Task 1: the impact of HZE particles on other tests in the cognitive domain. Using the flexible battery of tests offered by the touchscreen operant platform, we will identify a behavioral framework for…

This federal contract is a $1,470,094.00 grant awarded by the National Aeronautics and Space Administration (NASA) Shared Services Center to The Children's Hospital of Philadelphia (CHOP) on August 1, 2017. The grant, which does not have a set-aside designation, funds research to determine the impact of high-charge and high-energy (HZE) particles on cognitive and social behaviors in mice, as well as investigate neural network changes underlying HZE-induced improvements in pattern separation. The research aims to understand the effects of space radiation exposure, which is important for astronaut health during long-duration space missions. As a leading pediatric hospital and research center, CHOP has extensive expertise in areas like genetic diseases, pediatric cancer, and mitochondrial disorders, and has been awarded numerous federal contracts and grants to support biomedical research and training aligned with the priorities of agencies such as the National Institutes of Health.

Task 1: the impact of HZE particles on other tests in the cognitive domain. Using the flexible battery of tests offered by the touchscreen operant platform, we will identify a behavioral framework for the HZE particle-induced improvement in pattern separation. We hypothesize HZE particles will improve performance reliant on hippocampal-cortical integrity, but not on striatal-cortical integrity. A) determine the effect of 0 and 3X6.7CGY iron (600 MEV/u) on the performance of male, 6-9 month old (at time of IRR) C57BL6J mice on cognitive battery. If these data reveal significant effects, we will also: i. Determine the effect of 0 and 3X6.7CGY iron (600 MEV/u) on the performance of female, 6-9 month old (at time of IRR) C57BL6J mice on cognitive battery II. Examine an additional group of mice for 0 and 0.1 GY iron (600 MEV/u). B) determine the effect of 0 and 2X0.1CGY silicon (275 MEV/u) on the performance of male, 6-9 month old (at time of IRR) C57BL6J mice on cognitive battery. If these data reveal significant effects, we will also: i. Determine the effect of 0 and 2X0.1CGY silicon (275 MEV/u) on the performance of female, 6-9 month old (at time of IRR) C57BL6J mice on cognitive battery II. Examine an additional group of mice for 0 and 0.1 GY silicon (275 MEV/u). Task 2: the impact of HZE particles on behaviors in the affective/social domain. Pattern separation is important not just to contextual discrimination, but also to the resistance to mood and anxiety disorders. Based on this, and with our previous experience with an ethologically-relevant stressor, social defeat stress (SDS) we will test HZE particle-induced influence in the affective/social domain. We hypothesize that improved pattern separation is linked to resilience to social stressors. A) determine the effect of 0 and 3X6.7CGY iron (600 MEV/u) on the performance of male, 6-9 month old (at time of IRR) C57BL6J mice on the social interaction test (performed after 10 days of SDS). I. If these data reveal significant effects, we will then also examine an additional group of animals for 0 and 0.1 GY iron (600 MEV/u). II. If these data do not reveal significant effects, we will then assess mice post- SDS and social interaction for anxiety and hedonic effects b) determine the effect of 0 and 2X0.1CGY silicon (275 MEV/u) on the performance of male, 6-9 month old (at time of IRR) C57BL6J mice on the social interaction test (performed after 10 days of SDS). I. If these data do not reveal significant effects, we will then assess mice post- SDS and social interaction for anxiety and hedonic effects task 3: indices of neural network perturbation underlying HZE particle exposure- induced improved pattern separation. While improved pattern separation has been causally linked to increased hippocampal neurogenesis [9], our data show HZE particle- induced improvement in pattern separation is actually marked by decreased hippocampal neurogenesis. Using classic (stereology of dentate gyrus interneuron counts) as well as cutting-edge techniques (rnaseq), we will test the hypothesis that HZE particles influence the integrity of hippocampal-cortical neural networks. A) determine the effect of 0 and 3X6.7CGY iron (600 MEV/u) on interneuron neuron number and rnaseq of translating proteins in DG granule neurons in mature NTF3 BAC-trap mice 3 and 6 MON post-irradiation. I. Depending on the results from task 1A, we may then also examine an additional group of animals for 0 and 0.1 GY iron (600 MEV/u), providing sufficient funds remain. B) determine the effect of 0 and 2X0.1CGY silicon (275 MEV/u) on interneuron neuron number and rnaseq of translating proteins in DG granule neurons in mature NTF3 BAC-trap mice 3 and 6 MON post-irradiation. I. Depending on the results from task 1B, we may also determine the effect of 0 and 2X0.1CGY silicon (275 MEV/u).