title: Effects of ⁵⁶Fe-particle cranial radiation on hippocampus-dependent cognition depend on the salience of the environmental stimuli.
abstract: 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 ⁵⁶Fe-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.
authors.affiliation: Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, Oregon 97239, USA. raberj@ohsu.edu
authors.forename: Jacob
authors.initials: J
authors.lastname: Raber
authors.forename: Susanna
authors.initials: S
authors.lastname: Rosi
authors.forename: Ayanabha
authors.initials: A
authors.lastname: Chakraborti
authors.forename: Kelly
authors.initials: K
authors.lastname: Fishman
authors.forename: Catherine
authors.initials: C
authors.lastname: Dayger
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Davis
authors.forename: Laura
authors.initials: L
authors.lastname: Villasana
authors.forename: John R
authors.initials: JR
authors.lastname: Fike
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology / Q000528:radiation effects; D003071:Cognition / Q000502:physiology / Q000528:radiation effects*; D003213:Conditioning, Psychological / Q000502:physiology / Q000528:radiation effects; D003598:Cytoskeletal Proteins / Q000378:metabolism; D018891:Dentate Gyrus / Q000166:cytology / Q000378:metabolism / Q000502:physiology / Q000528:radiation effects; D004777:Environment; D005239:Fear / Q000502:physiology / Q000523:psychology / Q000528:radiation effects; D005786:Gene Expression Regulation / Q000528:radiation effects; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism / Q000502:physiology* / Q000528:radiation effects*; D007501:Iron; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000528:radiation effects; D012886:Skull / Q000528:radiation effects*
chemical_list: D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; C092069:activity regulated cytoskeletal-associated protein; D007501:Iron