Effects of 56Fe-Particle Cranial Radiation on Hippocampus-Dependent Cognition Depend on the Salience of the Environmental Stimuli

Raber, J., Rosi, S., Chakraborti, A., Fishman, K., Dayger, C., Davis, M. J., Villasana, L. and Fike, J. R. Effects of Fe-56-Particle Cranial Radiation on Hippocampus-Dependent Cognition Depend on the Salience of the Environmental Stimuli. Radial. Res. 176, 521-526 (2011). Ionizing radiation reduces the numbers of neurons expressing activity-regulated cytoskeleton-associated protein (Arc) in the hippocampal dentate gyrus (DG). It is currently unclear if that change relates to cognitive function. We assessed the effects of 1 Gy of head-only Fe-56-particle irradiation on hippocampus-dependent and hippocampus-independent fear conditioning and determined how those changes related to Arc expression within the DG. Irradiated mice that did not receive tone-shock pairings on day 1 showed less freezing in the same context on a second day and a lower fraction of Arc-expressing neurons in the free (lower) blade of the DG than sham-irradiated mice. Those data suggested reduced hippocampus-dependent spatial habituation learning. Changes in Arc expression in the free blade correlated positively with freezing in mice that did not receive tone-shock pairings. However, irradiated mice that did receive tone-shock pairings showed enhanced contextual freezing but a reduced percentage of Arc-expressing neurons in the enclosed (upper) blade. Changes in Arc expression correlated negatively with freezing in mice that received tone-shock pairings. In animals receiving cued fear conditioning, radiation did not affect cognitive performance or the fractions of Arc-expressing neurons. While the relationship between Arc expression and cognitive performance is complex, our data suggest that radiation effects on hippocampus-dependent cognition might depend on the prominence (salience) of environmental stimuli and blade-specific Arc expression. (C) 2011 by Radiation Research Society