PMID- 35098156
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221016
IS  - 2665-945X (Electronic)
IS  - 2665-945X (Linking)
VI  - 2
DP  - 2021
TI  - M1 receptors interacting with NMDAR enhance delay-related neuronal firing and 
      improve working memory performance.
LID - 100016 [pii]
LID - 10.1016/j.crneur.2021.100016 [doi]
AB  - The recurrent excitatory circuits in dlPFC underlying working memory are known to 
      require activation of glutamatergic NMDA receptors (NMDAR). The neurons in these 
      circuits also rely on acetylcholine to maintain persistent activity, with 
      evidence for actions at both nicotinic alpha7 receptors and muscarinic M1 receptors 
      (M1R). It is known that nicotinic alpha7 receptors interact with NMDAR in these 
      circuits, but the interactions between M1R and NMDAR on dlPFC neuronal activity 
      are unknown. Here, we investigated whether M1Rs contribute to the permissive 
      effects of ACh in dlPFC circuitry underlying working memory via interactions with 
      NMDA receptors. We tested interactions between M1Rs and NMDARs in vivo on single 
      neuron activity in rhesus macaques performing a working memory task, as well as 
      on working memory behavior in rodents following infusion of M1R and NMDAR 
      compounds into mPFC. We report that M1R antagonists block the enhancing effects 
      of NMDA application, consistent with M1R permissive actions. Conversely, M1R 
      positive allosteric modulators prevented the detrimental effects of NMDAR 
      blockade in single neurons in dlPFC and on working memory performance in rodents. 
      These data support an interaction between M1R and NMDARs in working memory 
      circuitry in both primates and rats, and suggest M1Rs contribute to the 
      permissive actions of ACh in primate dlPFC. These results are consistent with 
      recent data suggesting that M1R agonists may be helpful in the treatment of 
      schizophrenia, a cognitive disorder associated with NMDAR dysfunction.
FAU - Galvin, Veronica C
AU  - Galvin VC
AD  - Department of Neuroscience, Yale University School of Medicine, New Haven, CT, 
      06520, USA.
FAU - Yang, Shengtao
AU  - Yang S
AD  - Department of Neuroscience, Yale University School of Medicine, New Haven, CT, 
      06520, USA.
FAU - Lowet, Adam S
AU  - Lowet AS
AD  - Department of Neuroscience, Yale University School of Medicine, New Haven, CT, 
      06520, USA.
FAU - Datta, Dibyadeep
AU  - Datta D
AD  - Department of Neuroscience, Yale University School of Medicine, New Haven, CT, 
      06520, USA.
FAU - Duque, Alvaro
AU  - Duque A
AD  - Department of Neuroscience, Yale University School of Medicine, New Haven, CT, 
      06520, USA.
FAU - Arnsten, Amy Ft
AU  - Arnsten AF
AD  - Department of Neuroscience, Yale University School of Medicine, New Haven, CT, 
      06520, USA.
FAU - Wang, Min
AU  - Wang M
AD  - Department of Neuroscience, Yale University School of Medicine, New Haven, CT, 
      06520, USA.
LA  - eng
GR  - R01 MH093354/MH/NIMH NIH HHS/United States
GR  - R01 MH113257/MH/NIMH NIH HHS/United States
PT  - Journal Article
DEP - 20210712
PL  - Netherlands
TA  - Curr Res Neurobiol
JT  - Current research in neurobiology
JID - 101778135
PMC - PMC8794314
MID - NIHMS1771448
OTO - NOTNLM
OT  - Acetylcholine
OT  - Muscarinic m1 receptor
OT  - NMDA receptor
OT  - Prefrontal cortex
OT  - Working memory
OT  - dlPFC
COIS- Declaration of competing interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2022/02/01 06:00
MHDA- 2022/02/01 06:01
PMCR- 2021/07/09
CRDT- 2022/01/31 06:04
PHST- 2022/01/31 06:04 [entrez]
PHST- 2022/02/01 06:00 [pubmed]
PHST- 2022/02/01 06:01 [medline]
PHST- 2021/07/09 00:00 [pmc-release]
AID - 100016 [pii]
AID - 10.1016/j.crneur.2021.100016 [doi]
PST - ppublish
SO  - Curr Res Neurobiol. 2021;2:100016. doi: 10.1016/j.crneur.2021.100016. Epub 2021 
      Jul 12.