title: Revisiting the role of infralimbic cortex in fear extinction with optogenetics.
abstract: Previous rodent studies have implicated the infralimbic (IL) subregion of the medial prefrontal cortex in extinction of auditory fear conditioning. However, these studies used pharmacological inactivation or electrical stimulation techniques, which lack temporal precision and neuronal specificity. Here, we used an optogenetic approach to either activate (with channelrhodopsin) or silence (with halorhodopsin) glutamatergic IL neurons during conditioned tones delivered in one of two phases: extinction training or extinction retrieval. Activating IL neurons during extinction training reduced fear expression and strengthened extinction memory the following day. Silencing IL neurons during extinction training had no effect on within-session extinction, but impaired the retrieval of extinction the following day, indicating that IL activity during extinction tones is necessary for the formation of extinction memory. Surprisingly, however, silencing IL neurons optogenetically or pharmacologically during the retrieval of extinction 1 day or 1 week following extinction training had no effect. Our findings suggest that IL activity during extinction training likely facilitates storage of extinction in target structures, but contrary to current models, IL activity does not appear to be necessary for retrieval of extinction memory.
authors.affiliation: Departments of Psychiatry and Anatomy and Neurobiology, University of Puerto Rico School of Medicine, San Juan, Puerto Rico 00936 fabriciodomonte@gmail.com.
authors.forename: Fabricio H
authors.initials: FH
authors.lastname: Do-Monte
authors.affiliation: Departments of Psychiatry and Anatomy and Neurobiology, University of Puerto Rico School of Medicine, San Juan, Puerto Rico 00936.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Manzano-Nieves
authors.affiliation: Departments of Psychiatry and Anatomy and Neurobiology, University of Puerto Rico School of Medicine, San Juan, Puerto Rico 00936.
authors.forename: Kelvin
authors.identifier: http://orcid.org/0000-0001-9938-1621
authors.initials: K
authors.lastname: Quiñones-Laracuente
authors.affiliation: Departments of Psychiatry and Anatomy and Neurobiology, University of Puerto Rico School of Medicine, San Juan, Puerto Rico 00936.
authors.forename: Liorimar
authors.initials: L
authors.lastname: Ramos-Medina
authors.affiliation: Departments of Psychiatry and Anatomy and Neurobiology, University of Puerto Rico School of Medicine, San Juan, Puerto Rico 00936.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Quirk
mesh_terms: D000200:Action Potentials; D000679:Amygdala / Q000166:cytology / Q000502:physiology*; D000818:Animals; D003214:Conditioning, Classical; D005108:Extinction, Psychological; D005239:Fear; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D062308:Optogenetics; D017397:Prefrontal Cortex / Q000166:cytology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018698:Glutamic Acid
keywords: amygdala; anxiety disorders; fear conditioning; memory; prefrontal cortex; retrieval