Help Privacy Policy Disclaimer
  Advanced SearchBrowse




Journal Article

Cre-activation in ErbB4-positive neurons of floxed Grin1/NMDA receptor mice is not associated with major behavioral impairment


Sprengel,  Rolf
Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society;

Fulltext (restricted access)
There are currently no full texts shared for your IP range.
Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available

Mallien, A. S., Pfeiffer, N., Vogt, M. A., Chourbaji, S., Sprengel, R., Gass, P., et al. (2021). Cre-activation in ErbB4-positive neurons of floxed Grin1/NMDA receptor mice is not associated with major behavioral impairment. Frontiers in Psychiatry, 12: 750106, pp. 1-12. doi:10.3389/fpsyt.2021.750106.

Cite as: https://hdl.handle.net/21.11116/0000-0009-8855-E
Extensive evidence suggests a dysfunction of the glutamate NMDA receptor (NMDAR)
in schizophrenia, a severe psychiatric disorder with putative early neurodevelopmental origins, but clinical onset mainly during late adolescence. On the other hand, pharmacological models using NMDAR antagonists and the clinical manifestation of anti-NMDAR encephalitis indicate that NMDAR blockade/hypofunction can trigger psychosis also at adult stages, without any early developmental dysfunction. Previous genetic models of NMDAR hypofunction restricted to parvalbumin-positive interneurons indicate the necessity of an early postnatal impairment to trigger schizophrenialike
abnormalities, whereas the cellular substrates of NMDAR-mediated psychosis at
adolescent/adult stages are unknown. Neuregulin 1 (NRG1) and its receptor ErbB4
represent schizophrenia-associated susceptibility factors that closely interact with NMDAR. To determine the neuronal populations implicated in “late” NMDAR-driven psychosis, we analyzed the effect of the inducible ablation of NMDARs in ErbB4-
expressing cells in mice during late adolescence using a pharmacogenetic approach. Interestingly, the tamoxifen-inducible NMDAR deletion during this late developmental stage did not induce behavioral alterations resembling depression, schizophrenia or anxiety. Our data indicate that post-adolescent NMDAR deletion, even in a wider cell population than parvalbumin-positive interneurons, is also not sufficient to generate behavioral abnormalities resembling psychiatric disorders. Other neuronal substrates that have to be revealed by future studies, may underlie post-adolescent NMDAR-driven psychosis.