Cocaine Regulates MEF2 to Control Synaptic and Behavioral Plasticity

Suprabha Pulipparacharuvil, William Renthal, Carly F. Hale, Makoto Taniguchi, Guanghua Xiao, Arvind Kumar, Scott J. Russo, Devanjan Sikder, Colleen M. Dewey, Maya M. Davis, Paul Greengard, Angus C. Nairn, Eric J. Nestler, Christopher W. Cowan

Research output: Contribution to journalArticle

177 Citations (Scopus)

Abstract

Repeated exposure to cocaine causes sensitized behavioral responses and increased dendritic spines on medium spiny neurons of the nucleus accumbens (NAc). We find that cocaine regulates myocyte enhancer factor 2 (MEF2) transcription factors to control these two processes in vivo. Cocaine suppresses striatal MEF2 activity in part through a mechanism involving cAMP, the regulator of calmodulin signaling (RCS), and calcineurin. We show that reducing MEF2 activity in the NAc in vivo is required for the cocaine-induced increases in dendritic spine density. Surprisingly, we find that increasing MEF2 activity in the NAc, which blocks the cocaine-induced increase in dendritic spine density, enhances sensitized behavioral responses to cocaine. Together, our findings implicate MEF2 as a key regulator of structural synapse plasticity and sensitized responses to cocaine and suggest that reducing MEF2 activity (and increasing spine density) in NAc may be a compensatory mechanism to limit long-lasting maladaptive behavioral responses to cocaine.

Original languageEnglish (US)
Pages (from-to)621-633
Number of pages13
JournalNeuron
Volume59
Issue number4
DOIs
StatePublished - Aug 28 2008

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MEF2 Transcription Factors
Neuronal Plasticity
Cocaine
Nucleus Accumbens
Dendritic Spines
Corpus Striatum
Calcineurin
Calmodulin
Synapses
Spine
Transcription Factors
Neurons

Keywords

  • MOLNEURO
  • SIGNALING

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Pulipparacharuvil, S., Renthal, W., Hale, C. F., Taniguchi, M., Xiao, G., Kumar, A., ... Cowan, C. W. (2008). Cocaine Regulates MEF2 to Control Synaptic and Behavioral Plasticity. Neuron, 59(4), 621-633. https://doi.org/10.1016/j.neuron.2008.06.020

Cocaine Regulates MEF2 to Control Synaptic and Behavioral Plasticity. / Pulipparacharuvil, Suprabha; Renthal, William; Hale, Carly F.; Taniguchi, Makoto; Xiao, Guanghua; Kumar, Arvind; Russo, Scott J.; Sikder, Devanjan; Dewey, Colleen M.; Davis, Maya M.; Greengard, Paul; Nairn, Angus C.; Nestler, Eric J.; Cowan, Christopher W.

In: Neuron, Vol. 59, No. 4, 28.08.2008, p. 621-633.

Research output: Contribution to journalArticle

Pulipparacharuvil, S, Renthal, W, Hale, CF, Taniguchi, M, Xiao, G, Kumar, A, Russo, SJ, Sikder, D, Dewey, CM, Davis, MM, Greengard, P, Nairn, AC, Nestler, EJ & Cowan, CW 2008, 'Cocaine Regulates MEF2 to Control Synaptic and Behavioral Plasticity', Neuron, vol. 59, no. 4, pp. 621-633. https://doi.org/10.1016/j.neuron.2008.06.020
Pulipparacharuvil S, Renthal W, Hale CF, Taniguchi M, Xiao G, Kumar A et al. Cocaine Regulates MEF2 to Control Synaptic and Behavioral Plasticity. Neuron. 2008 Aug 28;59(4):621-633. https://doi.org/10.1016/j.neuron.2008.06.020
Pulipparacharuvil, Suprabha ; Renthal, William ; Hale, Carly F. ; Taniguchi, Makoto ; Xiao, Guanghua ; Kumar, Arvind ; Russo, Scott J. ; Sikder, Devanjan ; Dewey, Colleen M. ; Davis, Maya M. ; Greengard, Paul ; Nairn, Angus C. ; Nestler, Eric J. ; Cowan, Christopher W. / Cocaine Regulates MEF2 to Control Synaptic and Behavioral Plasticity. In: Neuron. 2008 ; Vol. 59, No. 4. pp. 621-633.
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