Journal
JOURNAL OF NEUROSCIENCE
Volume 24, Issue 28, Pages 6352-6361Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.0995-04.2004
Keywords
CA1; hippocampus; phosphorylation; protein kinase; translation initiation; synaptic plasticity
Categories
Funding
- NINDS NIH HHS [NS34007, R37 NS034007, R01 NS034007, R29 NS034007] Funding Source: Medline
Ask authors/readers for more resources
Hippocampal long-term depression (LTD) is a long-lasting decrease in synaptic strength that is most commonly studied at glutamatergic inputs to pyramidal cells in hippocampal area CA1. Activation of G-protein-coupled group I ( including types 1 and 5) metabotropic glutamate receptors ( mGluRs) by the pharmacological agonist (RS)-3,5-dihydroxyphenylglycine ( DHPG) elicits LTD in area CA1 of the hippocampus. Recent reports have shown that de novo protein synthesis is necessary for DHPG-induced LTD. However, relatively little is known about the signaling pathways that couple mGluRs to translation initiation. In this study, we investigated whether the activation of the phosphoinositide 3-kinase (PI3K) -Akt-mammalian target of rapamycin ( mTOR) pathway, which has been shown to regulate translation initiation, is necessary for mGluR-LTD induced by DHPG. We found that brief incubations of mouse hippocampal slices with DHPG resulted in increased phosphorylation of Akt and mTOR in hippocampal area CA1. Two structurally unrelated PI3K inhibitors, LY294002 and wortmannin, blocked the DHPG-induced increases in phosphorylation of Akt and mTOR. Biochemical fractionation studies showed that the DHPG-induced increase in the phosphorylation of Akt and mTOR could be detected in synaptoneurosome preparations, and immunohistochemical analysis revealed that similar increases could be detected in both stratum pyramidale and stratum radiatum in area CA1. Finally, we observed that both PI3K inhibitors and rapamycin, an mTOR inhibitor, prevented mGluR-LTD induced by DHPG. Together, our findings indicate that activation of thePI3K-Akt-mTOR signaling cascade is required for mGluR-LTD and suggest that this pathway may couple group I mGluRs to translation initiation in hippocampal area CA1.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available