Independent quantitative trait loci influence ventral and dorsal hippocampal volume in recombinant inbred strains of mice

Anatomical and functional studies support segregation of the hippocampus into ventral and dorsal components along its septotemporal axis. However, it is unknown whether the development of these two components of the hippocampus is influenced by common or separate genetic factors. In this study, we used recombinant inbred strains of mice to determine whether the same or different quantitative trait loci (QTL) influence ventral and dorsal hippocampal volume. Using two sets of strains of recombinant inbred mice (BXD and AXB/BXA), we identified separate QTLs for ventral and dorsal hippocampal volume. In BXD mice, suggestive QTLs for ventral hippocampus were identified on chromosomes 2, 8 and 13, and a significant QTL for dorsal hippocampal volume was identified on chromosome 15. There was also a suggestive QTL for dorsal hippocampal volume on chromosome 13. In AXB/BXA mice, there were no significant or suggestive QTLs for ventral hippocampal volume, but a significant QTL for dorsal hippocampus was identified on chromosome 5. These findings suggest that the development of the ventral and dorsal components of the hippocampus is influenced by separate genetic loci.

[1]  J. Rawlins,et al.  Dissociating context and space within the hippocampus: effects of complete, dorsal, and ventral excitotoxic hippocampal lesions on conditioned freezing and spatial learning. , 1999, Behavioral neuroscience.

[2]  Edith V. Sullivan,et al.  Preservation of hippocampal volume throughout adulthood in healthy men and women , 2005, Neurobiology of Aging.

[3]  R. Williams,et al.  Genetic architecture of the mouse hippocampus: identification of gene loci with selective regional effects , 2003, Genes, brain, and behavior.

[4]  D. Treit,et al.  Anxiety is functionally segregated within the septo-hippocampal system , 2004, Brain Research.

[5]  J. Trojanowski,et al.  Human fetal hippocampal development: I. Cytoarchitecture, myeloarchitecture, and neuronal morphologic features , 1996, The Journal of comparative neurology.

[6]  C. Van Petten,et al.  Relationship between hippocampal volume and memory ability in healthy individuals across the lifespan: review and meta-analysis. , 2004, Neuropsychologia.

[7]  J. Feldon,et al.  Dissociation of function between the dorsal and the ventral hippocampus in spatial learning abilities of the rat: a within‐subject, within‐task comparison of reference and working spatial memory , 2004, The European journal of neuroscience.

[8]  Lei Wang,et al.  Hippocampal deformities in the unaffected siblings of schizophrenia subjects , 2003, Biological Psychiatry.

[9]  R. J. Meijer,et al.  Collateral projections from the rat hippocampal formation to the lateral and medial prefrontal cortex , 1997, Hippocampus.

[10]  J. Rawlins,et al.  Ventral hippocampal lesions affect anxiety but not spatial learning , 2003, Behavioural Brain Research.

[11]  Michael D. Nelson,et al.  Hippocampal volume reduction in schizophrenia as assessed by magnetic resonance imaging : A meta-analytic study , 1998 .

[12]  J. Rawlins,et al.  Hippocampal lesions, species-typical behaviours and anxiety in mice , 2005, Behavioural Brain Research.

[13]  D. Arnold,et al.  Mesial temporal damage in temporal lobe epilepsy: a volumetric MRI study of the hippocampus, amygdala and parahippocampal region. , 2003, Brain : a journal of neurology.

[14]  G. Sperk,et al.  Regional heterogeneity in the distribution of neurotransmitter markers in the rat hippocampus , 1991, Neuroscience.

[15]  M. Goldman,et al.  What is the functional significance of hippocampal pathology in schizophrenia? , 2004, Schizophrenia bulletin.

[16]  T. van Groen,et al.  The entorhinal cortex of the mouse: Organization of the projection to the hippocampal formation , 2003, Hippocampus.

[17]  M. van den Buuse,et al.  Functional dissociation between serotonergic pathways in dorsal and ventral hippocampus in psychotomimetic drug‐induced locomotor hyperactivity and prepulse inhibition in rats , 2004, The European journal of neuroscience.

[18]  J. Warter Genes, brain and behavior. , 1991, Research publications - Association for Research in Nervous and Mental Disease.

[19]  Dennis S. Charney,et al.  Reduced hippocampal volume in unmedicated, remitted patients with major depression versus control subjects , 2005, Biological Psychiatry.

[20]  J. Rawlins,et al.  Regional dissociations within the hippocampus—memory and anxiety , 2004, Neuroscience & Biobehavioral Reviews.

[21]  A. Mitsudome,et al.  Development of the temporal lobe in infants and children: analysis by MR-based volumetry. , 1999, AJNR. American journal of neuroradiology.

[22]  F. Benes,et al.  Myelination of a key relay zone in the hippocampal formation occurs in the human brain during childhood, adolescence, and adulthood. , 1994, Archives of general psychiatry.

[23]  H. Grüneberg,et al.  Introduction to quantitative genetics , 1960 .

[24]  M. Trivedi,et al.  Lesions of the ventral hippocampus, but not the dorsal hippocampus, impair conditioned fear expression and inhibitory avoidance on the elevated T-maze , 2004, Neurobiology of Learning and Memory.

[25]  Lu Lu,et al.  The genetic structure of recombinant inbred mice: high-resolution consensus maps for complex trait analysis , 2001, Genome Biology.

[26]  M. Moser,et al.  Functional differentiation in the hippocampus , 1998, Hippocampus.

[27]  R. Greenberg Biometry , 1969, The Yale Journal of Biology and Medicine.

[28]  Richard C Saunders,et al.  Comparison of hippocampal, amygdala, and perirhinal projections to the nucleus accumbens: Combined anterograde and retrograde tracing study in the Macaque brain , 2002, The Journal of comparative neurology.

[29]  D. Amaral,et al.  Topographical organization of the entorhinal projection to the dentate gyrus of the monkey , 1989, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[30]  J. Cheverud,et al.  Quantitative trait loci for obesity- and diabetes-related traits and their dietary responses to high-fat feeding in LGXSM recombinant inbred mouse strains. , 2004, Diabetes.

[31]  A. Ylinen,et al.  Reciprocal Connections between the Amygdala and the Hippocampal Formation, Perirhinal Cortex, and Postrhinal Cortex in Rat: A Review , 2000, Annals of the New York Academy of Sciences.

[32]  Neil Burgess,et al.  Navigation expertise and the human hippocampus: A structural brain imaging analysis , 2003, Hippocampus.

[33]  Hans-Jochen Heinze,et al.  Quantitative MR analyses of the hippocampus: Unspecific metabolic changes in aging , 2004, Journal of Neurology.

[34]  M. Miller,et al.  Hippocampal deformities in schizophrenia characterized by high dimensional brain mapping. , 2002, The American journal of psychiatry.

[35]  G. Rosen,et al.  Quantitative trait loci modulate ventricular size in the mouse brain , 2003, The Journal of comparative neurology.