title: Distinct mechanisms contribute to agonist and synaptically induced metabotropic glutamate receptor long-term depression.
abstract: Metabotropic glutamate receptor mediated long-term depression (mGlu receptor LTD) is evoked in hippocampal area CA1 chemically by the agonist 3,5-Dihydroxyphenylglycine (DHPG, agonist LTD) and synaptically by paired-pulse low frequency stimulation (PP-LFS, synaptic LTD). We tested the hypothesis that different expression mechanisms regulate mGlu receptor LTD in 15-21 day old rats through neurophysiologic recordings in CA1. Several findings, in fact, suggest that agonist and synaptic mGlu receptor LTD are expressed through different mechanisms. First, neither LTD occluded the other. Second, a low calcium solution enhanced agonist LTD but did not alter synaptic LTD. Third, application of the mGlu receptor antagonist LY341495 (2S-2-amino-2-(1S,2S-2-carboxycyclopropyl-1-yl)-3-(xanth-9-yl)propanoic acid) reversed agonist LTD expression, but did not alter synaptic LTD. Finally, an N-type, voltage-dependent calcium channel antagonist, ω-conotoxin GVIA (CTX), reduced agonist LTD expression by 35%, but did not alter synaptic LTD. CTX also blocked the increase in the paired-pulse ratio associated with agonist LTD. This study cautions against assuming that agonist and synaptic LTD are equivalent as several components underlying their expression appear to differ. Moreover, the data suggest that agonist LTD, but not synaptic LTD, has a presynaptic, N-channel mediated component.
authors.affiliation: University of Pennsylvania, Department of Neuroscience, United States.
authors.forename: Timothy
authors.initials: T
authors.lastname: Connelly
authors.forename: Yuan
authors.initials: Y
authors.lastname: Fan
authors.forename: Paul E
authors.initials: PE
authors.lastname: Schulz
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D066298:In Vitro Techniques; D014176:Protein Biosynthesis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists* / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D013997:Time Factors
chemical_list: D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D018094:Receptors, Metabotropic Glutamate