Rudhard, Y.;
Kneussel, M.;
Nassar, M.A.;
Rast, G.F.;
Annala, A.J.;
Chen, P.E.;
Tigaret, C.M.;
... Schoepfer, R.; + view all
(2003)
Absence of Whisker-related pattern formation in mice with NMDA receptors lacking coincidence detection properties and calcium signaling.
The Journal of Neuroscience
, 23
(6)
pp. 2323-2332.
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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 |
| Publisher version: | http://www.jneurosci.org/cgi/content/abstract/23/6... |
| Language: | English |
| Additional information: | Published by the Society of Neuroscience This work is licensed under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. The license allows you to copy, distribute, and transmit the work, as well as adapting it. However, you must attribute the work to the author (but not in any way that suggests that they endorse you or your use of the work), and cannot use the work for commercial purposes without prior permission of the author. If you alter or build upon this work, you can distribute the resulting work only under the same or similar license to this one. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/ or send a letter to Creative Commons, 444 Castro Street, Suite 900, Mountain View, California, 94041, USA. |
| 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 |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/9746 |
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