TY - JOUR
T1 - Neuronal Ig/Caspr Recognition Promotes the Formation of Axoaxonic Synapses in Mouse Spinal Cord
AU - Ashrafi, Soha
AU - Betley, J. Nicholas
AU - Comer, John D.
AU - Brenner-Morton, Susan
AU - Bar, Vered
AU - Shimoda, Yasushi
AU - Watanabe, Kazutada
AU - Peles, Elior
AU - Jessell, Thomas M.
AU - Kaltschmidt, Julia A.
N1 - National Institutes of Health (NIH) predoctoral training grant [527975]; Columbia University Neuroscience Fellowship; National Institute of General Medical Sciences of the NIH [T32GM007739]; Japan Society for the Promotion of Science [18300120]; NIH [NS50220, RO1 NS33245]; Israel Science Foundation; HHMI; Project ALS; Wellcome Trust; EU Framework Program 7; Memorial Sloan-Kettering start-up funds; Whitehall Foundation Research Grant; Louis V. Gerstner, Jr. Young Investigators AwardWe thank J. Sanes for generously providing antibodies, T. Sakurai for experimental help and helpful discussions, and N. Balaskas, A. Fink, S. Poliak, and S.-H. Shi for comments on the manuscript. We are grateful to K. Kridsada for technical assistance, D. Ng and J. Zhang for critical assistance with in situ hybridization, J. Bikoff for providing Ptf1a-derived cDNA, I. Horresh for checking antibodies to Caspr5, A. Todd for assistance with synaptic staining, D. Montag for CHL1 mutant tissue, and T. Cutforth for providing Kirrel-3 mutant mice. We thank Y. Zhang and J. Salzer for breeding Caspr mutant mice, S. Markx and J. Gogos for breeding Caspr2 mutant mice, T. Karayannis, E. Au, and G. Fishell for breeding Caspr4 mutant mice, D. Felsenfeld for breeding L1 mutant mice, and T. Sakurai and C. Mason for breeding NrCAM mutant mice. This work was supported by a National Institutes of Health (NIH) predoctoral training grant (527975) and a Columbia University Neuroscience Fellowship (J.N.B.), a Medical Scientist Training Program (MSTP) grant from the National Institute of General Medical Sciences of the NIH under award number T32GM007739 to the Weill Cornell/Rockefeller/Sloan-Kettering Tri-Institutional MD-PhD Program (J.D.C.), a Grant-in-Aid for Scientific Research (B) (#18300120) from the Japan Society for the Promotion of Science (Y.S. and K.W.), NIH grant NS50220 and the Israel Science Foundation (E.P.), HHMI, Project ALS, The Wellcome Trust, EU Framework Program 7, and NIH RO1 NS33245 (
PY - 2014/1/8
Y1 - 2014/1/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84891809781&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2013.10.060
DO - 10.1016/j.neuron.2013.10.060
M3 - مقالة
SN - 0896-6273
VL - 81
SP - 120
EP - 129
JO - Neuron
JF - Neuron
IS - 1
ER -