The role of ventral striatal cAMP signaling in stress-induced behaviors

Florian Plattner; Kanehiro Hayashi; Adan Hernández; David R. Benavides; Tara C. Tassin; Chunfeng Tan; Jonathan Day; Maggy W. Fina; Eunice Y. Yuen; Zhen Yan; Matthew S. Goldberg; Angus C. Nairn; Paul Greengard; Eric J. Nestler; Ronald Taussig; Akinori Nishi; Miles D. Houslay; James A. Bibb

doi:10.1038/nn.4066

The role of ventral striatal cAMP signaling in stress-induced behaviors

Florian Plattner, Kanehiro Hayashi, Adan Hernández, David R. Benavides, Tara C. Tassin, Chunfeng Tan, Jonathan Day, Maggy W. Fina, Eunice Y. Yuen, Zhen Yan, Matthew S. Goldberg, Angus C. Nairn, Paul Greengard, Eric J. Nestler, Ronald Taussig, Akinori Nishi, Miles D. Houslay, James A. Bibb

Research output: Contribution to journal › Article › peer-review

62 Scopus citations

Abstract

The cAMP and cAMP-dependent protein kinase A (PKA) signaling cascade is a ubiquitous pathway acting downstream of multiple neuromodulators. We found that the phosphorylation of phosphodiesterase-4 (PDE4) by cyclin-dependent protein kinase 5 (Cdk5) facilitated cAMP degradation and homeostasis of cAMP/PKA signaling. In mice, loss of Cdk5 throughout the forebrain elevated cAMP levels and increased PKA activity in striatal neurons, and altered behavioral responses to acute or chronic stressors. Ventral striatum-or D1 dopamine receptor-specific conditional knockout of Cdk5, or ventral striatum infusion of a small interfering peptide that selectively targeted the regulation of PDE4 by Cdk5, produced analogous effects on stress-induced behavioral responses. Together, our results demonstrate that altering cAMP signaling in medium spiny neurons of the ventral striatum can effectively modulate stress-induced behavioral states. We propose that targeting the Cdk5 regulation of PDE4 could be a new therapeutic approach for clinical conditions associated with stress, such as depression.

Original language	English (US)
Pages (from-to)	1094-1100
Number of pages	7
Journal	Nature neuroscience
Volume	18
Issue number	8
DOIs	https://doi.org/10.1038/nn.4066
State	Published - Aug 30 2015

ASJC Scopus subject areas

General Neuroscience

Access to Document

10.1038/nn.4066

Cite this

Plattner, F., Hayashi, K., Hernández, A., Benavides, D. R., Tassin, T. C., Tan, C., Day, J., Fina, M. W., Yuen, E. Y., Yan, Z., Goldberg, M. S., Nairn, A. C., Greengard, P., Nestler, E. J., Taussig, R., Nishi, A., Houslay, M. D., & Bibb, J. A. (2015). The role of ventral striatal cAMP signaling in stress-induced behaviors. Nature neuroscience, 18(8), 1094-1100. https://doi.org/10.1038/nn.4066

Plattner, F, Hayashi, K, Hernández, A, Benavides, DR, Tassin, TC, Tan, C, Day, J, Fina, MW, Yuen, EY, Yan, Z, Goldberg, MS, Nairn, AC, Greengard, P, Nestler, EJ, Taussig, R, Nishi, A, Houslay, MD & Bibb, JA 2015, 'The role of ventral striatal cAMP signaling in stress-induced behaviors', Nature neuroscience, vol. 18, no. 8, pp. 1094-1100. https://doi.org/10.1038/nn.4066

@article{1917f129c1b04b4ab331c1ae37036465,

title = "The role of ventral striatal cAMP signaling in stress-induced behaviors",

abstract = "The cAMP and cAMP-dependent protein kinase A (PKA) signaling cascade is a ubiquitous pathway acting downstream of multiple neuromodulators. We found that the phosphorylation of phosphodiesterase-4 (PDE4) by cyclin-dependent protein kinase 5 (Cdk5) facilitated cAMP degradation and homeostasis of cAMP/PKA signaling. In mice, loss of Cdk5 throughout the forebrain elevated cAMP levels and increased PKA activity in striatal neurons, and altered behavioral responses to acute or chronic stressors. Ventral striatum-or D1 dopamine receptor-specific conditional knockout of Cdk5, or ventral striatum infusion of a small interfering peptide that selectively targeted the regulation of PDE4 by Cdk5, produced analogous effects on stress-induced behavioral responses. Together, our results demonstrate that altering cAMP signaling in medium spiny neurons of the ventral striatum can effectively modulate stress-induced behavioral states. We propose that targeting the Cdk5 regulation of PDE4 could be a new therapeutic approach for clinical conditions associated with stress, such as depression.",

