DHPG-induced LTD in area CA1 of juvenile rat hippocampus; characterisation and sensitivity to novel mGlu receptor antagonists.
We have used extracellular microelectrode recording to characterise a form of long-term depression (LTD) of synaptic transmission that can be induced by metabotropic glutamate (mGlu) receptor activation in the CA1 region of the young (12-18 day old) rat hippocampus. Activation of group I mGlu receptors by the specific agonist 3,5-dihydroxyphenylglyine (DHPG) induced LTD of field excitatory postsynaptic potentials (fEPSPs). The mGlu5 selective agonist 2-chloro-5-hydroxyphenylglycine was also capable of inducing LTD. In contrast, the group II specific agonist DCG-IV had no effect on synaptic transmission, whilst the group III receptor agonist (S)-2-amino-4-phosphonobutyrate elicited a depression that reversed fully upon agonist washout. DHPG-induced LTD could still be generated after prior saturation of electrically-induced NMDA receptor-dependent LTD. DHPG-induced LTD was reversed by tetanic stimulation comprising 100 shocks delivered at 100 Hz. A novel mGlu receptor antagonist, (RS)-2-amino-2-(3-cis and trans-carboxycyclobutyl-3-(9-thioxanthyl)propionic acid) (LY393053) that potently inhibits mGlu1 and mGlu5 receptors, prevented the induction of DHPG-induced LTD. Like other mGlu receptor antagonists, LY393053 also reversed pre-established DHPG-induced LTD. In contrast, a potent mGlu1 selective antagonist (S)-2-methyl-4-carboxyphenylglycine (LY367385) did not prevent the induction of DHPG-induced LTD. In conclusion, DHPG, probably via activation of mGlu5 receptors, is able to induce a robust form of LTD in the CA1 region of the young rat hippocampus that is mechanistically distinct from NMDA receptor-dependent homosynaptic LTD.
Fitzjohn
S M
SM
Department of Anatomy, School of Medical Sciences, MRC Centre for Synaptic Plasticity, University of Bristol, UK. s.m.fitzjohn@bris.ac.uk
Kingston
A E
AE
Lodge
D
D
Collingridge
G L
GL
D000818:Animals; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives* / Q000494:pharmacology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D010648:Phenylacetates / Q000494:pharmacology; D011422:Propionates / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*; D013329:Structure-Activity Relationship
C114785:2-amino-4-phosphono-propinate; C107349:2-chloro-5-hydroxyphenylglycine; D018691:Excitatory Amino Acid Antagonists; D010648:Phenylacetates; D011422:Propionates; D018094:Receptors, Metabotropic Glutamate; D008734:Methoxyhydroxyphenylglycol; D005998:Glycine; C010117:3,4-dihydroxyphenylglycol