Gα_q-deficient mice lack metabotropic glutamate receptor-dependent long-term depression but show normal long-term potentiation in the hippocampal CA1 region

Long-term potentiation (LTP) and depression (LTD) are potential cellular mechanisms involved in learning and memory. Group I metabotropic glutamate receptors (mGluR), which are linked to heterotrimeric G-proteins of the G_q family (G_q and G₁₁), have been reported to facilitate both hippocampal LTP and LTD. To evaluate their functional role in synaptic plasticity, we studied LTD and LTP in the CA1 region of the hippocampus from wild-type, Gα_q(-/-), and Gα₁₁(-/-) mice. Basic parameters of the synaptic transmission were not altered in Gα_q(-/-) and Gα₁₁(-/-) mice. Moreover, these mice showed normal LTP in response to a strong tetanus and to a weak tetanus. However, LTD induced either by a group I mGluRs agonist or by paired-pulse low-frequency stimulation (PP-LFS) was absent in Gα_q(-/-) mice. Moreover, PP-LFS caused potentiation of the synaptic transmission in these mice that was not affected by the NMDAR antagonist AP-5. These results show that G_q plays a crucial role in the mGluR-dependent LTD, whereas hippocampal LTP is not affected by the lack of a single member of the G_q family.