author = "Florian Plattner and Kanehiro Hayashi and Adan Hern{\'a}ndez and Benavides, {David R.} and Tassin, {Tara C.} and Chunfeng Tan and Jonathan Day and Fina, {Maggy W.} and Yuen, {Eunice Y.} and Zhen Yan and Goldberg, {Matthew S.} and Nairn, {Angus C.} and Paul Greengard and Nestler, {Eric J.} and Ronald Taussig and Akinori Nishi and Houslay, {Miles D.} and Bibb, {James A.}",

year = "2015",

month = aug,

day = "30",

doi = "10.1038/nn.4066",

language = "English (US)",

volume = "18",

pages = "1094--1100",

journal = "Nature neuroscience",

issn = "1097-6256",

publisher = "Nature Publishing Group",

number = "8",

}

TY - JOUR

T1 - The role of ventral striatal cAMP signaling in stress-induced behaviors

AU - Plattner, Florian

AU - Hayashi, Kanehiro

AU - Hernández, Adan

AU - Benavides, David R.

AU - Tassin, Tara C.

AU - Tan, Chunfeng

AU - Day, Jonathan

AU - Fina, Maggy W.

AU - Yuen, Eunice Y.

AU - Yan, Zhen

AU - Goldberg, Matthew S.

AU - Nairn, Angus C.

AU - Greengard, Paul

AU - Nestler, Eric J.

AU - Taussig, Ronald

AU - Nishi, Akinori

AU - Houslay, Miles D.

AU - Bibb, James A.

PY - 2015/8/30

Y1 - 2015/8/30

N2 - The cAMP and cAMP-dependent protein kinase A (PKA) signaling cascade is a ubiquitous pathway acting downstream of multiple neuromodulators. We found that the phosphorylation of phosphodiesterase-4 (PDE4) by cyclin-dependent protein kinase 5 (Cdk5) facilitated cAMP degradation and homeostasis of cAMP/PKA signaling. In mice, loss of Cdk5 throughout the forebrain elevated cAMP levels and increased PKA activity in striatal neurons, and altered behavioral responses to acute or chronic stressors. Ventral striatum-or D1 dopamine receptor-specific conditional knockout of Cdk5, or ventral striatum infusion of a small interfering peptide that selectively targeted the regulation of PDE4 by Cdk5, produced analogous effects on stress-induced behavioral responses. Together, our results demonstrate that altering cAMP signaling in medium spiny neurons of the ventral striatum can effectively modulate stress-induced behavioral states. We propose that targeting the Cdk5 regulation of PDE4 could be a new therapeutic approach for clinical conditions associated with stress, such as depression.

AB - The cAMP and cAMP-dependent protein kinase A (PKA) signaling cascade is a ubiquitous pathway acting downstream of multiple neuromodulators. We found that the phosphorylation of phosphodiesterase-4 (PDE4) by cyclin-dependent protein kinase 5 (Cdk5) facilitated cAMP degradation and homeostasis of cAMP/PKA signaling. In mice, loss of Cdk5 throughout the forebrain elevated cAMP levels and increased PKA activity in striatal neurons, and altered behavioral responses to acute or chronic stressors. Ventral striatum-or D1 dopamine receptor-specific conditional knockout of Cdk5, or ventral striatum infusion of a small interfering peptide that selectively targeted the regulation of PDE4 by Cdk5, produced analogous effects on stress-induced behavioral responses. Together, our results demonstrate that altering cAMP signaling in medium spiny neurons of the ventral striatum can effectively modulate stress-induced behavioral states. We propose that targeting the Cdk5 regulation of PDE4 could be a new therapeutic approach for clinical conditions associated with stress, such as depression.

UR - http://www.scopus.com/inward/record.url?scp=84938417105&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84938417105&partnerID=8YFLogxK

U2 - 10.1038/nn.4066

DO - 10.1038/nn.4066

M3 - Article

C2 - 26192746

AN - SCOPUS:84938417105

SN - 1097-6256

VL - 18

SP - 1094

EP - 1100

JO - Nature neuroscience

JF - Nature neuroscience

IS - 8

ER -

The role of ventral striatal cAMP signaling in stress-induced behaviors

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this