Abstract

Memories about aversive events that elicit fear can imbue fear to other stimuli. This is studied using Pavlovian higher-order fear conditioning. A stimulus that is directly paired with an aversive outcome (i.e., Pavlovian first-order fear conditioning) can support learning about another stimulus (i.e., Pavlovian higher-order fear conditioning). That is, by virtue of its links with a first- order stimulus (i.e., S1), a higher-order stimulus (i.e., S2) controls behaviour by eliciting conditioned defensive responses. This occurs in two ways: either S2 is paired with S1 before the latter is paired with an outcome (i.e., foot shock) as exemplified in sensory preconditioning (SPC), or after S1 is paired with an outcome as exemplified in second-order conditioning (SOC). Reduction in fear to S1 by presenting it in the absence of the shock transfers to sensory preconditioned but not to second-order conditioned fear, showing that two types of fear are supported by distinct behavioural (and neural) structures.
Extensive work investigated the neural substrates underlying first-order fear conditioning, while our understanding of the neural structures mediating higher-order fear conditioning is still relatively limited. The present thesis investigated the role of some of the neural substrates that support sensory preconditioning and second-order conditioning. In Chapter 4 we confirmed that SPC but not SOC required the integrity of first-order fear and provided neural evidence for this dissociation using a chemogenetic approach to delete first-order fear memory, which disrupted SPC but not SOC. In Chapter 5 we investigated the role of lOFC in regulating the expression of both types of fear and showed that lOFC inactivation prior to test disrupted SPC but enhanced SOC. In Chapter 6 we identified the neuronal ensembles that are activated by SPC and SOC in the BLA, a region critical for the expression of fear to SPC and SOC, and showed that a subset of these ensembles showed projections to the lOFC. These projections, when silenced disrupted both types of fear. Lastly, we silenced lOFC input to the BLA and showed that this pathway is crucial for SPC but not SOC. Our findings delineate neurobiological structures differentially supporting SPC and SOC types of fear and characterize the role of lOFC in the fear circuit.