RT Journal Article
SR Electronic
T1 Lateral Habenula Mediates Defensive Responses Only When Threat and Safety Memories Are in Conflict
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0482-20.2021
DO 10.1523/ENEURO.0482-20.2021
VO 8
IS 2
A1 Velazquez-Hernandez, Geronimo
A1 Sotres-Bayon, Francisco
YR 2021
UL http://www.eneuro.org/content/8/2/ENEURO.0482-20.2021.abstract
AB Survival depends on the ability to adaptively react or execute actions based on previous aversive salient experiences. Although lateral habenula (LHb) activity has been broadly implicated in the regulation of aversively motivated responses, it is not clear under which conditions this brain structure is necessary to regulate defensive responses to a threat. To address this issue, we combined pharmacological inactivations with behavioral tasks that involve aversive and appetitive events and evaluated defensive responses in rats. We found that LHb pharmacological inactivation did not affect cued threat conditioning (fear) and extinction (safety) learning and memory, anxiety-like or reward-seeking behaviors. Surprisingly, we found that LHb inactivation abolished reactive defensive responses (tone-elicited freezing) only when threat (conditioning) and safety memories (extinction and latent inhibition) compete during retrieval. Consistently, we found that LHb inactivation impaired active defensive responses [platform-mediated avoidance (PMA)], thereby biasing choice behavior (between avoiding a threat or approaching food) toward reward-seeking responses. Together, our findings suggest that LHb activity mediates defensive responses only when guided by competing threat and safety memories, consequently revealing a previously uncharacterized role for LHb in experience-dependent emotional conflict.