title: Neuronal Ig/Caspr recognition promotes the formation of axoaxonic synapses in mouse spinal cord.
abstract: 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.
authors.affiliation: Neuroscience Program, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA; Developmental Biology Program, Sloan-Kettering Institute, New York, NY 10065, USA.
authors.forename: Soha
authors.initials: S
authors.lastname: Ashrafi
authors.affiliation: Howard Hughes Medical Institute, Kavli Institute of Brain Science, Departments of Neuroscience, Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
authors.forename: J Nicholas
authors.initials: JN
authors.lastname: Betley
authors.affiliation: Neuroscience Program, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA; Developmental Biology Program, Sloan-Kettering Institute, New York, NY 10065, USA; Weill Cornell/Rockefeller/Sloan-Kettering Tri-Institutional MD-PhD Program, New York, NY 10065, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Comer
authors.affiliation: Howard Hughes Medical Institute, Kavli Institute of Brain Science, Departments of Neuroscience, Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Brenner-Morton
authors.affiliation: Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Vered
authors.initials: V
authors.lastname: Bar
authors.affiliation: Department of Bioengineering, Nagaoka University of Technology, 1603-1, Kamitomiokamachi, Nagaoka, Niigata 940-2188, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Shimoda
authors.affiliation: Department of Bioengineering, Nagaoka University of Technology, 1603-1, Kamitomiokamachi, Nagaoka, Niigata 940-2188, Japan; Nagaoka National College of Technology, 888, Nishikatakaimachi, Nagaoka, Niigata 940-8532, Japan.
authors.forename: Kazutada
authors.initials: K
authors.lastname: Watanabe
authors.affiliation: Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Elior
authors.initials: E
authors.lastname: Peles
authors.affiliation: Howard Hughes Medical Institute, Kavli Institute of Brain Science, Departments of Neuroscience, Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA. Electronic address: tmj1@columbia.edu.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Jessell
authors.affiliation: Neuroscience Program, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA; Developmental Biology Program, Sloan-Kettering Institute, New York, NY 10065, USA. Electronic address: kaltschj@mskcc.org.
authors.forename: Julia A
authors.initials: JA
authors.lastname: Kaltschmidt
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D019295:Computational Biology; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008959:Models, Neurological; D009154:Mutation / Q000235:genetics; D010320:Parvalbumins / Q000235:genetics / Q000378:metabolism; D017729:Presynaptic Terminals / Q000502:physiology*; D011984:Sensory Receptor Cells / Q000145:classification / Q000166:cytology* / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology*; D013569:Synapses / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; C491322:Cntnap1 protein, mouse; C474214:Kirrel3 protein, mouse; D008164:Luminescent Proteins; D008565:Membrane Proteins; C545358:NB-2 protein, mouse; D010320:Parvalbumins; D014157:Transcription Factors; C062602:transcription factor PTF1