120 / 129
页数:10
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