title: Opposing role of NMDA receptor GluN2B and GluN2D in somatosensory development and maturation.
abstract: Development of correct topographical connections between peripheral receptors and central somatosensory stations requires activity-dependent synapse refinement, in which the NMDA type of glutamate receptors plays a key role. Here we compared functional roles of GluN2B (GluRε2 or NR2B) and GluN2D (GluRε4 or NR2D), two major regulatory subunits of neonatal NMDA receptors, in development of whisker-related patterning at trigeminal relay stations. Compared with control littermates, both the appearance of whisker-related patterning and the termination of the critical period, as assessed by unilateral infraorbital nerve transection, were delayed by nearly a day in the somatosensory cortex of GluN2B(+/-) mice but advanced by nearly a day in GluN2D(-/-) mice. Similar temporal shifts were found at subcortical relay stations in the thalamus and brainstem of GluN2B(+/-) and GluN2D(-/-) mice. In comparison, the magnitude of lesion-induced critical period plasticity in the somatosensory cortex, as assessed following row-C whisker removal, was normal in both mutants. Thus, GluN2B and GluN2D play counteractive roles in temporal development and maturation of somatosensory maps without affecting the magnitude of critical period plasticity. To understand the opposing action, we then examined neuronal and synaptic expressions of the two subunits along the trigeminal pathway. At each trigeminal station, GluN2B was predominant at asymmetrical synapses of non-GABAergic neurons, whereas GluN2D was selective to asymmetrical synapses of GABAergic neurons. Together, our findings suggest that GluN2B expressed at glutamatergic synapses on glutamatergic projection neurons facilitates refinement of ascending pathway synapses directly, whereas GluN2D expressed at glutamatergic synapses on GABAergic interneurons delays it indirectly.
authors.affiliation: Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Miwako
authors.initials: M
authors.lastname: Yamasaki
authors.affiliation: Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Rieko
authors.initials: R
authors.lastname: Okada
authors.affiliation: Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan, Department of Pediatric Dentistry, Hokkaido University Graduate School of Dental Medicine, Sapporo 060-8586, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Takasaki
authors.affiliation: Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Shima
authors.initials: S
authors.lastname: Toki
authors.affiliation: Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan, Department of Anatomy, Kitasato University School of Medicine, Sagamihara, Kanagawa 252-0374, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fukaya
authors.affiliation: Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Natsume
authors.affiliation: Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sakimura
authors.affiliation: Brain Science Laboratory, The Research Organization of Science and Technology, Ritsumeikan University, Shiga 525-8577, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Mishina
authors.affiliation: Department of Pediatric Dentistry, Nihon University School of Dentistry, Tokyo 101-8310, Japan, and.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Shirakawa
authors.affiliation: Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan, Japan Science and Technology Agency, CREST, Sanbancho, Tokyo 102-0075, Japan watamasa@med.hokudai.ac.jp.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D019521:Body Patterning / Q000502:physiology; D001931:Brain Mapping; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055495:Neurogenesis / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013003:Somatosensory Cortex / Q000254:growth & development* / Q000378:metabolism; D014738:Vibrissae / Q000294:innervation
chemical_list: C121001:NR2B NMDA receptor; C464436:NR2D NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate
keywords: GluN2B; GluN2D; NMDA receptor; barrel; critical period; somatosensory