Muscarinic M1 Receptors Modulate Working Memory Performance and Activity via KCNQ Potassium Channels in the Primate Prefrontal Cortex.
KCNQ
M1
acetylcholine
aging
cholinergic
dorsolateral prefrontal cortex
muscarinic
prefrontal cortex
schizophrenia
working memory
Journal
Neuron
ISSN: 1097-4199
Titre abrégé: Neuron
Pays: United States
ID NLM: 8809320
Informations de publication
Date de publication:
20 05 2020
20 05 2020
Historique:
received:
18
11
2019
revised:
21
01
2020
accepted:
25
02
2020
pubmed:
21
3
2020
medline:
22
8
2020
entrez:
21
3
2020
Statut:
ppublish
Résumé
Working memory relies on the dorsolateral prefrontal cortex (dlPFC), where microcircuits of pyramidal neurons enable persistent firing in the absence of sensory input, maintaining information through recurrent excitation. This activity relies on acetylcholine, although the molecular mechanisms for this dependence are not thoroughly understood. This study investigated the role of muscarinic M1 receptors (M1Rs) in the dlPFC using iontophoresis coupled with single-unit recordings from aging monkeys with naturally occurring cholinergic depletion. We found that M1R stimulation produced an inverted-U dose response on cell firing and behavioral performance when given systemically to aged monkeys. Immunoelectron microscopy localized KCNQ isoforms (Kv7.2, Kv7.3, and Kv7.5) on layer III dendrites and spines, similar to M1Rs. Iontophoretic manipulation of KCNQ channels altered cell firing and reversed the effects of M1R compounds, suggesting that KCNQ channels are one mechanism for M1R actions in the dlPFC. These results indicate that M1Rs may be an appropriate target to treat cognitive disorders with cholinergic alterations.
Identifiants
pubmed: 32197063
pii: S0896-6273(20)30153-7
doi: 10.1016/j.neuron.2020.02.030
pmc: PMC7244366
mid: NIHMS1572773
pii:
doi:
Substances chimiques
KCNQ Potassium Channels
0
Receptor, Muscarinic M1
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
649-661.e4Subventions
Organisme : NIMH NIH HHS
ID : R01 MH093354
Pays : United States
Organisme : NIDA NIH HHS
ID : R37 DA023999
Pays : United States
Organisme : NIAAA NIH HHS
ID : RL1 AA017536
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
Références
eNeuro. 2018 Nov 15;5(5):
pubmed: 30713994
Cereb Cortex. 2007 Jan;17(1):221-9
pubmed: 16481562
J Neurophysiol. 1989 Feb;61(2):331-49
pubmed: 2918358
Bipolar Disord. 2015 Mar;17(2):150-9
pubmed: 25041603
Am J Psychiatry. 2008 Aug;165(8):1040-7
pubmed: 18381905
Neuron. 2002 Aug 1;35(3):507-20
pubmed: 12165472
Neurobiol Aging. 2013 Apr;34(4):1210-20
pubmed: 23158764
Neuropsychopharmacology. 2016 Jan;41(2):598-610
pubmed: 26108886
Genes Brain Behav. 2020 Jan;19(1):e12599
pubmed: 31283873
Neuroscience. 1989;33(3):469-81
pubmed: 2636703
Pharmacol Biochem Behav. 2005 Jul;81(3):575-84
pubmed: 15936063
Neuroreport. 1999 Jun 3;10(8):1779-82
pubmed: 10501574
J Comp Neurol. 2003 Aug 25;463(3):281-302
pubmed: 12820162
J Comp Neurol. 1983 Feb 20;214(2):170-97
pubmed: 6841683
Annu Rev Neurosci. 2013 Jul 8;36:271-94
pubmed: 23841840
Mol Psychiatry. 2002;7(10):1083-91
pubmed: 12476323
J Cogn Neurosci. 2014 Sep;26(9):1981-91
pubmed: 24666128
Pharmacogenomics J. 2007 Apr;7(2):123-32
pubmed: 16733521
Biol Psychiatry. 2012 May 1;71(9):805-13
