Second-order fear conditioning involves formation of competing stimulus-danger and stimulus-safety associations. 2023

Justine Fam, and Billy Chieng, and R Frederick Westbrook, and Vincent Laurent, and Nathan M Holmes
School of Psychology, University of New South Wales, Sydney, NSW 2052, Australia.

How do animals process experiences that provide contradictory information? The present study addressed this question using second-order fear conditioning in rats. In second-order conditioning, rats are conditioned to fear a stimulus, S1, through its pairings with foot-shock (stage 1); and some days later, a second stimulus, S2, through its pairings with the already-conditioned S1 (stage 2). However, as foot-shock is never presented during conditioning to S2, we hypothesized that S2 simultaneously encodes 2 contradictory associations: one that drives fear to S2 (S2-danger) and another that reflects the absence of the expected unconditioned stimulus and partially masks that fear (e.g. S2-safety). We tested this hypothesis by manipulating the substrates of danger and safety learning in the brain (using a chemogenetic approach) and assessing the consequences for second-order fear to S2. Critically, silencing activity in the basolateral amygdala (important for danger learning) reduced fear to S2, whereas silencing activity in the infralimbic cortex (important for safety learning) enhanced fear to S2. These bidirectional changes are consistent with our hypothesis that second-order fear conditioning involves the formation of competing S2-danger and S2-safety associations. More generally, they show that a single set of experiences can produce contradictory associations and that the brain resolves the contradiction by encoding these associations in distinct brain regions.

UI MeSH Term Description Entries
D007858 Learning Relatively permanent change in behavior that is the result of past experience or practice. The concept includes the acquisition of knowledge. Phenomenography
D003214 Conditioning, Classical Learning that takes place when a conditioned stimulus is paired with an unconditioned stimulus. Reflex, Conditioned,Classical Conditioning,Classical Conditionings,Conditioned Reflex,Conditionings, Classical
D003216 Conditioning, Operant Learning situations in which the sequence responses of the subject are instrumental in producing reinforcement. When the correct response occurs, which involves the selection from among a repertoire of responses, the subject is immediately reinforced. Instrumental Learning,Learning, Instrumental,Operant Conditioning,Conditionings, Operant,Instrumental Learnings,Learnings, Instrumental,Operant Conditionings
D005239 Fear The affective response to an actual current external danger which subsides with the elimination of the threatening condition. Threat Cues,Threat Sensitivity,Cue, Threat,Fears,Sensitivity, Threat,Threat Cue,Threat Sensitivities
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D066272 Basolateral Nuclear Complex A set of amygdalar nuclei bordered laterally by the EXTERNAL CAPSULE and medially by the CENTRAL AMYGDALOID NUCLEUS. Amygdaloid Basolateral Complex,Basolateral Amygdala,Basolateral Amygdaloid Nucleus,Accessory Basal Amygdaloid Nucleus,Accessory Basal Nucleus,Basal Amygdaloid Nucleus,Basal Nucleus of the Amygdala,Basolateral Nuclear Group,Deep Nuclei, Amygdala,Deep Nuclei, Amygdaloid,Lateral Amygdaloid Nucleus,Lateral Nucleus of Amygdala,Lateral Principal Nucleus of Amygdala,Paralaminar Nucleus,Amygdala Deep Nuclei,Amygdala Deep Nucleus,Amygdala Lateral Nucleus,Amygdala, Basolateral,Amygdaloid Basolateral Complices,Amygdaloid Deep Nuclei,Amygdaloid Deep Nucleus,Amygdaloid Nucleus, Basal,Amygdaloid Nucleus, Basolateral,Amygdaloid Nucleus, Lateral,Basal Nucleus, Accessory,Basolateral Amygdalas,Basolateral Complex, Amygdaloid,Basolateral Nuclear Complices,Basolateral Nuclear Groups,Deep Nucleus, Amygdala,Deep Nucleus, Amygdaloid,Nuclear Complex, Basolateral,Nuclear Complices, Basolateral,Nuclear Group, Basolateral,Nuclear Groups, Basolateral,Nucleus, Accessory Basal,Nucleus, Basolateral Amygdaloid

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