title: Activity in prelimbic cortex subserves fear memory reconsolidation over time.
abstract: The prelimbic cortex has been implicated in the consolidation of previously learned fear. Herein, we report that temporarily inactivating this medial prefrontal cortex subregion with the GABAA agonist muscimol (4.0 nmol in 0.2 μL per hemisphere) was able to equally disrupt 1-, 7-, and 21-d-old contextual fear memories after their brief retrieval in rats. In all cases, this effect was prevented when memory reactivation was omitted. These results indicate that recent and remote fear memories are susceptible to reconsolidation blockade induced by prelimbic cortex inactivation. It was also demonstrated that the disrupting effect of prelimbic cortex inactivation on fear memory persisted over 11 d, and did not show extinction-related features, such as reinstatement. Infusing the same dose and volume of muscimol bilaterally into the infralimbic cortex after brief retrieval/reactivation of the fear memory did not disrupt it, as seen in prelimbic cortex-inactivated animals. The expression of Zif268/Egr1, the product of an immediate early gene related to memory reconsolidation, was also less pronounced in the infralimbic cortex than in prelimbic cortex following memory retrieval/reactivation. Altogether, the present findings highlight that activity in the prelimbic cortex may reestablish reactivated aversive memories and, therefore, contribute to their maintenance over time.
authors.affiliation: Department of Pharmacology, Federal University of Santa Catarina, Florianópolis, Santa Catarina 88049-900, Brazil.
authors.forename: Cristina A J
authors.initials: CA
authors.lastname: Stern
authors.forename: Lucas
authors.initials: L
authors.lastname: Gazarini
authors.forename: Ana C
authors.initials: AC
authors.lastname: Vanvossen
authors.forename: Mayara S
authors.initials: MS
authors.lastname: Hames
authors.forename: Leandro J
authors.initials: LJ
authors.lastname: Bertoglio
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D051766:Early Growth Response Protein 1 / Q000378:metabolism; D005108:Extinction, Psychological / Q000187:drug effects; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D007839:Functional Laterality; D058785:GABA-A Receptor Agonists / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D009118:Muscimol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D058785:GABA-A Receptor Agonists; D009118:Muscimol