Zhenping Jia*, You-Ming Lu*,Jeffrey T. Henderson*, Franco Taverna*, Carmelo Romano#,
Wanda Abramow-Newerly*, J. Martin Wojtowicz!,and John C. Roder*
* Samuel Lunenfeld Research Institute, Mount SinaiHospital,
Program and Development and FetalHealth, 600 University Ave., Toronto, Ontario M5G-1X5
# Department of Anatomy and Neurobiology, WashingtonUniversity, St. Louis, Missouri
! Department of Physiology, Universityof Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8
Learning and Memory, 5, 331-343, 1998
Abstract
Long term potentiation (LTP) of glutaminergic synapses has been suggested as a substrate for learning and memory, but the involvement of G-protein linked metabotrophic glutamate receptors is controversial. Therefore, we created mutant mice which expressed no mGluR5, but showed normal development. Whole-cell patch-clamp recordings of evoked excitatory postsynaptic currents (EPSC's) in CA1 pyramidal neurons from control hippocampus following tetanus, revealed equal enhancementof the AMPA and NMDA receptor-mediated components. In contrast, CA1 neurons from mGluR5-deficient mice showed a complete loss of the NMDA receptor-mediated component of LTP, but normal LTP of the AMPA receptor-mediated component.A similar selective deficit in NMDA receptor-mediated LTP was found in wild-type neurons treated with 25 uM PKCI-19-36, an inhibitor of proteinkinase C (PKC). Furthermore, the LTP deficit in mGluR5 mutant mice couldbe rescued by stimulating PKC. These results suggest that post-synapticmGluR5 may be coupled to the NMDA receptor potentiation via PKC, and that this signaling mechanism is distinct for AMPA receptor-mediated LTP. These findings provide the first evidence for the involvement of mGluR5 in NMDA receptor-mediated LTP, and strongly support the hypothesis that AMPA and NMDA expression mechanisms for LTP are distinct.
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