A novel role for the lateral habenula in fear learning.

TitleA novel role for the lateral habenula in fear learning.
Publication TypeJournal Article
Year of Publication2022
AuteursSachella, TE, Ihidoype, MR, Proulx, CD, Pafundo, DE, Medina, JH, Mendez, P, Piriz, J
JournalNeuropsychopharmacology
Date Published2022 Feb 25
ISSN1740-634X
Abstract

Fear is an extreme form of aversion that underlies pathological conditions such as panic or phobias. Fear conditioning (FC) is the best-understood model of fear learning. In FC the context and a cue are independently associated with a threatening unconditioned stimulus (US). The lateral habenula (LHb) is a general encoder of aversion. However, its role in fear learning remains poorly understood. Here we studied in rats the role of the LHb in FC using optogenetics and pharmacological tools. We found that inhibition or activation of the LHb during entire FC training impaired both cued and contextual FC. In contrast, optogenetic inhibition of the LHb restricted to cue and US presentation impaired cued but not contextual FC. In either case, simultaneous activation of contextual and cued components of FC, by the presentation of the cue in the training context, recovered the conditioned fear response. Our results support the notion that the LHb is required for the formation of independent contextual and cued fear memories, a previously uncharacterized function for this structure, that could be critical in fear generalization.

DOI10.1038/s41386-022-01294-5
Alternate JournalNeuropsychopharmacology
PubMed ID35217797
Grant ListPICT 2016-0034 / / Ministry of Science, Technology and Productive Innovation, Argentina | Agencia Nacional de Promoción Científica y Tecnológica (National Agency for Science and Technology, Argentina) /
PICT 2015-2609 / / Ministry of Science, Technology and Productive Innovation, Argentina | Agencia Nacional de Promoción Científica y Tecnológica (National Agency for Science and Technology, Argentina) /
PICT 2017-4594 / / Ministry of Science, Technology and Productive Innovation, Argentina | Agencia Nacional de Promoción Científica y Tecnológica (National Agency for Science and Technology, Argentina) /
COOPA20198 / / Ministry of Economy and Competitiveness | Consejo Superior de Investigaciones Científicas (Spanish National Research Council) /
Young Investigator Award 2015 (#23861) / / Brain and Behavior Research Foundation (Brain & Behavior Research Foundation) /