You-Ming Lu!, Zhengping Jia*, Christopher Janus*,Jeffrey T. Henderson*,
Robert Gerlai*, J. Martin Wojtowicz!, andJohn C. Roder*
* Samuel Lunenfeld Research Institute, Mount SinaiHospital,
Program and Development and FetalHealth, 600 University Ave., Toronto, Ontario M5G-1X5
! Department of Physiology, Universityof Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8
Journal of Neuroscience, 17(13),pp. 5196-5205, 1997
Abstract
Metabotropic glutamate receptor have been postulate to play a role in long-term potentiation (LTP), learningand memory. In order to test this hypothesis we have recently generated mutant mice which express no mGluR5, but normal levels of other glutamate receptors. Serial sections through the CNS revealed normal development of gross anatomical features. These mutant mice appeared healthy and showed no signs of sensory or motor deficits, but were impaired in the acquisition and utilization of spatial information in both the Morris water maze and contextual information in the fear conditioning test. NMDA-R-dependent LTP in mGluR5 mutants was significantly reduced in the CA1 region and dentate gyrus of the hippocampus, whereas NMDA-R-independent LTP remained intact in the mossy fibre pathway of the CA3 region. The reduction in NMDA-dependent synaptic currents, in the mutants, may underlie the reduced LTP. We propose that mGluR5 plays a key regulatory role in NMDA-R dependent LTP. The results show that mGluR5 may be the major ACPD receptor involved in synaptic depressionin CA1, but not dentate gyrus, where mGluR1 might compensate. Since LTP was also deficient in the dentate gyrus, this depressant effect of mGluR5 is not related to the reduced LTP. In addition, other measures of presynaptic function, such as paired pulse facilitation and PTP in CA1, were normal,which suggests that the decline in LTP in mGluR5 mutants may be a postsynaptic effect.
HendersonLaboratory Home Page
Send mail to Dr. Henderson:.jeff.henderson@utoronto.ca