UCLA

How do we decide what to do when faced with an ambiguous situation with only partial information available? Considerable evidence suggests that we apply inferential reasoning strategies that draw on our past experiences to generate predictions about the new circumstance. Importantly, the ability to make decisions when faced with uncertainty declines disproportionately with age, particularly among clinical populations suffering from cognitive decline, such as in Alzheimer's disease. However the causes of these deficits remain poorly understood and effective treatment methods have yet to be identified. In this thesis, a series of experiments were conducted to develop a non-human model of decision-making under ambiguity. Chapter 1 serves as a review of relevant empirical work establishing that non-human animals are capable of learning about events that are physically absent from a situation. Chapter 2 demonstrated that rats discriminate between the ambiguous and explicit absence of a relevant event. Importantly, the ability to respond sensitively to the ambiguous event was dependent on the type of task the rats had prior to the test. Rats that had learned a complex discrimination responded differently when a cue was ambiguously absent compared to when it was explicitly absent during test, while rats that had learned a simpler discrimination did not. Chapter 3 examined the necessary and sufficient features of cue experience that contribute to this behavioral sensitivity to ambiguous situations and suggested that elements of solution strategy engaged during these experiences determine the approach to ambiguity. Chapter 4 utilized the rat model of decision-making under ambiguity established in Chapters 2 and 3 to examine the underlying neural mechanisms mediating this ability. The hippocampus and, to a lesser extent, the prefrontal cortex were found to be critically involved. Specifically, cholinergic modulation within the hippocampus was necessary for rats to utilize inferential reasoning-like strategies in the ambiguous situation. This finding parallels the discovery that cholinergic function and the hippocampus undergo significant atrophy in aging populations, especially among Alzheimer's patients. Additionally, it was discovered that different patterns of neural activity within the hippocampus and prefrontal cortex were engaged when rats utilized this reasoning strategy under ambiguity compared to rats that did not experience an ambiguous test situation or rats that failed to exercise reasoning when faced with ambiguity. The ability to retrieve an image (representation) of the ambiguous event was determined to be critically important for inferential reasoning abilities in Chapter 5. Collectively, the results suggest that experience with ambiguous cues (that signal two competing outcomes) facilitates the use of imagery and guides decision-making in novel and ambiguous situations. This thesis has the potential to inform learning theories and the development of behavioral and pharmacological interventions to enhance these abilities or prevent them from erosion in humans.