FUTURE MISSIONS IN SPACE (SUCH AS A MISSION TO MARS OR THE ESTABLISHMENT OF A MOON BASE) WILL INVOLVE LONG-TERM TRAVEL BEYOND THE MAGNETIC FIELD OF THE EARTH SUBJECTING ASTRONAUTS TO RADIATION HAZARDS POSED BY SOLAR FLARES AND GALACTIC COSMIC RAYS. COSMIC RAYS ARE COMPOSED OF PROTONS ALPHA PARTICLES AND PARTICLES OF HIGH ENERGY AND CHARGE (HZE PARTICLES). PREVIOUS RESEARCH HAS SHOWN THAT EXPOSURE TO SINGLE ABOVE THRESHOLD DOSES OF HZE PARTICLES AND PROTONS CAN AFFECT NEURAL FUNCTIONING AND BEHAVIOR. THESE CHANGES MAY AFFECT THE ABILITY OF ASTRONAUTS TO SUCCESSFULLY MEET MISSION REQUIREMENTS OR MAY PRODUCE DEGENERATIVE CHANGES IN NEURONAL AND BEHAVIORAL FUNCTIONING AFTER THE CONCLUSION OF THE MISSION. THE EFFECTS OF EXPOSURE TO MULTIPLE SUBTHRESHOLD DOSES OF THE SAME ORDIFFERENT PARTICLES OR PROTONS HAVE NOT BEEN EXTENSIVELY STUDIED. THE OBJECTIVES OF THE PROPOSED RESEARCH PROGRAM ARE: (1) TO EVALUATE THE EFFECTS OF REPEATED SUBTHRESHOLD EXPOSURES TO THE SAME AND DIFFERENT HZE PARTICLES AND PROTONS ON COGNITIVE AND NEURONAL DEFICITS AND HOW THEY RELATE TO THE CHARACTERISTICS OF THE SPECIFIC PARTICLE; (2) TO DETERMINE THE RELATIONSHIP BETWEEN CHANGES IN PERFORMANCEAND HZE PARTICLE- AND PROTON-INDUCED CHANGES IN OXIDATIVE STRESS INFLAMMATION SIGNALING MOLECULES AND AUTOPHAGY IN KEY BRAIN REGIONS; AND (3) TO DETERMINE HOW INDIVIDUAL CHARACTERISTICS INCLUDING AGE AND SEX MAY INFLUENCE THE RESPONSIVENESS OF THE INDIVIDUAL TO HZE PARTICLE IRRADIATION.