Anna Delprato, Wim Crusio et al. in Genes Brain Behav

Systems genetic analysis of hippocampal neuroanatomy and spatial learning in mice. Delprato A, Bonheur B, Algéo MP, Rosay P, Lu L, Williams RW, Crusio WE.
Genes Brain Behav. 2015 Oct 9. doi: 10.1111/gbb.12259

Wim Crusio /Team leader: Behavioral Neurogenetics and Co-director of the Cognitive and Integrative Neuroscience – Aquitaine Institute

Wim Crusio: This study was the culmination of a project started in 2006, about a year after my arrival in Bordeaux. Ambitious and both time and resource intensive, it involved about 6 years of testing nearly 1000 male and female mice from 53 Recombinant Inbred Strains derived from C57BL/6J  and DBA/2J. The subsequent analysis of the mass of data then took another couple of years to complete. The primary goal of this study was to identify chromosomal regions, and possibly even genes, involved in differences in hippocampal neuroanatomy and performance in a spatial navigation learning task in a radial maze. Research carried out over several decades by my collaborators and me ( Crusio and Schwegler, 2005, for a review) had shown that the extent of the hippocampal intra- and infrapyramidal mossy fiber (IIPMF) terminal fields is strongly correlated with performance in such tasks, with animals having larger projections generally performing better.

The 53 Recombinant Inbred Strains showed, as expected, large differences for the different neuroanatomical and behavioral characters studied and we used a quantitative genetics approach to detect Quantitative Trait Loci (QTLs: narrow chromosomal intervals) underlying the genetic basis for this variation. A number of significant QTL were detected for several neuroanatomical traits, as well as for spatial learning performance. The IIPMF data rendered the clearest results. We detected two QTL, one on the X chromosome and one on chromosome 11. Closer inspection narrowed these regions down to two genes, Gpc4 and Tenm2, respectively, both of which encode glycoproteins that interact with cell surface and extracellular matrix proteins. Future research will have to elucidate the exact ways in which these genes influence size variations in hippocampal neuroanatomy. (below: zoomable picts)

Whole genome scans for for IIPMF sizes

Timm-stained mouse hippocampus, counterstained with methylene blue. Mossy fibers are stained in dark brown.

Schematiques representation of the hippocampus showing the localization of the intra- and infrapyramidal mossy fibers (IIPMF)

 Publications Crusio WE