Impacts of the Medial Prefrontal Cortex and Hippocampus in Decision-Making

Abstract

The Hippocampus (HPC) and medial Prefrontal Cortex (mPFC) are known to be two of the most vital structures underlying decision-making and spatial working memory (SWM) abilities across species. Known for its role in episodic and spatial memory, current models suggest the HPC integrates current sensory information with recent experiences to build flexible representations of local environments. During decision-making HPC dynamically recruits the mPFC to gain access to specific task-relevant features, such as rules and strategies, to aid in deliberation. Furthermore, while activity and communication between both structures is shown to increase around the same timepoint that decisions are made, there exists evidence of neural activity in both structures that is related with task events which occur outside of this “choice” time window. This activity may represent the encoding, maintenance, and retrieval of task-relevant information (i.e., reward outcome) in working-memory. To test these hypotheses, past studies generally relied on lesions or pharmacologic manipulations of brain areas. While these methods have provided an abundance of meaningful work, their downfall is that they last for the entirety of testing sessions. Therefore, these methods lack the ability to manipulate neural activity on the discrete time scales necessary to casually probe these more fine-grained observations related to specific mnemonic functions of the mPFC, specifically in its involvement in distinct SWM task phases, which we believe engage distinct mnemonic processes. Thus, a major focus of the present research was to use optogenetic manipulations, capable of transiently disrupting neural activity on discrete timescales, to probe into specific contributions made by the mPFC during SWM decision-making. The second focus of this research was to investigate the neural dynamics of a potential decision-making network involving dorsal and ventral HPC subdivisions and their interactions with the mPFC. Chapter 1 reviews relevant literature on HPC and mPFC while highlighting evidence of their functional interactions during decision-making and SWM. Chapter 2 presents data from a study which utilizes optogenetic epoch-specific manipulations to reveal the mPFC is only needed during deliberation and choice selection of a commonly used SWM task. Chapter 3 also utilizes optogenetic manipulations to probe into the mPFCs role in specific functions of WM during flexible memory-guided decision-making. Chapter 4 investigates contributions of the mPFC, dorsal HPC, and ventral HPC by analyzing neural oscillations in this circuit during a SWM task, importantly revealing a novel interpretation of the results in chapters 2 and 3. Finally, chapter 5 discusses the collective contributions of these studies, which aid our understanding of the impacts of the mPFC and HPC in memory-guided decision-making.