Trafficking of calcium-permeable and calcium-impermeable AMPA receptors in nucleus accumbens medium spiny neurons co-cultured with prefrontal cortex neurons

Craig T. Werner, Conor H. Murray, Jeremy M. Reimers, Niravkumar M. Chauhan, Kenneth K.Y. Woo, Hanna M. Molla, Jessica A. Loweth, Marina Wolf

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

AMPA receptor (AMPAR) transmission onto medium spiny neurons (MSNs) of the adult rat nucleus accumbens (NAc) is normally dominated by GluA2-containing, Ca2+-impermeable AMPAR (CI-AMPARs). However, GluA2-lacking, Ca2+-permeable AMPA receptors (CP-AMPARs) accumulate after prolonged withdrawal from extended-access cocaine self-administration and thereafter their activation is required for the intensified (incubated) cue-induced cocaine craving that characterizes prolonged withdrawal from such regimens. These findings suggest the existence of mechanisms in NAc MSNs that differentially regulate CI-AMPARs and CP-AMPARs. Here, we compared trafficking of GluA1A2 CI-AMPARs and homomeric GluA1 CP-AMPARs using immunocytochemical assays in cultured NAc MSNs plated with prefrontal cortical neurons to restore excitatory inputs. We began by evaluating constitutive internalization of surface receptors and found that this occurs more rapidly for CP-AMPARs. Next, we studied receptor insertion into the membrane; combined with past results, the present findings suggest that activation of protein kinase A accelerates insertion of both CP-AMPARs and CI-AMPARs. We also studied constitutive cycling (net loss of receptors from the membrane under conditions where internalization and recycling are both occurring). Interestingly, although CP-AMPARs exhibit faster constitutive internalization, they cycle at similar rates as CI-AMPARs, suggesting faster reinsertion of CP-AMPARs. In studies of synaptic scaling, long-term (24 h) activity blockade increased surface expression and cycling rates of CI-AMPARs but not CP-AMPARs, whereas long-term increases in activity produced more pronounced scaling down of CI-AMPARs than CP-AMPARs but did not alter receptor cycling. These findings can be used to evaluate and generate hypotheses regarding AMPAR plasticity in the rat NAc following cocaine exposure.

Original languageEnglish (US)
Pages (from-to)224-232
Number of pages9
JournalNeuropharmacology
Volume116
DOIs
StatePublished - Apr 1 2017
Externally publishedYes

Fingerprint

AMPA Receptors
Nucleus Accumbens
Prefrontal Cortex
Calcium
Neurons
Cocaine
Self Administration
Membranes
Recycling
Cyclic AMP-Dependent Protein Kinases
Cues

Keywords

  • AMPA receptors
  • Medium spiny neurons
  • Nucleus accumbens
  • Trafficking

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

Cite this

Trafficking of calcium-permeable and calcium-impermeable AMPA receptors in nucleus accumbens medium spiny neurons co-cultured with prefrontal cortex neurons. / Werner, Craig T.; Murray, Conor H.; Reimers, Jeremy M.; Chauhan, Niravkumar M.; Woo, Kenneth K.Y.; Molla, Hanna M.; Loweth, Jessica A.; Wolf, Marina.

In: Neuropharmacology, Vol. 116, 01.04.2017, p. 224-232.

Research output: Contribution to journalArticle

Werner, Craig T. ; Murray, Conor H. ; Reimers, Jeremy M. ; Chauhan, Niravkumar M. ; Woo, Kenneth K.Y. ; Molla, Hanna M. ; Loweth, Jessica A. ; Wolf, Marina. / Trafficking of calcium-permeable and calcium-impermeable AMPA receptors in nucleus accumbens medium spiny neurons co-cultured with prefrontal cortex neurons. In: Neuropharmacology. 2017 ; Vol. 116. pp. 224-232.
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