Genetic influences on hippocampal structure and function in recombinant inbred mice

• Published in: Behavioural brain research Vol. 196; no. 1; pp. 78 - 83
• Main Authors: Martin, Maureen V., Churchill, James D., Dong, Hongxin, Wozniak, David F., Cheverud, James M., Csernansky, John G.
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 03.01.2009; Elsevier
• Subjects: Age Factors; Analysis of Variance; Animals; Anxiety - psychology; Behavioral psychophysiology; Biological and medical sciences; Exploratory Behavior - physiology; Fundamental and applied biological sciences. Psychology; Genotype; Hippocampus; Hippocampus - anatomy & histology; Hippocampus - physiology; Maze Learning - physiology; Memory, Short-Term - physiology; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Mice, Inbred Strains; Motor Activity - physiology; Polymerase Chain Reaction; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; QTL; Quantitative Trait Loci - genetics; Reactive Inhibition; Recombinant inbred mice; Recombination, Genetic; Reflex, Startle - physiology; Sensory Gating; Spatial Behavior - physiology; Species Specificity; Structure/function relationships; QTL; Structure/function relationships; Recombinant inbred mice; Hippocampus; Rodentia; Central nervous system; Genetic determinism; Structure function relationship; Encephalon; Vertebrata; Mammalia; Mouse; Animal; Structure
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2008.07.029

Previously, we identified separate genetic influences on ventral versus dorsal hippocampal volume in BXD recombinant inbred mice [Martin MV, Dong HX, Vallera D, Lu L, Williams RW, Rosen GD, et al. Independent quantitative trait loci influence ventral and dorsal hippocampal volume in recombinant inbred strains of mice. Genes Brain Behav 2006;5:614–23]. Based on genotype at genetic markers associated with ventral hippocampal volume, we evaluated BXD mouse strains with relatively small versus large ventral hippocampal volumes using numerous behavioral paradigms known to rely upon hippocampal function and several other tasks that tap into behaviors analogous to those often impaired in schizophrenia. We observed a relationship between genotype at markers known to influence ventral hippocampal volume and working memory at an intermediate memory load. There was no association between genotype at markers known to influence ventral hippocampal volume and spatial reference memory, prepulse inhibition, or elevated plus maze performance. The relevance of these findings for understanding the pathophysiology of schizophrenia are discussed, including the possibility that genetic predisposition toward anterior hippocampal volume reductions and working memory deficits in schizophrenia may be related through a shared genetic locus.