title: Removal of perineuronal nets in the medial prefrontal cortex impairs the acquisition and reconsolidation of a cocaine-induced conditioned place preference memory.
abstract: Pyramidal neurons in the medial prefrontal cortex (mPFC) critically contribute to cocaine-seeking behavior in humans and rodents. Activity of these neurons is significantly modulated by GABAergic, parvalbumin-containing, fast-spiking interneurons, the majority of which are enveloped by specialized structures of extracellular matrix called perineuronal nets (PNNs), which are integral to the maintenance of many types of plasticity. Using a conditioned place preference (CPP) procedure, we found that removal of PNNs primarily from the prelimbic region of the mPFC of adult, male, Sprague Dawley rats impaired the acquisition and reconsolidation of a cocaine-induced CPP memory. This impairment was accompanied by a decrease in the number of c-Fos-positive cells surrounded by PNNs. Following removal of PNNs, the frequency of inhibitory currents in mPFC pyramidal neurons was decreased; but following cocaine-induced CPP, both frequency and amplitude of inhibitory currents were decreased. Our findings suggest that cocaine-induced plasticity is impaired by removal of prelimbic mPFC PNNs and that PNNs may be a therapeutic target for disruption of cocaine CPP memories.
authors.affiliation: Department of Integrative Physiology and Neuroscience, Washington State University, Vancouver, Washington 98686.
authors.forename: Megan
authors.initials: M
authors.lastname: Slaker
authors.affiliation: Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, Washington 99164.
authors.forename: Lynn
authors.initials: L
authors.lastname: Churchill
authors.affiliation: Department of Integrative Physiology and Neuroscience, Washington State University, Vancouver, Washington 98686.
authors.forename: Ryan P
authors.initials: RP
authors.lastname: Todd
authors.affiliation: Department of Integrative Physiology and Neuroscience, Washington State University, Vancouver, Washington 98686.
authors.forename: Jordan M
authors.initials: JM
authors.lastname: Blacktop
authors.affiliation: Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, Oregon 97239.
authors.forename: Damian G
authors.initials: DG
authors.lastname: Zuloaga
authors.affiliation: Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, Oregon 97239, Departments of Neurology and Radiation Medicine, Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, Portland, Oregon 97239, and.
authors.forename: Jacob
authors.initials: J
authors.lastname: Raber
authors.affiliation: School of Pharmacy and Department of Neuroscience, University of Wyoming, Laramie, Wyoming 82071.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Darling
authors.affiliation: School of Pharmacy and Department of Neuroscience, University of Wyoming, Laramie, Wyoming 82071.
authors.forename: Travis E
authors.initials: TE
authors.lastname: Brown
authors.affiliation: Department of Integrative Physiology and Neuroscience, Washington State University, Vancouver, Washington 98686, sorg@vetmed.wsu.edu.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Sorg
mesh_terms: D000818:Animals; D001245:Association Learning / Q000187:drug effects; D001930:Brain Injuries / Q000150:complications* / Q000473:pathology; D019765:Chondroitin ABC Lyase / Q000008:administration & dosage; D003042:Cocaine / Q000008:administration & dosage; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology; D008297:Male; D008569:Memory Disorders / Q000209:etiology*; D018613:Microscopy, Confocal; D009415:Nerve Net / Q000187:drug effects / Q000293:injuries / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D037121:Plant Lectins / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects / Q000473:pathology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D034781:Receptors, N-Acetylglucosamine / Q000378:metabolism; D013997:Time Factors
chemical_list: D018765:Dopamine Uptake Inhibitors; D009419:Nerve Tissue Proteins; D037121:Plant Lectins; D016760:Proto-Oncogene Proteins c-fos; D034781:Receptors, N-Acetylglucosamine; C040129:wisteria lectin; D019765:Chondroitin ABC Lyase; D003042:Cocaine
keywords: cocaine; conditioned place preference; memory; perineuronal net