Investigating the Contributions of Hippocampal Memory and Reward Valuation Systems to Cost-Benefit Decision Making

Abstract

The hippocampus has for many decades been thought of as an essential brain region for learning about new events, often described in terms of the contexts within which particular associations, actions and outcomes occur. However, little is understood about how hippocampal context analyses impact downstream decision processes. Comparison of current events to past experiences influences our evaluation of salient stimuli, allows memory to serve a prospective organizational function, and the use of past experiences to guide current decision making processes is essential for optimal decision making. However, we know that it is rare to observe phasic neural responses to rewards, or to cues that predict rewards, by hippocampal cells in the same way that we would observe in other neurons, such as ventral tegmental area (VTA) dopamine neurons. Therefore, we sought to understand how reward and value information was represented at the level of hippocampal processing during complex decision making. To do this, we recorded hippocampal neural activity while rats performed a complex decision-making task: a maze based probability discounting task. We assessed whether the hippocampal neurons would differentiate the context based on dynamic reward contingencies. In addition, we compared timing of these changing neural representations to VTA dopamine neural processing on the same task as they are functionally and anatomically connected to the hippocampus. It is important to understand how brain regions in decision-relevant circuits process goal relevant stimuli differentially that can feed into memory representations of what is and isn’t salient. Our first region of interest was the periaqueductal gray (PAG) as it has previously been demonstrated that it is anatomically connected to the VTA. This connection may provide a modulatory effect over the functional loop of the VTA-hippocampus by which behavior, learning, and memory mediated by the VTA are influenced by information processed in the PAG. However, it has not previously been demonstrated that the PAG encodes rewarding stimuli. Therefore, another one of the aims of this dissertation is to ascertain whether PAG neurons encode appetitive stimuli. To do this, we recorded the in-vivo activity of PAG neurons while rats performed a differential-reward working memory task. Lastly, another goal of the current dissertation was to try to assess how these decision-making and memory functions may be affected with age. It is thought that age-related decline in separate neural systems occurs independently from each other. However, because the hippocampus is so intricately linked within a circuit that processes rewards and is essential to differentiating contexts, a functional decline in the hippocampus over time may impact decision making. Therefore, we examined the relationship between declines in spatial working memory performance and changes in risky decision making in aged rats and young controls. Additionally, we wanted to assess if observed changes in risk-based decision making behavior was linked to a functional decline in VTA neural processes on rewards and reward-relevant stimuli.