Group III metabotropic glutamate receptors control corticothalamic synaptic transmission in the rat thalamus in vitro

1 Corticothalamic (CT) EPSPs evoked at ≤ 0.1 Hz were recorded from thalamocortical neurones in the rat dorsal lateral geniculate nucleus in vitro , with both GABA A and GABA B receptors blocked. 2 The group III metabotropic glutamate (mGlu) receptor agonists L‐2‐amino‐4‐phosphono‐butyric acid (L‐AP4) and O ‐phospho‐L‐serine (L‐SOP) both caused a concentration‐dependent depression of the CT EPSP. The maximum depression and EC 50 values for these effects were 64.4 ± 3.8 % and 88.0 ± 24.7 μ m for L‐AP4, and 42.0 ± 2.5 % and 958 ± 492 μ m for L‐SOP, respectively (means ± s.e.m. ). Neither agonist had any effect on membrane potential or input resistance. 3 The depression of the CT EPSP caused by L‐AP4 was reversed using the group III antagonist ( S )‐2‐amino‐2‐methyl‐4‐phosphonobutanoic acid (MAP4, 1 mM), and the group II/III antagonist LY341495 (3 μ m ), but not using the group II antagonist (2 S )‐α‐ethylglutamic acid (300 μ m ). The potencies of L‐AP4, L‐SOP and LY341495 indicate that this action of L‐AP4 is mediated via mGlu7 and mGlu8 and not mGlu4 receptors. 4 Neither MAP4 nor LY341495 had any effect on the CT EPSPs evoked by 10 Hz trains of five stimuli, indicating the lack of endogenous activation of group III mGlu receptors in the thalamus during short bursts of cortical input. However, the magnitude of the depression caused by L‐AP4 indicates that any physiological activation of group III mGlu receptors would have a profound effect on the CT input to the thalamus, and hence cortical control of thalamic function.