Simulated Space Radiation: Effects on Murine Behavior and Neurogenesis
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An unavoidable consequence of deep space exploration is exposure to high-atomic number, high-energy (HZE) particles, such as 28Si or 56Fe, that comprise galactic cosmic radiation (GCR). It is widely believed that GCR is damaging to the brain, as HZE particle exposure decreases rodent hippocampal dentate gyrus neurogenesis as well as function (e.g. learning and memory). While this raises concern that GCR will compromise astronaut health and mission success, most data have been collected using a specific set of parameters: 2 month old mice or rats (age-equivalent to a teenage human) irradiated with 56Fe. For this dissertation, I have filled three major knowledge gaps with regards to space radiation, brain, and behavior, which are described in the five chapters of my dissertation. In my introductory chapter, Chapter 1, I provide the essential background needed to understand the research chapters, including an overview of the hippocampus, the process of neurogenesis and how radiation affects it, and in-depth look at the published literature on how space radiation influences the central nervous system (CNS). In Chapter 2, I present my published work (Whoolery et al. 2017) on how dentate gyrus neurogenesis is changed at two timepoints post-28Si irradiation (24 h and 3 months), and explain how 28Si-induced changes in dentate gyrus neurogenesis compares to the effects seen after exposure to other previously-studied ions. In Chapter 3, I present my submitted work on how dentate gyrus-dependent behaviors are changed after 6 month old mice are exposed to mission-relevant doses of 56Fe. I test mice on many behavioral paradigms, but the most striking results come from two pattern separation tasks: the aversive Contextual Discrimination Fear Conditioning (CDFC) task and the appetitive Location Discrimination (LD) task which is performed on the Lafayette Bussey touchscreen platform. As I show in Chapter 3, mice exposed to 56Fe radiation display surprisingly improved performance on both CDFC and LD, findings which are discussed in relation to mission-critical behaviors and prior results on space radiation-induced changes in behavior. In Chapter 4, I expand on the operant touchscreen data provided. Specifically, I investigate whether the 56Fe-induced improvement in pattern separation is transient and if it is sex-specific. In my conclusion chapter, Chapter 5, I summarize the main conclusions of Chapters 2-4, provided future directions for each project, possible mechanisms that may underlie this improvement in pattern separation, and end with my thoughts on remaining challenges in the field and obstacles that need to be overcome.