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Group III mGluR regulation of synaptic transmission at the SC-CA1 synapse is developmentally regulated.

Ayala JE, Niswender CM, Luo Q, Banko JL, Conn PJ
Neuropharmacology. 2008 54 (5): 804-14

PMID: 18255102 · PMCID: PMC2431171 · DOI:10.1016/j.neuropharm.2007.12.009

Group III metabotropic glutamate receptors (mGluRs) reduce synaptic transmission at the Schaffer collateral-CA1 (SC-CA1) synapse in rats by a presynaptic mechanism. Previous studies show that low concentrations of the group III-selective agonist, L-AP4, reduce synaptic transmission in slices from neonatal but not adult rats, whereas high micromolar concentrations reduce transmission in both age groups. L-AP4 activates mGluRs 4 and 8 at much lower concentrations than those required to activate mGluR7, suggesting that the group III mGluR subtype modulating transmission is a high affinity receptor in neonates and a low affinity receptor in adults. The previous lack of subtype selective ligands has made it difficult to test this hypothesis. We have measured fEPSPs in the presence of novel subtype selective agents to address this question. We show that the effects of L-AP4 can be blocked by LY341495 in both neonates and adults, verifying that these effects are mediated by mGluRs. In addition, the selective mGluR8 agonist, DCPG, has a significant effect in slices from neonatal rats but does not reduce synaptic transmission in adult slices. The mGluR4 selective allosteric potentiator, PHCCC, is unable to potentiate the L-AP4-induced effects at either age. Taken together, our data suggest that group III mGluRs regulate transmission at the SC-CA1 synapse throughout development but there is a developmental regulation of the subtypes involved so that both mGluR7 and mGluR8 serve this role in neonates whereas mGluR7 is involved in regulating transmission at this synapse throughout postnatal development.

MeSH Terms (23)

Age Factors Amino Acids Aminobutyrates Animals Animals, Newborn Cell Line, Transformed Dose-Response Relationship, Drug Excitatory Amino Acid Agonists Excitatory Amino Acid Antagonists Hippocampus Humans In Vitro Techniques Male Neural Pathways Neurons Patch-Clamp Techniques Rats Rats, Sprague-Dawley Receptors, AMPA Synapses Synaptic Transmission Transfection Xanthenes

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