Group I mGlu receptors regulate the expression of the neuronal calcium sensor protein VILIP-1 in vitro and in vivo: implications for mGlu receptor-dependent hippocampal plasticity?

Metabotropic glutamate (mGlu) receptors are involved in several forms of synaptic plasticity in the rat hippocampus. Agonists which activate group I mGlu receptors induce slow-onset potentiation without prior tetanization in the hippocampal area CA1. Activation of group I mGlu receptors induces protein synthesis which may contribute to mGlu receptor-dependent forms of long-term plasticity. Calcium-binding proteins are widely considered to comprise key elements for synaptic plasticity. Therefore, we investigated whether the calcium sensor protein VILIP-1 is associated with group I mGlu receptor-mediated plasticity in the dentate gyrus (DG) in vivo.Application of either the group I and II mGlu agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylate (ACPD) or the selective group I agonist (R,S)-3,5-dihydroxyphenylglycine (DHPG) resulted in slow-onset potentiation in the DG of adult rats. In hippocampal cell cultures both agonists elicited an enhanced expression of VILIP-1. In situ hybridization revealed strong hippocampal expression of VILIP-1 and intracerebral application of DHPG to adult rats significantly enhanced hippocampal VILIP-1 expression. The DHPG effects in both, hippocampal cultures and in vivo, were prevented by the group I mGlu receptor antagonist 4-Carboxyphenylglycine (4CPG). Calcium sensor proteins thus appear to be regulated by mGlu receptors in an activity-dependent manner. A specific role for group I mGlu receptors is evident. Furthermore, the sensor proteins may function as molecular switches for the long-term regulation of synaptic plasticity.