PMID- 37034633
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231019
DP  - 2023 Apr 2
TI  - Dopamine D1 and NMDA receptor co-regulation of protein translation in cultured 
      nucleus accumbens neurons.
LID - 2023.04.02.535293 [pii]
LID - 10.1101/2023.04.02.535293 [doi]
AB  - Protein translation is essential for some forms of synaptic plasticity. We used 
      nucleus accumbens (NAc) medium spiny neurons (MSN), co-cultured with cortical 
      neurons to restore excitatory synapses, to examine whether dopamine modulates 
      protein translation in NAc MSN. FUNCAT was used to measure translation in MSNs 
      under basal conditions and after disinhibiting excitatory transmission using the 
      GABA(A) receptor antagonist bicuculline (2 hr). Under basal conditions, 
      translation was not altered by the D1-class receptor (D1R) agonist SKF81297 or 
      the D2-class receptor (D2R) agonist quinpirole. Bicuculline alone robustly 
      increased translation. This was reversed by quinpirole but not SKF81297. It was 
      also reversed by co-incubation with the D1R antagonist SCH23390, but not the D2R 
      antagonist eticlopride, suggesting dopaminergic tone at D1Rs. This was surprising 
      because no dopamine neurons are present. An alternative explanation is that 
      bicuculline activates translation by increasing glutamate tone at NMDA receptors 
      (NMDAR) within D1R/NMDAR heteromers, which have been described in other cell 
      types. Supporting this, immunocytochemistry and proximity ligation assays 
      revealed D1/NMDAR heteromers on NAc cells both in vitro and in vivo. Further, 
      bicuculline's effect was reversed to the same extent by SCH23390 alone, the NMDAR 
      antagonist APV alone, or SCH23390+APV. These results suggest that: 1) excitatory 
      synaptic transmission stimulates translation in NAc MSNs, 2) this is opposed when 
      glutamate activates D1R/NMDAR heteromers, even in the absence of dopamine, and 3) 
      antagonist occupation of D1Rs within the heteromers prevents their activation. 
      Our study is the first to suggest a role for D2 receptors and D1R/NMDAR 
      heteromers in regulating protein translation.
FAU - Zimbelman, Alexa R
AU  - Zimbelman AR
AD  - Department of Psychology and Neuroscience, North Central College, Naperville, IL 
      60540.
FAU - Wong, Benjamin
AU  - Wong B
AD  - Department of Psychology and Neuroscience, North Central College, Naperville, IL 
      60540.
FAU - Murray, Conor H
AU  - Murray CH
AD  - Department of Neuroscience, The Chicago Medical School at Rosalind Franklin 
      University of Medicine and Science, North Chicago, IL, 60064.
AD  - Present address: Department of Psychiatry and Behavioral Neuroscience, University 
      of Chicago, Chicago, IL.
FAU - Wolf, Marina E
AU  - Wolf ME
AUID- ORCID: 0000-0001-9129-3432
AD  - Department of Neuroscience, The Chicago Medical School at Rosalind Franklin 
      University of Medicine and Science, North Chicago, IL, 60064.
AD  - These authors contributed equally.
AD  - Present address: Department of Behavioral Neuroscience, Oregon Health & Science 
      University, Portland, OR 97212.
FAU - Stefanik, Michael T
AU  - Stefanik MT
AUID- ORCID: 0000-0002-8025-3440
AD  - Department of Psychology and Neuroscience, North Central College, Naperville, IL 
      60540.
AD  - Department of Neuroscience, The Chicago Medical School at Rosalind Franklin 
      University of Medicine and Science, North Chicago, IL, 60064.
AD  - These authors contributed equally.
LA  - eng
PT  - Preprint
DEP - 20230402
PL  - United States
TA  - bioRxiv
JT  - bioRxiv : the preprint server for biology
JID - 101680187
PMC - PMC10081306
OTO - NOTNLM
OT  - Dopamine
OT  - FUNCAT
OT  - NMDA receptor
OT  - Protein translation
OT  - Proximity Ligation Assay
COIS- Conflict of Interest: The authors declare no competing financial interests.
EDAT- 2023/04/11 06:00
MHDA- 2023/04/11 06:01
PMCR- 2023/04/07
CRDT- 2023/04/10 04:11
PHST- 2023/04/11 06:00 [pubmed]
PHST- 2023/04/11 06:01 [medline]
PHST- 2023/04/10 04:11 [entrez]
PHST- 2023/04/07 00:00 [pmc-release]
AID - 2023.04.02.535293 [pii]
AID - 10.1101/2023.04.02.535293 [doi]
PST - epublish
SO  - bioRxiv [Preprint]. 2023 Apr 2:2023.04.02.535293. doi: 10.1101/2023.04.02.535293.