University of Minnesota Ph.D. dissertation. February 2021. Major: Neuroscience. Advisor: David Redish. 1 computer file (PDF); viii, 210 pages.Motivational conflict is thought to take one of three possible forms: approach-approach conflict,avoid-approach conflict, and avoid-avoid conflict. While approach-approach conflict paradigms
have primarily been used to study the neural basis of reward-based decision-making,
avoid-approach conflict paradigms are typically used to model anxiety because they capture the
complex, bivalent nature of most naturalistic environments. Research suggests that
approach-approach conflict initiates a distinct neural algorithm: a hippocampally-mediated
mental simulation of the future that is paired with evaluations of anticipated outcomes. However,
it is unknown whether a similar form of episodic future thinking also occurs during
avoid-approach conflict. Here I present research I have conducted to address this gap in the literature. First, I used apharmacological approach in tandem with a semi-naturalistic avoid-approach predator-inhabited
foraging arena task to show that anxiety-like hesitation behaviors are attenuated by anxiolytic
drugs. I then modeled these hesitation behaviors as a belief-state updating loop using a partially
observable Markov decision process that involves fictive representations of potential future
outcomes. Next, I explored the neural representations underpinning these anxiety-like
behaviors, aiming to determine whether non-local representations occur during periods of
anxious conflict. To do this, I recorded from ensembles of neurons in dorsal hippocampal layer
CA1 of rats as they freely behaved in the predator-inhabited foraging arena task. I identified
distinct hippocampal fictive representations that co-occurred with two anxiety-like behaviors: (1)
forward sequences during choice-point hesitation that shifted from representing reward in a safe
environment to representing reward and threat in a dangerous environment, and (2) discrete
representations of threat during a change-of-mind behavior. Altogether, these results support the view that anxiety resulting from avoid-approach conflictinvolves representations of hypothetical scenarios and that these fictive representations are, at
least in part, neurally encoded in the hippocampus. These data highlight hippocampal fictive
representations as a potential target for the treatment of anxiety disorders
