Regulation of synaptic plasticity by mGluR1 studied in vivo in mGluR1 mutant mice.
The role of the metabotropic glutamate receptor 1 (mGluR1) in synaptic plasticity was investigated in vivo in the intact hippocampus of mutant mice lacking this receptor. In a previous study we showed reduced long-term potentiation (LTP) in the dentate gyrus of mGluR1 -/- mice in vivo, but not when LTP was studied in a slice preparation. A possible explanation of this difference is that dentate neurons receive more inhibitory synaptic drive in vivo than in slice preparation where many inhibitory axon collaterals are lost. We report here that another form of synaptic plasticity, paired-pulse depression of the population spike, is also abnormal in the dentate gyrus of mGluR1-deficient mice when tested in vivo. In wild-type mice, stimulation of the medial perforant path produced paired-pulse depression of inter-pulse intervals (IPIs) up to 30 ms. Mutant mGluR1, on the other hand, showed a significantly longer IPI depression, up to 50 ms. Paired-pulse depression results from the activation of inhibitory interneurons. The GABA(B) agonist baclofen, acting presynaptically on the GABA interneurons, attenuated paired-pulse depression and allowed for a normal and stable LTP in mGluR1 mutant mice. These findings suggest an indirect role for mGluR1 in synaptic plasticity via a regulation of GABA inhibition.
Bordi
F
F
Department of Pharmacology, Glaxo-Wellcome Medicines Research Centre, Verona, Italy. fb23261@ggr.co.uk
Reggiani
A
A
Conquet
F
F
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D017660:Autoreceptors / Q000502:physiology; D001418:Baclofen / Q000494:pharmacology; D018891:Dentate Gyrus / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D004558:Electric Stimulation; D004594:Electrophysiology; D018755:GABA Agonists / Q000494:pharmacology; D058786:GABA-B Receptor Agonists; D007395:Interneurons / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D017774:Long-Term Potentiation / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016296:Mutagenesis / Q000502:physiology; D009433:Neural Inhibition / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics* / Q000378:metabolism
D017660:Autoreceptors; D018755:GABA Agonists; D058786:GABA-B Receptor Agonists; D018094:Receptors, Metabotropic Glutamate; D001418:Baclofen