title: Sex and strategy use matters for pattern separation, adult neurogenesis, and immediate early gene expression in the hippocampus.
abstract: Adult neurogenesis in the dentate gyrus (DG) plays a crucial role for pattern separation, and there are sex differences in the regulation of neurogenesis. Although sex differences, favoring males, in spatial navigation have been reported, it is not known whether there are sex differences in pattern separation. The current study was designed to determine whether there are sex differences in the ability for separating similar or distinct patterns, learning strategy choice, adult neurogenesis, and immediate early gene (IEG) expression in the DG in response to pattern separation training. Male and female Sprague-Dawley rats received a single injection of the DNA synthesis marker, bromodeoxyuridine (BrdU), and were tested for the ability of separating spatial patterns in a spatial pattern separation version of delayed nonmatching to place task using the eight-arm radial arm maze. Twenty-seven days following BrdU injection, rats received a probe trial to determine whether they were idiothetic or spatial strategy users. We found that male spatial strategy users outperformed female spatial strategy users only when separating similar, but not distinct, patterns. Furthermore, male spatial strategy users had greater neurogenesis in response to pattern separation training than all other groups. Interestingly, neurogenesis was positively correlated with performance on similar pattern trials during pattern separation in female spatial strategy users but negatively correlated with performance in male idiothetic strategy users. These results suggest that the survival of new neurons may play an important positive role for pattern separation of similar patterns in females. Furthermore, we found sex and strategy differences in IEG expression in the CA1 and CA3 regions in response to pattern separation. These findings emphasize the importance of studying biological sex on hippocampal function and neural plasticity.
authors.affiliation: Graduate Program in Neuroscience, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Shunya
authors.initials: S
authors.lastname: Yagi
authors.affiliation: Department of Psychology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Carmen
authors.initials: C
authors.lastname: Chow
authors.affiliation: Department of Psychology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Stephanie E
authors.initials: SE
authors.lastname: Lieblich
authors.affiliation: Graduate Program in Neuroscience, University of British Columbia, Vancouver, British Columbia, Canada.|Department of Psychology, University of British Columbia, Vancouver, British Columbia, Canada.|Centre for Brain Health, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Liisa A M
authors.initials: LA
authors.lastname: Galea
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D001973:Bromodeoxyuridine; D002452:Cell Count; D002755:Choice Behavior / Q000502:physiology; D051766:Early Growth Response Protein 1 / Q000378:metabolism; D030762:Estrous Cycle / Q000502:physiology; D005260:Female; D017781:Genes, Immediate-Early / Q000502:physiology*; D006624:Hippocampus / Q000033:anatomy & histology / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology; D009483:Neuropsychological Tests; D009929:Organ Size; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D016037:Single-Blind Method; D013037:Spatial Behavior / Q000502:physiology*
chemical_list: D034961:Antigens, Nuclear; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D009419:Nerve Tissue Proteins; D016760:Proto-Oncogene Proteins c-fos; C546339:Rbfox3 protein, rat; D001973:Bromodeoxyuridine
keywords: bromodeoxyuridine; c-Fos; cognition; dentate gyrus; zif268