Dopamine modulates an mGluR5-mediated depolarization underlying prefrontal persistent activity

Nat Neurosci. 2009 Feb;12(2):190-9. doi: 10.1038/nn.2245. Epub 2009 Jan 25.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology*
  • Animals
  • Calcium / metabolism
  • Cocaine / pharmacology
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Dopamine / metabolism*
  • Dopamine Uptake Inhibitors / pharmacology
  • Male
  • Mice
  • Mice, Knockout
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology
  • Organ Culture Techniques
  • Patch-Clamp Techniques
  • Prefrontal Cortex / cytology
  • Prefrontal Cortex / physiology*
  • Pyramidal Cells / physiology*
  • Rats
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Dopamine D1 / metabolism
  • Receptors, Metabotropic Glutamate / physiology*
  • Synapses / physiology


  • Dopamine Uptake Inhibitors
  • Grm5 protein, mouse
  • Grm5 protein, rat
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Dopamine D1
  • Receptors, Metabotropic Glutamate
  • Cyclic AMP-Dependent Protein Kinases
  • Cocaine
  • Calcium
  • Dopamine