Group I mGluRs modulate the pattern of non-synaptic epileptiform activity in the hippocampus.
The hippocampus is well known for its susceptibility to epileptic seizures, in part because of its neuronal architecture that facilitates synchronization. Although synaptic networks are important for the genesis and spread of epileptiform activity, synchronization of neuronal activity can occur when action potential-dependent chemical synaptic transmission is absent. In particular, it is possible to induce epileptiform activity by perfusing hippocampal slices with a low-Ca(2+)/high-K(+) mediums. Using extracellular recording in area CA1 we have characterized the effects of metabotropic glutamate receptor (mGluR) activation on this non-synaptic bursting activity. Under control conditions, bursting occurred at intervals of 14-86 s with each burst comprising a long (up to 44 s) negative-going field potential of 2 to 13 mV superimposed upon which was sustained firing of population spikes. Activation of group I mGluRs by (S)-3,5-dihydroxyphenylglycine (DHPG) (25 microM) caused a dramatic increase in burst frequency (up to five-fold), which was accompanied by a decrease in the duration and amplitude of bursts. The selective mGluR(1) antagonist 2-methyl-4-carboxyphenylglycine (LY367385) and the selective mGluR(5) antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP) both restricted the increase in burst frequency induced by DHPG. However, only LY367385 inhibited the decrease in burst duration and amplitude. Combined application of both antagonists prevented all DHPG-induced changes in bursting activity. These data provide evidence for a role of both mGluR(1) and mGluR(5) subtypes in changing the frequency of non-synaptic bursting, with mGluR(1) alone causing alterations in burst duration and amplitude. These effects are likely to contribute to the group I mGluR-induced changes in synaptic epileptic activity that are already well documented.
Thuault
Sébastien J
SJ
MRC Centre for Synaptic Plasticity, Department of Anatomy, School of Medical Sciences, University of Bristol, University Walk, Bristol BS8 1TD, UK. seb.thuaulet@bristol.ac.uk
Davies
Ceri H
CH
Randall
Andy D
AD
Collingridge
Graham L
GL
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D004827:Epilepsy / Q000503:physiopathology; D005260:Female; D066298:In Vitro Techniques; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology
D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1