Involvement of the mGluR1 Receptor in Hippocampal Synaptic Plasticity and Associative Learning in Behaving Mice

• Published in: Cerebral cortex (New York, N.Y. 1991) Vol. 18; no. 7; pp. 1653 - 1663
• Main Authors: Gil-Sanz, Cristina, Delgado-García, José M., Fairén, Alfonso, Gruart, Agnès
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.07.2008; Oxford Publishing Limited (England)
• Subjects: Animals; Association Learning - physiology; BAY36-7620; Behavior, Animal - physiology; classical conditioning; hippocampus; Hippocampus - physiology; long-term potentiation; Male; mGluR1 receptor; Mice; Mice, Knockout; Neuronal Plasticity - physiology; Neurons - physiology; Receptors, Metabotropic Glutamate - genetics; Receptors, Metabotropic Glutamate - metabolism; synaptic plasticity; Synaptic Transmission - physiology; mGluR1 receptor; BAY36-7620; synaptic plasticity; classical conditioning; hippocampus; long-term potentiation
• ISSN: 1047-3211; 1460-2199
• DOI: 10.1093/cercor/bhm193

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.