Sex- and dose-dependent effects of calcium ion irradiation on behavioral performance of B6D2F1 mice during contextual fear conditioning training

The space radiation environment includes energetic charged particles that may impact behavioral and cognitive performance. The relationship between the dose and the ionization density of the various types of charged particles (expressed as linear energy transfer or LET), and cognitive performance is complex. In our earlier work, whole body exposure to ²⁸Si ions (263 MeV/n, LET=78keV/μm; 1.6 Gy) affected contextual fear memory in C57BL/6J × DBA2/J F1 (B6D2F1) mice three months following irradiation but this was not the case following exposure to ⁴⁸Ti ions (1 GeV/n, LET=107keV/μm; 0.2 or 0.4 Gy). As an increased understanding of the impact of charged particle exposures is critical for assessment of risk to the CNS of astronauts during and following missions, in this study we used ⁴⁰Ca ion beams (942 MeV/n, LET=90keV/μm) to determine the behavioral and cognitive effects for the LET region between that of Si ions and Ti ions. ⁴⁰Ca ion exposure reduced baseline activity in a novel environment in a dose-dependent manner, which suggests reduced motivation to explore and/or a diminished level of curiosity in a novel environment. In addition, exposure to ⁴⁰Ca ions had sex-dependent effects on response to shock. ⁴⁰Ca ion irradiation reduced the response to shock in female, but not male, mice. In contrast, ⁴⁰Ca ion irradiation did not affect fear learning, memory, or extinction of fear memory for either gender at the doses employed in this study. Thus ⁴⁰Ca ion irradiation affected behavioral, but not cognitive, performance. The effects of ⁴⁰Ca ion irradiation on behavioral performance are relevant, as a combination of novelty and aversive environmental stimuli is pertinent to conditions experienced by astronauts during and following space missions.