Involvement of the mGluR1 receptor in hippocampal synaptic plasticity and associative learning in behaving mice

Cereb Cortex. 2008 Jul;18(7):1653-63. doi: 10.1093/cercor/bhm193. Epub 2007 Nov 17.


Metabotropic glutamate receptor 1 (mGluR1) has been related to processes underlying learning in hippocampal circuits, but demonstrating its involvement in synaptic plasticity when measured directly on the relevant circuit of a learning animal has proved to be technically difficult. We have recorded the functional changes taking place at the hippocampal CA3-CA1 synapse during the acquisition of an associative task in conscious mice carrying a targeted disruption of the mGluR1 gene. Animals were classically conditioned to evoke eyelid responses, using a trace (conditioned stimulus [CS], tone; unconditioned stimulus [US], electric shock) paradigm. Acquisition of this task was impaired in mutant mGluR1(+/-) mice and abolished in mGluR1(-/-) mice. A single pulse presented to Schaffer collaterals during the CS-US interval evoked a monosynaptic field excitatory postsynaptic potential at ipsilateral CA1 pyramidal cells, whose slope was linearly related to learning evolution in controls but not in mGluR1 mutants. Long-term potentiation evoked by train stimulation of Schaffer collaterals was also impaired in both mGluR1(+/-) and mGluR1(-/-) animals. Administration of the selective mGluR1 antagonist (3aS,6aS)-6a-naphthalen-2-ylmethyl-5-methyliden-hexahydro-cyclopental [c]furan-1-on to wild-type animals mimicked the functional changes associated to mGluR1 insufficiency in mutants. Thus, mGluR1 is required for activity-dependent synaptic plasticity and associative learning in behaving mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Association Learning / physiology*
  • Behavior, Animal / physiology*
  • Hippocampus / physiology*
  • Male
  • Mice
  • Mice, Knockout
  • Neuronal Plasticity / physiology*
  • Neurons / physiology*
  • Receptors, Metabotropic Glutamate / genetics
  • Receptors, Metabotropic Glutamate / metabolism*
  • Synaptic Transmission / physiology*


  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor type 1