Wang W, Zhang Z, Shang J, Jiang ZZ, Wang S, Liu Y et al. Activation of group I metabotropic glutamate receptors induces long-term depression in the hippocampal CA1 region of adult rats in vitro. Neurosci Res 62: 43-50

National Drug Screening Laboratory, New Drug Screening Center, China Pharmaceutical University, Nanjing, China.
Neuroscience Research (Impact Factor: 1.94). 07/2008; 62(1):43-50. DOI: 10.1016/j.neures.2008.06.002
Source: PubMed


Previous studies have implicated that long-term depression (LTD) was developmentally regulated since LTD can be readily induced by low frequency stimulation (LFS) in acute hippocampal slices prepared from juvenile but not adult animals. Here, we have examined the LTD induced by LFS (1Hz, 900 pulses) paired with a certain pattern at the Schaffer collateral-CAl synapse in adult hippocampal slices. We found that, in the 90-day-old rat hippocampus, LTD could be induced reliably by LFS paired with stronger stimulus intensity than that used during baseline recording. However, this synaptic depression could be completely abolished by application of metabotropic glutamate receptor (mGluR) antagonist (S)-amethyl-4-carboxyphenylglycine (MCPG) which had no effect on that induced by the same protocol in the 16-day-old rat hippocampus. Furthermore, preincubation with group I mGluR antagonist, 2-methyl-6-(phenylethynyl)-pyridine (MPEP) and (S)-2-methyl-4-carboxyphenylglycine (LY367385), also completely prevented the LFS-induced LTD. In contrast, group II mGluR antagonist (2S)-a-ethylglutamic acid (EGLU), N-methyl-d-aspartate (NMDA) receptor antagonist APV and voltage-gated calcium channel antagonist nimodipine had no effect on the LFS-induced LTD. Taken together, these observations suggest that LFS paired with strong stimulus strength can efficiently induce group I mGluR-dependent LTD in the adult hippocampal CA1 region, proving insight into the functional significance of hippocampal mGluR-mediated LTD in learning and memory.

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    • "Hippocampal LTD, mGluR5, and ECs Y Izumi and CF Zorumski Furthermore, it has been recently reported that LFS-LTD can be induced after DHPG-LTD (Wang et al, 2008). CHPG, a more specific mGluR5 agonist (Doherty et al, 1997), has been used less often for LTD studies, but has been found to induce or augment LTD in several studies (Palmer et al, 1997; Lanté et al, 2006; Neyman and Manahan-Vaughan, 2008). "
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    ABSTRACT: In the CA1 region of the rat hippocampus, metabotropic glutamate receptor-5 (mGluR5) and cannabinoid-1 receptors (CB1Rs) are believed to participate in long-term synaptic depression (LTD). How mGluRs and CB1Rs interact to promote LTD remains uncertain. In this study, we examined LTD induced by CB1R agonists, mGluR5 agonists, and low-frequency electrical stimulation (LFS) of the Schaffer collateral pathway. Synthetic CB1R agonists induced robust LTD that was mimicked by the endocannabinoid (EC), noladin ether (NLDE), but not by anandamide. 2-Arachidonylglycerol (2AG) produced only a small degree of LTD. The selective mGluR5 agonist, namely (RS)-2-chloro-5-hydroxyphenylglycine (CHPG), also induced robust LTD, and CHPG and NLDE occluded each other's effects. Similarly, CHPG and NLDE occluded LFS-induced LTD, and LTD resulting from all three treatments was blocked by a CB1R antagonist. CHPG-LTD and NLDE-LTD were insensitive to N-methyl-D-aspartate receptor (NMDAR) block, even though LFS-LTD requires NMDARs. LTD induced by LFS or CHPG, but not NLDE-LTD, was blocked by a selective mGluR5 antagonist. (RS)-3,5-dihydroxyphenylglycine (DHPG), a less selective group I mGluR agonist, also induced LTD, but its effects were not blocked by mGluR5 or CB1R antagonists. Furthermore, DHPG-LTD was additive with LFS-LTD and CHGP-LTD. These results suggest that NMDARs, mGluR5, and CB1Rs participate in a cascade that underlies LFS-LTD and that release of an EC and CB1R activation occur downstream of NMDARs and mGluR5. Furthermore, DHPG induces a form of LTD that differs mechanistically from LFS-induced depression.
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    • "LTD was effectively induced by prolonged low-frequency stimulation (LFS) of 1-5 Hz (Doyere et al., 1996; Dudek and Bear, 1992) in CA1 or by repeated low-frequency paired-pulse stimulation in CA1 and DG (Thiels et al., 1996). Metabotropic glutamate receptors (mGluRs), in addition to N-methyl-D-aspartate receptors (NMDARs), have been suggested to play a role in LTD in hippocampal CA1 (Kleppisch et al., 2001; Manahan-Vaughan, 1997; Neyman and Manahan- Vaughan, 2008; Wang et al., 2008). To our knowledge, there has been no study on LTD of the direct EC to CA3 pathway. "
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