Forebrain-specific glutamate receptor B deletion impairs spatial memory but not hippocampal field long-term potentiation.
We demonstrate the fundamental importance of glutamate receptor B (GluR-B) containing AMPA receptors in hippocampal function by analyzing mice with conditional GluR-B deficiency in postnatal forebrain principal neurons (GluR-B(deltaFb)). These mice are as adults sufficiently robust to permit comparative cellular, physiological, and behavioral studies. GluR-B loss induced moderate long-term changes in the hippocampus of GluR-B(deltaFb) mice. Parvalbumin-expressing interneurons in the dentate gyrus and the pyramidal cells in CA3 were decreased in number, and neurogenesis in the subgranular zone was diminished. Excitatory synaptic CA3-to-CA1 transmission was reduced, although synaptic excitability, as quantified by the lowered threshold for population spike initiation, was increased compared with control mice. These changes did not alter CA3-to-CA1 long-term potentiation (LTP), which in magnitude was similar to LTP in control mice. The altered hippocampal circuitry, however, affected spatial learning in GluR-B(deltaFb) mice. The primary source for the observed changes is most likely the AMPA receptor-mediated Ca2+ signaling that appears after GluR-B depletion, because we observed similar alterations in GluR-B(QFb) mice in which the expression of Ca2+-permeable AMPA receptors in principal neurons was induced by postnatal activation of a Q/R-site editing-deficient GluR-B allele.
Shimshek
Derya R
DR
Department of Molecular Neurobiology, Max Planck Institute for Medical Research, D-69120 Heidelberg, Germany.
Jensen
Vidar
V
Celikel
Tansu
T
Geng
Yu
Y
Schupp
Bettina
B
Bus
Thorsten
T
Mack
Volker
V
Marx
Verena
V
Hvalby
Øivind
Ø
Seeburg
Peter H
PH
Sprengel
Rolf
R
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002455:Cell Division; D018891:Dentate Gyrus / Q000166:cytology / Q000378:metabolism; D005106:Exploratory Behavior; D020868:Gene Silencing; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology*; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009473:Neuronal Plasticity; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D016548:Prosencephalon / Q000378:metabolism*; D018091:Receptors, AMPA / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013028:Space Perception / Q000502:physiology*; D009435:Synaptic Transmission
D018091:Receptors, AMPA; C115953:glutamate receptor type B; D002118:Calcium