Group II metabotropic glutamate (mGlu) receptors are known to induce a long-term depression (LTD) of synaptic transmission in many brain regions including the amygdala. However the roles of the individual receptor subtypes, mGlu2 and mGlu3, in LTD are not well understood. In particular, it is unclear whether activation of mGlu3 receptors is sufficient to induce LTD at synapses in the CNS. In the present study, advantage was taken of a Wistar rat strain not expressing mGlu2 receptors (Ceolin et al., 2011) to investigate the function of mGlu3 receptors in the amygdala. In this preparation, the group II agonist, DCG-IV induced an LTD of the cortical, but not the intra-nuclear, synaptic input to the lateral amygdala. This LTD was concentration dependent and was blocked by the group II mGlu receptor antagonist, LY341495. To investigate further the role of mGlu3 receptors, we used LY395756 (an mGlu2 agonist and mGlu3 antagonist), which acts as a pure mGlu3 receptor antagonist in this rat strain. This compound alone had no effect on basal synaptic transmission, but blocked the LTD induced by DCG-IV. Furthermore, we found that DCG-IV also induces LTD in mGlu2 receptor knock-out (KO) mice to a similar extent as in wild-type mice. This confirms that the activation of mGlu3 receptors alone is sufficient to induce LTD at this amygdala synapse. To address whether mGlu2 activation alone is also sufficient to induce LTD at this synapse we used LY541850 (the active enantiomer of LY395756) in wild-type mice. LY541850 induced a substantial LTD showing that either receptor alone is capable of inducing LTD in this pathway. This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'.
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