mGluRs regulate FMRP and Fmr1 mRNA localization in dendrites. A, B, E, DHPG stimulation (5 min) resulted in increased FMRP levels in dendrites. C, KCl stimulation (10 min) also increased FMRP levels (p < 0.05) in dendrites. This response was entirely inhibited by an mGluR antagonist, MCPG, but not by the AMPAR antagonist, CNQX. D, Bath application of mGluR5 antagonist MPEP blocked (p < 0.05) the KCl-regulated increase of FMRP in dendrites whereas mGluR1 antagonist LY-367385 did not. Bars indicate percentage difference of control compared with KCl application (KCl), MPEP compared with MPEP plus KCl (MPEP), and LY compared with LY plus KCl (LY). E, Treatment of neurons with the group I mGluR agonist DHPG resulted in increased dendritic FMRP levels (p < 0.05), a response not observed with AMPA. F, Blockade of the mGluR pathway through either PKC inactivation (RO-32) or chelating internal calcium (BAPTA-AM) abolished the dendritic localization of FMRP in response to mGluR activation. G, Fmr1 mRNA also demonstrated mGluR-dependent dendritic trafficking. DHPG activation of mGluR receptors localized the mRNA in dendrites (p < 0.05). H, Blockade of the mGluR pathway, as in F, also prevented Fmr1 mRNA localization. Histograms depict mean FMRP or Fmr1 mRNA IF intensity in response to various stimuli or the percentage difference in immunofluorescence intensity of an antagonist before and after stimulus. Unstimulated cultures in each histogram are labeled “C.” All culture conditions contain antagonists APV and CNQX, except where testing AMPA or NMDA. Scale bar, 10 μm.