title: Distinct circuit-dependent functions of presynaptic neurexin-3 at GABAergic and glutamatergic synapses.
abstract: α- and β-neurexins are presynaptic cell-adhesion molecules whose general importance for synaptic transmission is well documented. The specific functions of neurexins, however, remain largely unknown because no conditional neurexin knockouts are available and targeting all α- and β-neurexins produced by a particular gene is challenging. Using newly generated constitutive and conditional knockout mice that target all neurexin-3α and neurexin-3β isoforms, we found that neurexin-3 was differentially required for distinct synaptic functions in different brain regions. Specifically, we found that, in cultured neurons and acute slices of the hippocampus, extracellular sequences of presynaptic neurexin-3 mediated trans-synaptic regulation of postsynaptic AMPA receptors. In cultured neurons and acute slices of the olfactory bulb, however, intracellular sequences of presynaptic neurexin-3 were selectively required for GABA release. Thus, our data indicate that neurexin-3 performs distinct essential pre- or postsynaptic functions in different brain regions by distinct mechanisms.
authors.affiliation: Department of Molecular and Cellular Physiology, Stanford University Medical School, Stanford, California, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Aoto
authors.affiliation: Department of Molecular and Cellular Physiology, Stanford University Medical School, Stanford, California, USA.
authors.forename: Csaba
authors.initials: C
authors.lastname: Földy
authors.affiliation: Department of Molecular and Cellular Physiology, Stanford University Medical School, Stanford, California, USA.
authors.forename: Silviana Maria Ciurea
authors.initials: SM
authors.lastname: Ilcus
authors.affiliation: 1] Department of Molecular and Cellular Physiology, Stanford University Medical School, Stanford, California, USA. [2] Howard Hughes Medical Institute, Stanford University Medical School, Stanford, California, USA. [3] Division of Cerebral Structure, Department of Cerebral Research, National Institute for Physiological Sciences, Okazaki, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Tabuchi
authors.affiliation: 1] Department of Molecular and Cellular Physiology, Stanford University Medical School, Stanford, California, USA. [2] Howard Hughes Medical Institute, Stanford University Medical School, Stanford, California, USA.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Südhof
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D009830:Olfactory Bulb / Q000166:cytology / Q000378:metabolism*; D018091:Receptors, AMPA / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; C583456:neurexin 3, mouse; D005680:gamma-Aminobutyric Acid