Article abstract


Nature Neuroscience 12, 190 - 199 (2009)
Published online: 25 January 2009 | doi:10.1038/nn.2245

Dopamine modulates an mGluR5-mediated depolarization underlying prefrontal persistent activity

Kyriaki Sidiropoulou1,6, Fang-Min Lu2, Melissa A Fowler2, Rui Xiao3, Christopher Phillips2, Emin D Ozkan2, Michael X Zhu3, Francis J White4,5 & Donald C Cooper2


The intrinsic properties of neurons that enable them to maintain depolarized, persistently activated states in the absence of sustained input are poorly understood. In short-term memory tasks, individual prefrontal cortical (PFC) neurons can maintain persistent action potential output during delay periods between informative cues and behavioral responses. Dopamine and drugs of abuse alter PFC function and working memory, possibly by modulating intrinsic neuronal properties. Here we used patch-clamp recording of layer 5 PFC pyramidal neurons to identify a postsynaptic depolarization that was evoked by action potential bursts and mediated by metabotropic glutamate receptor 5 (mGluR5). This depolarization occurred in the absence of recurrent synaptic activity and was reduced by a dopamine D1 receptor (D1R) protein kinase A pathway. After behavioral sensitization to cocaine, the depolarization was substantially diminished and D1R modulation was lost. We propose that burst-evoked intrinsic depolarization is a form of short-term cellular memory that is modulated by dopamine and cocaine experience.

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  1. Department of Neuroscience, Rosalind Franklin University of Health and Science/Chicago Medical School, 3333 Green Bay Road, North Chicago, Illinois 60064, USA.
  2. Department of Psychiatry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9070, USA.
  3. Department of Neuroscience and Center for Molecular Neurobiology, Ohio State University, 206 Rightmire Hall, 1060 Carmack Road, Columbus, Ohio 43210, USA.
  4. Department of Cellular and Molecular Pharmacology, Rosalind Franklin University of Health and Science/Chicago Medical School, 3333 Green Bay Road, North Chicago, Illinois 60064, USA.
  5. Deceased.
  6. Present address: Computational Biology Lab, Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology–Hellas, Vassilika Vouton, GR71110, Greece.

Correspondence to: Donald C Cooper2 e-mail: don.cooper@live.com



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