Involvement of the mGluR1 receptor in hippocampal synaptic plasticity and associative learning in behaving mice.
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.
Gil-Sanz
Cristina
C
Instituto de Neurociencias de Alicante, CSIC and Universidad Miguel Hernández, E-03550 San Juan de Alicante, Spain.
Delgado-García
José M
JM
Fairén
Alfonso
A
Gruart
Agnès
A
D000818:Animals; D001245:Association Learning / Q000502:physiology*; D001522:Behavior, Animal / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*
D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1