Complex interactions between mGluR1 and mGluR5 shape neuronal network activity in the rat hippocampus.
Group I metabotropic glutamate receptors (mGluRs) cause increased neuronal excitability that can lead to epileptogenesis and neurodegeneration. Here we have examined how individual members of this subgroup of mGluRs affect synchronised hippocampal synaptic activity under normal and disinhibited conditions similar to those that occur during certain epileptic states. We demonstrate that activation of both mGluR1 and mGluR5 are important in increasing neuronal synaptic excitability by increasing synchrony between cells and driving correlated network activity in circuits that contain, or are devoid of, GABA(A) receptor-mediated synaptic inputs. The precise patterning of activity that occurs is complex and depends upon: (1) the existing pattern of ongoing network activity prior to mGluR activation; and (2) the relative extent of activation of each mGluR subtype. However, mGluR5 appears to be the principal mGluR subtype that initiates bursting activity irrespective of the inhibitory synaptic tone within the neuronal network.
Lanneau
Christophe
C
Neurology CEDD, GlaxoSmithKline, Third Avenue, Harlow Essex CM19 5AW, UK.
Harries
Mark H
MH
Ray
Alison M
AM
Cobb
Stuart R
SR
Randall
Andrew
A
Davies
Ceri H
CH
D000818:Animals; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
C578937:Grm5 protein, rat; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1