A subpopulation of neuronal M4 muscarinic acetylcholine receptors plays a critical role in modulating dopamine-dependent behaviors

Research output: Contribution to journalJournal articlepeer-review

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A subpopulation of neuronal M4 muscarinic acetylcholine receptors plays a critical role in modulating dopamine-dependent behaviors. / Jeon, Jongrye; Dencker, Ditte; Wörtwein, Gitta; Woldbye, David P D; Cui, Yinghong; Davis, Albert A; Levey, Allan I; Schütz, Günther; Sager, Thomas N; Mørk, Arne; Li, Cuiling; Deng, Chu-Xia; Fink-Jensen, Anders; Wess, Jürgen; Jeon, Jongrye; Nielsen, Ditte Dencker; Wörtwein, Gitta; Woldbye, David P D; Cui, Yinghong; Davis, Albert A; Levey, Allan I; Schütz, Günther; Sager, Thomas N; Mørk, Arne; Li, Cuiling; Deng, Chu-Xia; Fink-Jensen, Anders; Wess, Jürgen.

In: Journal of Neuroscience, Vol. 30, No. 6, 10.02.2010, p. 2396-405.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Jeon, J, Dencker, D, Wörtwein, G, Woldbye, DPD, Cui, Y, Davis, AA, Levey, AI, Schütz, G, Sager, TN, Mørk, A, Li, C, Deng, C-X, Fink-Jensen, A, Wess, J, Jeon, J, Nielsen, DD, Wörtwein, G, Woldbye, DPD, Cui, Y, Davis, AA, Levey, AI, Schütz, G, Sager, TN, Mørk, A, Li, C, Deng, C-X, Fink-Jensen, A & Wess, J 2010, 'A subpopulation of neuronal M4 muscarinic acetylcholine receptors plays a critical role in modulating dopamine-dependent behaviors', Journal of Neuroscience, vol. 30, no. 6, pp. 2396-405. https://doi.org/10.1523/JNEUROSCI.3843-09.2010, https://doi.org/10.1523/JNEUROSCI.3843-09.2010

APA

Jeon, J., Dencker, D., Wörtwein, G., Woldbye, D. P. D., Cui, Y., Davis, A. A., Levey, A. I., Schütz, G., Sager, T. N., Mørk, A., Li, C., Deng, C-X., Fink-Jensen, A., Wess, J., Jeon, J., Nielsen, D. D., Wörtwein, G., Woldbye, D. P. D., Cui, Y., ... Wess, J. (2010). A subpopulation of neuronal M4 muscarinic acetylcholine receptors plays a critical role in modulating dopamine-dependent behaviors. Journal of Neuroscience, 30(6), 2396-405. https://doi.org/10.1523/JNEUROSCI.3843-09.2010, https://doi.org/10.1523/JNEUROSCI.3843-09.2010

Vancouver

Jeon J, Dencker D, Wörtwein G, Woldbye DPD, Cui Y, Davis AA et al. A subpopulation of neuronal M4 muscarinic acetylcholine receptors plays a critical role in modulating dopamine-dependent behaviors. Journal of Neuroscience. 2010 Feb 10;30(6):2396-405. https://doi.org/10.1523/JNEUROSCI.3843-09.2010, https://doi.org/10.1523/JNEUROSCI.3843-09.2010

Author

Jeon, Jongrye ; Dencker, Ditte ; Wörtwein, Gitta ; Woldbye, David P D ; Cui, Yinghong ; Davis, Albert A ; Levey, Allan I ; Schütz, Günther ; Sager, Thomas N ; Mørk, Arne ; Li, Cuiling ; Deng, Chu-Xia ; Fink-Jensen, Anders ; Wess, Jürgen ; Jeon, Jongrye ; Nielsen, Ditte Dencker ; Wörtwein, Gitta ; Woldbye, David P D ; Cui, Yinghong ; Davis, Albert A ; Levey, Allan I ; Schütz, Günther ; Sager, Thomas N ; Mørk, Arne ; Li, Cuiling ; Deng, Chu-Xia ; Fink-Jensen, Anders ; Wess, Jürgen. / A subpopulation of neuronal M4 muscarinic acetylcholine receptors plays a critical role in modulating dopamine-dependent behaviors. In: Journal of Neuroscience. 2010 ; Vol. 30, No. 6. pp. 2396-405.

