title: Distinct Fos-Expressing Neuronal Ensembles in the Ventromedial Prefrontal Cortex Mediate Food Reward and Extinction Memories.
abstract: In operant learning, initial reward-associated memories are thought to be distinct from subsequent extinction-associated memories. Memories formed during operant learning are thought to be stored in "neuronal ensembles." Thus, we hypothesize that different neuronal ensembles encode reward- and extinction-associated memories. Here, we examined prefrontal cortex neuronal ensembles involved in the recall of reward and extinction memories of food self-administration. We first trained rats to lever press for palatable food pellets for 7 d (1 h/d) and then exposed them to 0, 2, or 7 daily extinction sessions in which lever presses were not reinforced. Twenty-four hours after the last training or extinction session, we exposed the rats to either a short 15 min extinction test session or left them in their homecage (a control condition). We found maximal Fos (a neuronal activity marker) immunoreactivity in the ventral medial prefrontal cortex of rats that previously received 2 extinction sessions, suggesting that neuronal ensembles in this area encode extinction memories. We then used the Daun02 inactivation procedure to selectively disrupt ventral medial prefrontal cortex neuronal ensembles that were activated during the 15 min extinction session following 0 (no extinction) or 2 prior extinction sessions to determine the effects of inactivating the putative food reward and extinction ensembles, respectively, on subsequent nonreinforced food seeking 2 d later. Inactivation of the food reward ensembles decreased food seeking, whereas inactivation of the extinction ensembles increased food seeking. Our results indicate that distinct neuronal ensembles encoding operant reward and extinction memories intermingle within the same cortical area.
  
  
  
  A current popular hypothesis is that neuronal ensembles in different prefrontal cortex areas control reward-associated versus extinction-associated memories: the dorsal medial prefrontal cortex (mPFC) promotes reward seeking, whereas the ventral mPFC inhibits reward seeking. In this paper, we use the Daun02 chemogenetic inactivation procedure to demonstrate that Fos-expressing neuronal ensembles mediating both food reward and extinction memories intermingle within the same ventral mPFC area.
authors.affiliation: Behavioral Neuroscience Branch, Intramural Research Program/National Institute on Drug Abuse/National Institutes of Health/Department of Health and Human Services, Baltimore, Maryland 21224.
authors.forename: Brandon L
authors.initials: BL
authors.lastname: Warren
authors.affiliation: Behavioral Neuroscience Branch, Intramural Research Program/National Institute on Drug Abuse/National Institutes of Health/Department of Health and Human Services, Baltimore, Maryland 21224.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Mendoza
authors.affiliation: Behavioral Neuroscience Branch, Intramural Research Program/National Institute on Drug Abuse/National Institutes of Health/Department of Health and Human Services, Baltimore, Maryland 21224.
authors.forename: Fabio C
authors.initials: FC
authors.lastname: Cruz
authors.affiliation: Behavioral Neuroscience Branch, Intramural Research Program/National Institute on Drug Abuse/National Institutes of Health/Department of Health and Human Services, Baltimore, Maryland 21224.
authors.forename: Rodrigo M
authors.initials: RM
authors.lastname: Leao
authors.affiliation: Behavioral Neuroscience Branch, Intramural Research Program/National Institute on Drug Abuse/National Institutes of Health/Department of Health and Human Services, Baltimore, Maryland 21224.
authors.forename: Daniele
authors.initials: D
authors.lastname: Caprioli
authors.affiliation: Behavioral Neuroscience Branch, Intramural Research Program/National Institute on Drug Abuse/National Institutes of Health/Department of Health and Human Services, Baltimore, Maryland 21224.
authors.forename: F Javier
authors.initials: FJ
authors.lastname: Rubio
authors.affiliation: Behavioral Neuroscience Branch, Intramural Research Program/National Institute on Drug Abuse/National Institutes of Health/Department of Health and Human Services, Baltimore, Maryland 21224.
authors.forename: Leslie R
authors.initials: LR
authors.lastname: Whitaker
authors.affiliation: Behavioral Neuroscience Branch, Intramural Research Program/National Institute on Drug Abuse/National Institutes of Health/Department of Health and Human Services, Baltimore, Maryland 21224.
authors.forename: Kylie B
authors.initials: KB
authors.lastname: McPherson
authors.affiliation: Behavioral Neuroscience Branch, Intramural Research Program/National Institute on Drug Abuse/National Institutes of Health/Department of Health and Human Services, Baltimore, Maryland 21224.
authors.forename: Jennifer M
authors.identifier: 0000-0001-5636-4071
authors.initials: JM
authors.lastname: Bossert
authors.affiliation: Behavioral Neuroscience Branch, Intramural Research Program/National Institute on Drug Abuse/National Institutes of Health/Department of Health and Human Services, Baltimore, Maryland 21224.
authors.forename: Yavin
authors.identifier: 0000-0002-8242-3319
authors.initials: Y
authors.lastname: Shaham
authors.affiliation: Behavioral Neuroscience Branch, Intramural Research Program/National Institute on Drug Abuse/National Institutes of Health/Department of Health and Human Services, Baltimore, Maryland 21224 bhope@intra.nida.nih.gov.
authors.forename: Bruce T
authors.initials: BT
authors.lastname: Hope
mesh_terms: D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D003630:Daunorubicin / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology*; D018682:GABA Agents / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D008297:Male; D011939:Mental Recall / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D016761:Oncogene Proteins v-fos / Q000378:metabolism*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D017397:Prefrontal Cortex / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D020318:Rats, Long-Evans; D012201:Reward; D012646:Self Administration; D013997:Time Factors; D050598:Vesicular Glutamate Transport Protein 1 / Q000235:genetics / Q000378:metabolism; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D018682:GABA Agents; C576267:N-(4''-(galactopyranosyl)-3''-nitrobenzyloxycarbonyl)daunomycin; D016761:Oncogene Proteins v-fos; C493466:Slc17a7 protein, rat; C118623:Slc32a1 protein, rat; D050598:Vesicular Glutamate Transport Protein 1; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; D010751:Phosphopyruvate Hydratase; D003630:Daunorubicin
keywords: Daun02 inactivation; RNAscope; food reward; operant conditioning; vmPFC