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Absence of Whisker-Related Pattern Formation in Mice with NMDA Receptors Lacking Coincidence Detection Properties and Calcium Signaling

Rudhard, York, Kneussel, Matthias, Nassar, Mohammed A., Rast, Georg F., Annala, Alexander J., Chen, Philip E., Tigaret, Cezar M. ORCID: https://orcid.org/0000-0001-5848-6697, Dean, Isabel, Roes, Juergen, Gibb, Alasdair J., Hunt, Stephen P. and Schoepfer, Ralf 2003. Absence of Whisker-Related Pattern Formation in Mice with NMDA Receptors Lacking Coincidence Detection Properties and Calcium Signaling. Journal of Neuroscience 23 (6) , pp. 2323-2332. 10.1523/JNEUROSCI.23-06-02323.2003

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Neuroscience and Mental Health Research Institute (NMHRI)
Publisher: Society for Neuroscience
ISSN: 0270-6474
Date of First Compliant Deposit: 14 January 2020
Date of Acceptance: 16 December 2002
Last Modified: 03 May 2023 18:27
URI: https://orca.cardiff.ac.uk/id/eprint/128529

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