DOI: 10.1073/pnas.0308626100. Postsynaptic <i>N</i> -methyl- <scp>d</scp> -aspartate receptor function requires α-neurexins

Postsynaptic N -methyl- d -aspartate receptor function requires α-neurexins

10.1073/pnas.0308626100

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

α-Neurexins are neuron-specific cell-surface molecules that are essential for the functional organization of presynaptic Ca 2+ channels and release sites. We have now examined postsynaptic glutamate receptor function in α-neurexin knockout (KO) mice by using whole-cell recordings in cultured neocortical slices. Unexpectedly, we find that α-neurexins are required for normal activity of N -methyl- d -aspartate (NMDA)- but not α-amino-3-hydroxy-5-methyl-4-isoxyzolepropionic acid (AMPA)-type glutamate receptors. In α-neurexin-deficient mice, the ratio of NMDA- to AMPA-receptor currents, recorded as evoked synaptic responses, was diminished ≈50%. Furthermore, the NMDA-receptor-dependent component of spontaneous synaptic miniature responses was reduced ≈50%, whereas the AMPA-receptor-dependent component was unaffected. No alterations in the levels of NMDA- or AMPA-receptor proteins were detected. These results suggest that α-neurexins are required to maintain normal postsynaptic NMDA-receptor function. The decrease in NMDA-receptor activity in α-neurexin-deficient synapses could be due to a transsynaptic effect on the postsynaptic neuron (i.e., α-neurexins on the presynaptic inputs guide postsynaptic NMDA-receptor function) or to a cell-autonomous postsynaptic effect of α-neurexins on NMDA-receptor activity. To distinguish between these two possibilities, we cocultured WT GFP-labeled neurons with neocortical slices from α-neurexin-deficient or control mice. No difference was found between WT neurons innervated by inputs that contained or lacked α-neurexins, indicating that the absence of presynaptic α-neurexins alone does not depress postsynaptic NMDA-receptor function. Our data suggest that, in addition to the previously described presynaptic impairments, loss of α-neurexins induces postsynaptic changes by a cell-autonomous mechanism.

Bibliography

Kattenstroth, G., Tantalaki, E., SÃ¼dhof, T. C., Gottmann, K., & Missler, M. (2004). Postsynaptic N -methyl- d -aspartate receptor function requires Î±-neurexins. Proceedings of the National Academy of Sciences, 101(8), 2607â2612.

Authors 5

Gunnar Kattenstroth (first)
Evangelia Tantalaki (additional)
Thomas C. Südhof (additional)
Kurt Gottmann (additional)
Markus Missler (additional)

References 33 Referenced 84

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Dates

Type	When
Created	21 years, 6 months ago (Feb. 24, 2004, 11:03 p.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 8:57 a.m.)
Indexed	3 months, 1 week ago (May 21, 2025, 12:27 a.m.)
Issued	21 years, 6 months ago (Feb. 13, 2004)
Published	21 years, 6 months ago (Feb. 13, 2004)
Published Online	21 years, 6 months ago (Feb. 13, 2004)
Published Print	21 years, 6 months ago (Feb. 24, 2004)

Funders 0

None

BibTeX

@article{Kattenstroth_2004, title={Postsynaptic N -methyl- <scp>d</scp> -aspartate receptor function requires α-neurexins}, volume={101}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0308626100}, DOI={10.1073/pnas.0308626100}, number={8}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Kattenstroth, Gunnar and Tantalaki, Evangelia and Südhof, Thomas C. and Gottmann, Kurt and Missler, Markus}, year={2004}, month=feb, pages={2607–2612} }

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