Bibtex

@article{a0fbcf90430c11df928f000ea68e967b,
title = "A subpopulation of neuronal M4 muscarinic acetylcholine receptors plays a critical role in modulating dopamine-dependent behaviors",
abstract = "Acetylcholine (ACh) regulates many key functions of the CNS by activating cell surface receptors referred to as muscarinic ACh receptors (M(1)-M(5) mAChRs). Like other mAChR subtypes, the M(4) mAChR is widely expressed in different regions of the forebrain. Interestingly, M(4) mAChRs are coexpressed with D(1) dopamine receptors in a specific subset of striatal projection neurons. To investigate the physiological relevance of this M(4) mAChR subpopulation in modulating dopamine-dependent behaviors, we used Cre/loxP technology to generate mutant mice that lack M(4) mAChRs only in D(1) dopamine receptor-expressing cells. The newly generated mutant mice displayed several striking behavioral phenotypes, including enhanced hyperlocomotor activity and increased behavioral sensitization following treatment with psychostimulants. These behavioral changes were accompanied by a lack of muscarinic inhibition of D(1) dopamine receptor-mediated cAMP stimulation in the striatum and an increase in dopamine efflux in the nucleus accumbens. These novel findings demonstrate that a distinct subpopulation of neuronal M(4) mAChRs plays a critical role in modulating several important dopamine-dependent behaviors. Since enhanced central dopaminergic neurotransmission is a hallmark of several severe disorders of the CNS, including schizophrenia and drug addiction, our findings have substantial clinical relevance.",
author = "Jongrye Jeon and Ditte Dencker and Gitta W{\"o}rtwein and Woldbye, {David P D} and Yinghong Cui and Davis, {Albert A} and Levey, {Allan I} and G{\"u}nther Sch{\"u}tz and Sager, {Thomas N} and Arne M{\o}rk and Cuiling Li and Chu-Xia Deng and Anders Fink-Jensen and J{\"u}rgen Wess and Jongrye Jeon and Nielsen, {Ditte Dencker} and Gitta W{\"o}rtwein and Woldbye, {David P D} and Yinghong Cui and Davis, {Albert A} and Levey, {Allan I} and G{\"u}nther Sch{\"u}tz and Sager, {Thomas N} and Arne M{\o}rk and Cuiling Li and Chu-Xia Deng and Anders Fink-Jensen and J{\"u}rgen Wess",
note = "Keywords: Amphetamine; Animals; Antipsychotic Agents; Behavior, Animal; Central Nervous System Stimulants; Cocaine; Corpus Striatum; Cyclic AMP; Dopamine; Mice; Mice, Mutant Strains; Motor Activity; Neurons; Nucleus Accumbens; Receptor, Muscarinic M4; Receptors, Dopamine D1",
year = "2010",
month = feb,
day = "10",
doi = "10.1523/JNEUROSCI.3843-09.2010",
language = "English",
volume = "30",
pages = "2396--405",
journal = "The Journal of neuroscience : the official journal of the Society for Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "6",

}

RIS

TY - JOUR

T1 - A subpopulation of neuronal M4 muscarinic acetylcholine receptors plays a critical role in modulating dopamine-dependent behaviors

