Modulation of GABAergic inhibition in the rat superior colliculus by a presynaptic group II metabotropic glutamate receptor.
Previous work has indicated that metabotropic glutamate receptors (mGluRs) modulate visual responses of superior colliculus (SC) neurones in vivo in a variety of ways, in a manner that can be dependent upon visual stimulus properties. How this occurs remains unclear. In this study we aimed to determine how activation of mGluR2 and mGluR3 receptors (Group II) might modulate visual responses, by using field potential and whole-cell patch clamp recording techniques in rat SC slice. Stimulation within the superficial layers of the SC, in the presence of ionotropic glutamate receptor antagonists, evoked IPSCs that were blocked by bicuculline indicating that they are mediated via GABAA receptors. It is likely that these IPSCs were of heterogeneous origin as they showed substantial variation in paired-pulse behaviour. Nevertheless, activation of Group II mGluRs with the group-selective agonist LY354740 (300 nM, bath application) resulted in a reduction of these IPSCs (to 56% of control amplitude), and this was associated with a decrease in paired-pulse depression. At the same concentration, LY354740 did not reduce the EPSC or field-EPSP evoked by stimulation of the retinal input to the SC. The effects of LY354740 on IPSCs were not mimicked by the mGluR3-selective agonist N-acetyl-aspartyl-glutamate (NAAG, 200-500 microM). Stimulation of IPSCs with trains of impulses (10 at 20 Hz) in order to mimic natural activation patterns resulted in sequences of IPSCs that were reduced in amplitude towards the end of the stimulus train. Application of the Group II antagonist LY341495 (100 nM) under these conditions resulted in an increase in later IPSCs in a third of neurones tested. These findings indicate that mGluR2 (but not mGluR3) can selectively modulate GABAergic inhibition in SC, probably via a presynaptic mechanism. Furthermore, these receptors may be activated by synaptically released transmitter during patterns of activation similar to those seen during visual processing. Thus mGluR2 receptors could have a function in activity-dependent modulation of inhibitory processing during visual responses.
Neale
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Department of Visual Science, Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.
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D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D004151:Dipeptides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018756:GABA Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects; D009433:Neural Inhibition / Q000187:drug effects; D018408:Patch-Clamp Techniques; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects / Q000378:metabolism*; D017661:Receptors, Presynaptic / Q000187:drug effects / Q000378:metabolism*; D013477:Superior Colliculi / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects; D013997:Time Factors; D014795:Visual Pathways / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D001643:Bridged Bicyclo Compounds; D004151:Dipeptides; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D011963:Receptors, GABA-A; D018094:Receptors, Metabotropic Glutamate; D017661:Receptors, Presynaptic; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; C027172:isospaglumic acid; D005680:gamma-Aminobutyric Acid; C104753:eglumetad; D001640:Bicuculline