Silverstein, Shana Elyse; (2021) Observational fear learning: From mouse to man. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Observational fear learning (OFL) is a means of conveying threatening information to another and demonstrates how social organisms learn from environmental interactions to promote safety without exposure to harm. This thesis was conducted with the aim of advancing understanding of the mechanisms underlying OFL in a behaviourally translational manner in mice and humans. In Chapter 2, development and characterization of a cued-OFL task for mice is described. Mice form a robust and lasting stimulus specific fear memory through observation of a distressed conspecific that does not produce a phenotype of generalized anxiety nor alterations in socialization. In Chapter 3, anatomical interrogation of cortico-limbic-mid-brain regions and pathways of importance for direct fear learning (DFL) and social learning are identified as potential components of the neural network subserving OFL. In Chapter 4, the functional circuitry of OFL is studied using in vivo optogenetics and Ca2+ imaging via fibre photometry to reveal a causal role of the ventral hippocampus (vHPC) in constraining prelimbic (PL) projections to the lateral/ventrolateral periaqueductal grey (l/vlPAG) to modulate OFL. Study 1 of Chapter 5 addresses the development and validation of an OFL task in humans using reinforcement learning framework and computational modelling. OFL was best characterized by a single learning rate for both high- and low-shock associated stimuli (CS). Moreover, model parameters described participant OFL as not heavily influenced by recent prediction errors and valuation of the CSs was updated relatively slowly. Study 2 of Chapter 5 investigates the relationship of dispositional traits commonly associated with fear, namely anxiety and psychopathy, on individual differences in OFL. Besides a modest association between trait anxiety and prediction response time, limitations with the OFL task and deployment on an online platform were suboptimal for engaging these relationships. Together, these findings provide a complementary approach to characterize OFL in mice and humans.

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