title: Trafficking of calcium-permeable and calcium-impermeable AMPA receptors in nucleus accumbens medium spiny neurons co-cultured with prefrontal cortex neurons.
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.
authors.affiliation: Department of Neuroscience, The Chicago Medical School at Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA.
authors.forename: Craig T
authors.initials: CT
authors.lastname: Werner
authors.affiliation: Department of Neuroscience, The Chicago Medical School at Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA.
authors.forename: Conor H
authors.initials: CH
authors.lastname: Murray
authors.affiliation: Department of Neuroscience, The Chicago Medical School at Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA.
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Reimers
authors.affiliation: Department of Neuroscience, The Chicago Medical School at Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA.
authors.forename: Niravkumar M
authors.initials: NM
authors.lastname: Chauhan
authors.affiliation: Department of Neuroscience, The Chicago Medical School at Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA.
authors.forename: Kenneth K Y
authors.initials: KK
authors.lastname: Woo
authors.affiliation: Department of Neuroscience, The Chicago Medical School at Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA.
authors.forename: Hanna M
authors.initials: HM
authors.lastname: Molla
authors.affiliation: Department of Neuroscience, The Chicago Medical School at Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Loweth
authors.affiliation: Department of Neuroscience, The Chicago Medical School at Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA. Electronic address: marina.wolf@rosalindfranklin.edu.
authors.forename: Marina E
authors.initials: ME
authors.lastname: Wolf
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D018920:Coculture Techniques; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D057507:Mice, 129 Strain; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
chemical_list: D018377:Neurotransmitter Agents; D018091:Receptors, AMPA; C527701:enhanced cyan fluorescent protein; D049452:Green Fluorescent Proteins; D017868:Cyclic AMP-Dependent Protein Kinases; D002118:Calcium
keywords: AMPA receptors; Medium spiny neurons; Nucleus accumbens; Trafficking