AU - Jeon, Jongrye

AU - Dencker, Ditte

AU - Wörtwein, Gitta

AU - Woldbye, David P D

AU - Cui, Yinghong

AU - Davis, Albert A

AU - Levey, Allan I

AU - Schütz, Günther

AU - Sager, Thomas N

AU - Mørk, Arne

AU - Li, Cuiling

AU - Deng, Chu-Xia

AU - Fink-Jensen, Anders

AU - Wess, Jürgen

AU - Jeon, Jongrye

AU - Nielsen, Ditte Dencker

AU - Wörtwein, Gitta

AU - Woldbye, David P D

AU - Cui, Yinghong

AU - Davis, Albert A

AU - Levey, Allan I

AU - Schütz, Günther

AU - Sager, Thomas N

AU - Mørk, Arne

AU - Li, Cuiling

AU - Deng, Chu-Xia

AU - Fink-Jensen, Anders

AU - Wess, Jürgen

N1 - Keywords: Amphetamine; Animals; Antipsychotic Agents; Behavior, Animal; Central Nervous System Stimulants; Cocaine; Corpus Striatum; Cyclic AMP; Dopamine; Mice; Mice, Mutant Strains; Motor Activity; Neurons; Nucleus Accumbens; Receptor, Muscarinic M4; Receptors, Dopamine D1

PY - 2010/2/10

Y1 - 2010/2/10

N2 - Acetylcholine (ACh) regulates many key functions of the CNS by activating cell surface receptors referred to as muscarinic ACh receptors (M(1)-M(5) mAChRs). Like other mAChR subtypes, the M(4) mAChR is widely expressed in different regions of the forebrain. Interestingly, M(4) mAChRs are coexpressed with D(1) dopamine receptors in a specific subset of striatal projection neurons. To investigate the physiological relevance of this M(4) mAChR subpopulation in modulating dopamine-dependent behaviors, we used Cre/loxP technology to generate mutant mice that lack M(4) mAChRs only in D(1) dopamine receptor-expressing cells. The newly generated mutant mice displayed several striking behavioral phenotypes, including enhanced hyperlocomotor activity and increased behavioral sensitization following treatment with psychostimulants. These behavioral changes were accompanied by a lack of muscarinic inhibition of D(1) dopamine receptor-mediated cAMP stimulation in the striatum and an increase in dopamine efflux in the nucleus accumbens. These novel findings demonstrate that a distinct subpopulation of neuronal M(4) mAChRs plays a critical role in modulating several important dopamine-dependent behaviors. Since enhanced central dopaminergic neurotransmission is a hallmark of several severe disorders of the CNS, including schizophrenia and drug addiction, our findings have substantial clinical relevance.

AB - Acetylcholine (ACh) regulates many key functions of the CNS by activating cell surface receptors referred to as muscarinic ACh receptors (M(1)-M(5) mAChRs). Like other mAChR subtypes, the M(4) mAChR is widely expressed in different regions of the forebrain. Interestingly, M(4) mAChRs are coexpressed with D(1) dopamine receptors in a specific subset of striatal projection neurons. To investigate the physiological relevance of this M(4) mAChR subpopulation in modulating dopamine-dependent behaviors, we used Cre/loxP technology to generate mutant mice that lack M(4) mAChRs only in D(1) dopamine receptor-expressing cells. The newly generated mutant mice displayed several striking behavioral phenotypes, including enhanced hyperlocomotor activity and increased behavioral sensitization following treatment with psychostimulants. These behavioral changes were accompanied by a lack of muscarinic inhibition of D(1) dopamine receptor-mediated cAMP stimulation in the striatum and an increase in dopamine efflux in the nucleus accumbens. These novel findings demonstrate that a distinct subpopulation of neuronal M(4) mAChRs plays a critical role in modulating several important dopamine-dependent behaviors. Since enhanced central dopaminergic neurotransmission is a hallmark of several severe disorders of the CNS, including schizophrenia and drug addiction, our findings have substantial clinical relevance.

U2 - 10.1523/JNEUROSCI.3843-09.2010

DO - 10.1523/JNEUROSCI.3843-09.2010

M3 - Journal article

C2 - 20147565

VL - 30

SP - 2396

EP - 2405

JO - The Journal of neuroscience : the official journal of the Society for Neuroscience

JF - The Journal of neuroscience : the official journal of the Society for Neuroscience

SN - 0270-6474

IS - 6

ER -

ID: 19096703