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• W2890630644 endingPage "2601" @default.
• W2890630644 startingPage "2590" @default.
• W2890630644 abstract "Abstract In several brain regions, ongoing metabotropic glutamate receptor 1 (mGlu1) transmission has been shown to tonically suppress synaptic levels of Ca 2+ ‐permeable AMPA receptors ( CP ‐ AMPAR s) while pharmacological activation of mGlu1 removes CP ‐ AMPAR s from these synapses. Consistent with this, we previously showed in nucleus accumbens ( NA c) medium spiny neurons ( MSN s) that reduced mGlu1 tone enables and mGlu1 positive allosteric modulation reverses the elevation of CP ‐ AMPAR levels in the NA c that underlies enhanced cocaine craving in the “incubation of craving” rat model of addiction. To better understand mGlu1/ CP ‐ AMPAR interactions, we used a NA c/prefrontal cortex co‐culture system in which NA c MSN s express high CP ‐ AMPAR levels, providing an in vitro model for NA c MSN s after the incubation of cocaine craving. The non‐specific group I orthosteric agonist dihydroxyphenylglycine (10 min) decreased cell surface GluA1 but not GluA2, indicating CP ‐ AMPAR internalization. This was prevented by mGlu1 ( LY 367385) or mGlu5 ( MTEP ) blockade. However, a selective role for mGlu1 emerged in studies of long‐term antagonist treatment. Thus, LY 367385 (24 hr) increased surface GluA1 without affecting GluA2, whereas MTEP (24 hr) had no effect. In hippocampal neurons, scaling up of CP ‐ AMPAR s can occur through a mechanism requiring retinoic acid ( RA ) signaling and new GluA1 synthesis. Consistent with this, the LY 367385‐induced increase in surface GluA1 was blocked by anisomycin (translation inhibitor) or 4‐(diethylamino)‐benzaldehyde ( RA synthesis inhibitor). Thus, mGlu1 transmission tonically suppresses cell surface CP ‐ AMPAR levels, and decreasing mGlu1 tone increases surface CP ‐ AMPAR s via RA signaling and protein translation. These results identify a novel mechanism for homeostatic plasticity in NAc MSNs." @default.
• W2890630644 created "2018-09-27" @default.
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• W2890630644 date "2018-10-14" @default.
• W2890630644 modified "2023-10-14" @default.
• W2890630644 title "mGlu1 tonically regulates levels of calcium‐permeable<scp>AMPA</scp>receptors in cultured nucleus accumbens neurons through retinoic acid signaling and protein translation" @default.
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• W2890630644 doi "https://doi.org/10.1111/ejn.14151" @default.
• W2890630644 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7556732" @default.
• W2890630644 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30222904" @default.
• W2890630644 hasPublicationYear "2018" @default.
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