The neural substrates of higher-order conditioning: A review

Sensory preconditioned and second-order conditioned responding are each well-documented. The former occurs in subjects (typically rats) exposed to pairings of two relatively neutral stimuli, S2 and S1, and then to pairings of S1 and a motivationally significant event [an unconditioned stimulus (US)]; the latter occurs when the order of these experiences is reversed with rats being exposed to S1-US pairings and then to S2-S1 pairings. In both cases, rats respond when tested with S2 in a manner appropriate to the affective nature of the US, e.g., approach when the US is appetitive and withdrawal when it is aversive. This paper reviews the neural substrates of sensory preconditioning and second-order conditioning. It identifies commonalities and differences in the substrates of these so-called higher-order conditioning protocols and discusses these commonalities/differences in relation to what is learned. In so doing, the review highlights ways in which these types of conditioning enhance our understanding of how the brain encodes and retrieves different types of information to generate appropriate behavior. •This review examines the neural systems involved in the two types of higher-order conditioning, sensory preconditioning and second-order conditioning.•It brings together studies that have focused on different motivational systems (appetitive and aversive) and used stimuli from a variety of sensory modalities (e.g., flavors, contexts, auditory and visual cues). In doing so, it advances our understanding of: 1) the manner in which motivational states alter processing of simple sensory information; 2) how the brain integrates sensory and motivational information; and 3) the mechanisms by which a network of sensory/motivational stimuli expands to include new information.•The review ultimately provides a set of principled statements regarding these aspects of information processing. The statements highlight the importance of higher-order conditioning protocols when trying to understand complex behaviors in simple (laboratory) environments and simple behaviors in complex (everyday) environments.