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Absence of whisker-related pattern formation in mice with NMDA receptors lacking coincidence detection properties and calcium signaling

Rudhard, Y; Kneussel, M; Nassar, MA; Rast, GF; Annala, AJ; Chen, PE; Tigaret, CM; ... Schoepfer, R; + view all (2003) Absence of whisker-related pattern formation in mice with NMDA receptors lacking coincidence detection properties and calcium signaling. J NEUROSCI , 23 (6) 2323 - 2332. Green open access

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Abstract

Precise refinement of synaptic connectivity is the result of activity-dependent mechanisms in which coincidence-dependent calcium signaling by NMDA receptors (NMDARs) under control of the voltage-dependent Mg2+ block might play a special role.In the developing rodent trigeminal system, the pattern of synaptic connections between whisker-specific inputs and their target cells in the brainstem is refined to form functionally and morphologically distinct units (barrelettes). To test the role of NMDA receptor signaling in this process, we introduced the N598R mutation into the native NR1 gene. This leads to the expression of functional NMDARs that are Mg2+ insensitive and Ca2+ impermeable.Newborn mice expressing exclusively NR1 N598R-containing NMDARs do not show any whisker-related patterning in the brainstem, whereas the topographic projection of trigeminal afferents and gross brain morphology appear normal. Furthermore, the NR1 N598R mutation does not affect expression levels of NMDAR subunits and other important neurotransmitter receptors.Our results show that coincidence detection by, and/or Ca2+ permeability of, NMDARs is necessary for the development of somatotopic maps in the brainstem and suggest that highly specific signaling underlies synaptic refinement.

Type: Article
Title: Absence of whisker-related pattern formation in mice with NMDA receptors lacking coincidence detection properties and calcium signaling
Identifier: PMID: 12657691
Open access status: An open access version is available from UCL Discovery
Keywords: barrelette, somatosensory, whisker, trigeminal pathway, pattern formation, topographic map, NMDA receptor, NMDAR, coincidence detection, point mutation, knock-in, homologous recombination, cytochrome oxidase, DiI labeling, Mg2+ block, Ca2+-dependent signaling, brainstem, Cre recombinase, loxP, Tenascin, boundary, D-ASPARTATE RECEPTOR, SOMATOSENSORY CORTEX, NEURONAL MIGRATION, CYTOCHROME-OXIDASE, KNOCKOUT MICE, SUBUNIT, MOUSE, CHANNEL, BRAIN, ORGANIZATION
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > The Ear Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: http://discovery.ucl.ac.uk/id/eprint/8328
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