pubmed: 21816388
Prog Brain Res. 1993;98:61-71
pubmed: 8248538
Neurobiol Aging. 1989 Jan-Feb;10(1):11-9
pubmed: 2569169
J Neurochem. 1981 Oct;37(4):978-84
pubmed: 7320734
J Physiol. 2008 Apr 1;586(7):1781-3
pubmed: 18381340
Science. 1981 Aug 7;213(4508):674-6
pubmed: 7256270
Mol Psychiatry. 2017 Nov;22(11):1615-1625
pubmed: 27502475
Neurobiol Stress. 2019 Jul 26;11:100187
pubmed: 31832507
Cereb Cortex. 2013 Jul;23(7):1643-54
pubmed: 22693343
Nat Rev Neurosci. 2005 Nov;6(11):850-62
pubmed: 16261179
Anat Rec. 1991 Mar;229(3):384-98
pubmed: 2024779
Neuron. 2018 Jun 27;98(6):1256-1268.e4
pubmed: 29887340
PLoS One. 2014 Jan 08;9(1):e84260
pubmed: 24416208
J Comp Physiol Psychol. 1971 Nov;77(2):212-20
pubmed: 5000659
Science. 2004 Oct 29;306(5697):882-4
pubmed: 15514161
Neurobiol Aging. 1988 Jul-Aug;9(4):351-6
pubmed: 3185853
Epilepsia. 2012 Mar;53(3):412-24
pubmed: 22220513
J Comp Neurol. 2012 May 1;520(7):1562-83
pubmed: 22102330
Nat Neurosci. 2011 Nov 06;14(12):1510-2
pubmed: 22057191
Int Rev Neurobiol. 2007;81:41-57
pubmed: 17433917
J Cogn Neurosci. 2005 Sep;17(9):1483-96
pubmed: 16197701
Brain. 1976 Sep;99(3):459-96
pubmed: 11871
Cereb Cortex. 2000 Jan;10(1):82-92
pubmed: 10639398
Expert Opin Investig Drugs. 2016 Oct;25(10):1181-7
pubmed: 27459153
Neuron. 2007 Nov 21;56(4):701-13
pubmed: 18031686
J Neurosci. 2015 Dec 9;35(49):16064-76
pubmed: 26658860
J Neurosci. 2018 Jan 31;38(5):1137-1150
pubmed: 29255006
Anat Rec A Discov Mol Cell Evol Biol. 2006 Jan;288(1):26-35
pubmed: 16342214
Science. 1982 Jul 30;217(4558):408-14
pubmed: 7046051
Nature. 2001 Jun 21;411(6840):953-6
pubmed: 11418860
Annu Rev Pharmacol Toxicol. 2016;56:339-60
pubmed: 26738476
Proc Natl Acad Sci U S A. 2016 Feb 23;113(8):E1089-97
pubmed: 26787867
Arch Gen Psychiatry. 2005 Oct;62(10):1071-80
pubmed: 16203952
Ann Neurol. 1986 Feb;19(2):144-51
pubmed: 3963756
Ann Neurol. 1987 Jul;22(1):31-6
pubmed: 3307603
Neuron. 1995 Mar;14(3):477-85
pubmed: 7695894
Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5194-8
pubmed: 8389473
Am J Hum Genet. 2017 Jul 6;101(1):65-74
pubmed: 28669405
Cell. 2007 Apr 20;129(2):397-410
pubmed: 17448997
Proc Natl Acad Sci U S A. 2013 Jul 16;110(29):12078-83
pubmed: 23818597
Nature. 2011 Jul 27;476(7359):210-3
pubmed: 21796118
Neuroscience. 2003;117(3):577-92
pubmed: 12617964
Neuron. 2013 Feb 20;77(4):736-49
pubmed: 23439125
Biol Psychiatry. 2008 Jul 1;64(1):11-7
pubmed: 18400207
Ther Adv Drug Saf. 2015 Feb;6(1):15-9
pubmed: 25642319
J Neurosci. 2005 Feb 2;25(5):1260-7
pubmed: 15689564
Neurobiol Aging. 1981 Winter;2(4):251-6
pubmed: 6174877
J Neurosci. 2010 Jun 2;30(22):7507-15
pubmed: 20519525
Nature. 1998 Dec 17;396(6712):687-90
pubmed: 9872318
Am J Psychiatry. 1986 Aug;143(8):993-7
pubmed: 3487983
J Neurosci. 1989 Oct;9(10):3568-76
pubmed: 2795141
FASEB J. 1993 Jun;7(9):768-75
pubmed: 8330684
Alzheimers Dement. 2018 May;14(5):680-691
pubmed: 29241829
Neuropsychopharmacology. 2015 Dec;40(13):3053-60
pubmed: 26089183
Epilepsia. 2015 Feb;56(2):e15-20
pubmed: 25524373
Neuron. 2007 Oct 4;56(1):141-54
pubmed: 17920021
J Gen Physiol. 2004 Jun;123(6):663-83
pubmed: 15173220
Nat Neurosci. 2007 Mar;10(3):376-84
pubmed: 17277774
Psychopharmacology (Berl). 2015 May;232(9):1607-17
pubmed: 25373869