Ionotropic and metabotropic glutamate receptors regulate protein translation in co-cultured nucleus accumbens and prefrontal cortex neurons

Michael T. Stefanik, Courtney Sakas, Dennis Lee, Marina Wolf

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The regulation of protein translation by glutamate receptors and its role in plasticity have been extensively studied in the hippocampus. In contrast, very little is known about glutamatergic regulation of translation in nucleus accumbens (NAc) medium spiny neurons (MSN), despite their critical role in addiction-related plasticity and recent evidence that protein translation contributes to this plasticity. We used a co-culture system, containing NAc MSNs and prefrontal cortex (PFC) neurons, and fluorescent non-canonical amino acid tagging (FUNCAT) to visualize newly synthesized proteins in neuronal processes of NAc MSNs and PFC pyramidal neurons. First, we verified that the FUNCAT signal reflects new protein translation. Next, we examined the regulation of translation by group I metabotropic glutamate receptors (mGluRs) and ionotropic glutamate receptors by incubating co-cultures with agonists or antagonists during the 2-h period of non-canonical amino acid labeling. In NAc MSNs, basal translation was modestly reduced by blocking Ca2+-permeable AMPARs whereas blocking all AMPARs or suppressing constitutive mGluR5 signaling enhanced translation. Activating group I mGluRs with dihydroxyphenylglycine increased translation in an mGluR1-dependent manner in NAc MSNs and PFC pyramidal neurons. Disinhibiting excitatory transmission with bicuculline also increased translation. In MSNs, this was reversed by antagonists of mGluR1, mGluR5, AMPARs or NMDARs. In PFC neurons, AMPAR or NMDAR antagonists blocked bicuculline-stimulated translation. Our study, the first to examine glutamatergic regulation of translation in MSNs, demonstrates regulatory mechanisms specific to MSNs that depend on the level of neuronal activation. This sets the stage for understanding how translation may be altered in addiction.

Original languageEnglish (US)
Pages (from-to)62-75
Number of pages14
JournalNeuropharmacology
Volume140
DOIs
StatePublished - Sep 15 2018
Externally publishedYes

Fingerprint

Ionotropic Glutamate Receptors
Metabotropic Glutamate Receptors
Nucleus Accumbens
Protein Biosynthesis
Prefrontal Cortex
Neurons
Bicuculline
Pyramidal Cells
Coculture Techniques
Amino Acids
Glutamate Receptors
Hippocampus
Proteins

Keywords

  • FUNCAT
  • Glutamate receptors
  • Medium spiny neuron
  • Nucleus accumbens
  • Prefrontal cortex
  • Protein translation

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

Cite this

Ionotropic and metabotropic glutamate receptors regulate protein translation in co-cultured nucleus accumbens and prefrontal cortex neurons. / Stefanik, Michael T.; Sakas, Courtney; Lee, Dennis; Wolf, Marina.

In: Neuropharmacology, Vol. 140, 15.09.2018, p. 62-75.

Research output: Contribution to journalArticle

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