title: Dopamine modulates an mGluR5-mediated depolarization underlying prefrontal persistent activity.
abstract: 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.
authors.affiliation: Department of Neuroscience, Rosalind Franklin University of Health and Science/Chicago Medical School, 3333 Green Bay Road, North Chicago, Illinois 60064, USA.
authors.forename: Kyriaki
authors.initials: K
authors.lastname: Sidiropoulou
authors.forename: Fang-Min
authors.initials: FM
authors.lastname: Lu
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Fowler
authors.forename: Rui
authors.initials: R
authors.lastname: Xiao
authors.forename: Christopher
authors.initials: C
authors.lastname: Phillips
authors.forename: Emin D
authors.initials: ED
authors.lastname: Ozkan
authors.forename: Michael X
authors.initials: MX
authors.lastname: Zhu
authors.forename: Francis J
authors.initials: FJ
authors.lastname: White
authors.forename: Donald C
authors.initials: DC
authors.lastname: Cooper
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D017397:Prefrontal Cortex / Q000166:cytology / Q000502:physiology*; D017966:Pyramidal Cells / Q000502:physiology*; D051381:Rats; D064529:Receptor, Metabotropic Glutamate 5; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D013569:Synapses / Q000502:physiology
chemical_list: D018765:Dopamine Uptake Inhibitors; C578936:Grm5 protein, mouse; C578937:Grm5 protein, rat; D064529:Receptor, Metabotropic Glutamate 5; D017447:Receptors, Dopamine D1; D018094:Receptors, Metabotropic Glutamate; D017868:Cyclic AMP-Dependent Protein Kinases; D003042:Cocaine; D002118:Calcium; D004298:Dopamine