ro-67-4853 and 3-5-dihydroxyphenylglycine

Neural circuits formed during postnatal development have to be maintained stably thereafter, but their mechanisms remain largely unknown. Here we report that the metabotropic glutamate receptor subtype 1 (mGluR1) is essential for the maintenance of mature synaptic connectivity in the dorsal lateral geniculate nucleus (dLGN). In mGluR1 knockout (mGluR1-KO) mice, strengthening and elimination at retinogeniculate synapses occurred normally until around postnatal day 20 (P20). However, during the subsequent visual-experience-dependent maintenance phase, weak retinogeniculate synapses were newly recruited. These changes were similar to those of wild-type (WT) mice that underwent visual deprivation or inactivation of mGluR1 in the dLGN from P21. Importantly, visual deprivation was ineffective in mGluR1-KO mice, and the changes induced by visual deprivation in WT mice were rescued by pharmacological activation of mGluR1 in the dLGN. These results demonstrate that mGluR1 is crucial for the visual-experience-dependent maintenance of mature synaptic connectivity in the dLGN.

Topics: Animals; Carbamates; Geniculate Bodies; Glycine; Mice; Mice, Knockout; Receptors, Metabotropic Glutamate; Resorcinols; Retina; Sensory Deprivation; Synapses; Thalamus; Visual Pathways; Xanthenes

As postsynaptic metabotropic subtype 1 (mGlu1) receptors are present in the thalamus, we have investigated the effect of potentiating and antagonising mGlu1 receptors on responses of thalamic neurones to noxious sensory stimulation. Extracellular recordings were made in vivo with multi-barrel iontophoretic electrodes from single neurones in the thalamus of urethane-anaesthetised rats. Responses to iontophoretic applications of the Group I mGlu agonist 3,5-dihydroxy-phenylglycine (DHPG) were selectively potentiated by co-application of the mGlu1 positive allosteric modulator Ro67-4853, whereas they were selectively reduced upon co-application of the mGlu1 receptor orthosteric antagonist LY367385. This indicates that thalamic DHPG responses are mediated primarily via mGlu1 receptors, consistent with the high postsynaptic levels of this receptor in the thalamus. Furthermore, potentiation of DHPG responses by Ro67-4853 were greater when the initial DHPG response was of a low magnitude. Ro67-4853 also potentiated responses of thalamic neurones to noxious thermal stimulation, whilst having little effect on the baseline activity of nociceptive neurones. By contrast, nociceptive responses were reduced by LY367385. In a further series of experiments we found that inactivation of somatosensory cortex by cooling resulted in a reduction of thalamic nociceptive responses. These results underline the importance of mGlu1 receptors in the processing of sensory information in the thalamus, particularly with respect to nociceptive responses. Furthermore, the involvement of mGlu1 receptors may reflect the activity of descending cortico-thalamic afferents.

Topics: Action Potentials; Animals; Benzoates; Carbamates; Cold Temperature; Excitatory Amino Acid Agents; Excitatory Amino Acid Agonists; Excitatory Amino Acid Antagonists; Glycine; Hot Temperature; Male; Neural Pathways; Neurons; Nociception; Rats; Rats, Wistar; Receptors, Metabotropic Glutamate; Resorcinols; Somatosensory Cortex; Thalamus; Xanthenes