Astronauts on interplanetary space missions -such as to Mars -will be exposed to space radiation, a spectrum of highly-charged, fast-moving particles that includes 56 Fe and 28 Si. Earth-based preclinical studies with mature, "astronaut-aged" rodents show space radiation decreases performance in lowand some high-level cognitive tasks. Given the prevalence of touchscreens in astronaut training and in-mission assessment, and the ability of rodent touchscreen tasks to assess the functional integrity of brain circuits and multiple cognitive domains in a non-aversive way, it is surprising the effect of space radiation on rodent touchscreen performance is unknown. To fill this knowledge gap, 6-month-old C57BL/6J male mice were exposed to whole-body space radiation and assessed on a touchscreen battery starting 1-month later. Relative to Sham, 56 Fe irradiation did not overtly change performance on tasks of visual discrimination, reversal learning, rule-based, or object-spatial paired associates learning, suggesting preserved functional integrity of supporting brain circuits.Surprisingly, 56 Fe irradiation led to better performance on a dentate gyrus-reliant task of pattern separation ability. Irradiated mice discriminated similar visual cues in ~40% fewer days and ~40% more accurately than control mice. Improved pattern separation was not touchscreen-, radiation-particle, or neurogenesis-dependent, as both 56 Fe and 28 Si irradiation led to faster context discrimination (e.g. Sham Block 5 vs. 56 Fe Block 2) in a non-touchscreen task and 56 Fe led to fewer new dentate gyrus neurons relative to Sham. These data urge revisitation of the broadly-held view that space radiation is detrimental to cognition.
SIGNIFICANCE STATEMENTAstronauts on an interplanetary mission -such as to Mars -will be unavoidably exposed to galactic cosmic radiation, a spectrum of highly-charged, fast-moving particles. Rodent studies suggest space radiation is detrimental to cognition. However, here we show this is not universally true. Mature mice that received whole body exposure to Mars-relevant space radiation perform similarly to control mice on high-level cognitive tasks, reflecting the functional integrity of key neural circuits. Even more surprisingly, irradiated mice perform better than controls in both appetitive and aversive tests of pattern separation, a mission-critical task reliant on dentate gyrus integrity. Notably, improved pattern separation was not touchscreen-, radiation-particle-, or neurogenesis-dependent. Our work urges revisitation of the generally-accepted conclusion that space radiation is detrimental to cognition.3 RESULTS Mice exposed to whole body 56 Fe radiation demonstrate overall normal perceptual discrimination, association learning, and cognitive flexibility in touchscreen testing.Whole body 56 Fe IRR was delivered via fractionation (Frac; 3 exposures of 6.7 cGy every other day, total 20 cGy) to male C57BL/6J mice at 6 mon of age. This total dose is submaximal to that predicted for a Mars mission (9, 66) , and the fr...