Interneuron subtype specific activation of mGluR1/5 during epileptiform activity in hippocampus.
OBJECTIVE
Specific inhibitory interneurons in area CA1 of the hippocampus, notably those located in stratum oriens-alveus (O/A-INs), are selectively vulnerable in patients and animal models of temporal lobe epilepsy (TLE). The excitotoxic mechanisms underlying the selective vulnerability of interneurons have not been identified but could involve group I metabotropic glutamate receptor subtypes (mGluR1/5), which have generally proconvulsive actions and activate prominent cationic currents and calcium responses specifically in O/A-INs.


METHODS
In this study, we examine the role of mGluR1/5 in interneurons during epileptiform activity using whole-cell recordings from CA1 O/A-INs and selective antagonists of mGluR1α (LY367385) and mGluR5 (MPEP) in a disinhibited rat hippocampal slice model of epileptiform activity.


RESULTS
Our data indicate more prominent epileptiform burst discharges and paroxysmal depolarizations (PDs) in O/A-INs than in interneurons located at the border of strata radiatum and lacunosum/moleculare (R/LM-INs). In addition, mGluR1 and mGluR5 significantly contributed to epileptiform responses in O/A-INs but not in R/LM-INs. Epileptiform burst discharges in O/A-INs were partly dependent on mGluR5. PDs and associated postsynaptic currents were dependent on both mGluR1α and mGluR5. These receptors contributed differently to postsynaptic currents underlying PDs, with mGluR5 contributing to the fast and slow components and mGluR1α to the slow component.


CONCLUSIONS
These findings support interneuron subtype-specific activation and differential contributions of mGluR1α and mGluR5 to epileptiform activity in O/A-INs, which could be important for their selective vulnerability in TLE.
Sanon
Nathalie T
NT
Groupe de Recherche sur le Système Nerveux Central, Département de Physiologie, Université de Montréal, Quebec, Canada.
Pelletier
Joe Guillaume
JG
Carmant
Lionel
L
Lacaille
Jean-Claude
JC
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000494:pharmacology; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology*; D066298:In Vitro Techniques; D007395:Interneurons / Q000145:classification* / Q000502:physiology*; D008297:Male; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000378:metabolism*
D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; C578937:Grm5 protein, rat; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D001640:Bicuculline