Crusio_Wim_Slides

							   Equipe Neurogénétique Comportementale
     Behavioral Neurogenetics Laboratory




Responsable: Wim E. Crusio


Centre de Neurosciences Intégratives et Cognitives, CNRS UMR 5228, Bordeaux (Talence), France
Group members



   Yoon H. Cho (MC, Bdx 1)
   Wim E. Crusio (DR, CNRS)
   Philippe Rosay (MC, Bdx 1)
   Jan A. Veenstra (PU, Bdx 1)
Projects and funding

   Habit memory coding by striatal cells in HD transgenic mice
    (Cho; Hereditary Disease Foundation, New York)
   Autistic-like behaviors in Fmr1 knockout mice (Crusio; March of
    Dimes, White Plains, NY)
   Genetic regulation of hippocampal anatomy and learning (Crusio;
    NIMH, Bethesda, MD)
   Identification of amino acid residues of the b-amyloid protein
    involved in the formation of senile plaques in AD (Veenstra;
    Fondation Jerome Lejeune, Paris)
    Autistic-like behaviors in Fmr1 knockout
         mice (Crusio; March of Dimes)


   Wim Crusio (CNRS, PI)
   Maude Bernardet (graduate student; Region Aquitaine)
   Susanna Pietropaolo (postdoc, March of Dimes)
   Philippe Rosay (MC, Bdx 1)
Fmr1 null mutant mice
Model for Fragile X Syndrome




                Face validity√
                Predictive validity
                Construct validity√
Fmr1 null mutant mice
Model for Autism?




   Many Fragile X patients suffer from Autism (or at a
    minimum display autistic features)
   Symptoms in Fragile X Syndrome very variable
   Symptoms in Autism very variable
scan
Left: C57BL/6J wt; Right: C57BL/6J Fmr1 knock-out
Wild-type and mutant on FVB background
Hypothesis

   Fmr1 KO mice will show autistic features
   Mutation effects will vary according to genetic
    background

   Fmr1 KO on C57BL/6J background obtained from
    Neuromice.org (consortium of 3 NIH-funded
    mutagenesis and phenotypic screening facilities)
Planned/currently running experiments

   Behavioral rigidity
   Stereotypical behaviors
   Learning
   Ultrasonic vocalizations
   Neuroanatomy hippocampus and amygdala

   In males from 4 genetic backgrounds: FVB,
    C57BL/6, and reciprocal F1s
Genetic regulation of hippocampal anatomy
and learning (Crusio; NIMH)


   Wim Crusio (CNRS, PI)
   Marie-Paule Algéo (AI, NIMH)
   Brice Bonheur (AI, NIMH)
   Alexis Cornuez (AI, NIMH)
   Philippe Rosay (MC, Bdx 1)
           0
               1
                   2
                       3
                                         4
   NZ
C B
  PB
     -K
   DB
      A
 NM
     RI
    BA
 BA
     LB
C
  57
    BR
C
  57
    BL
  C
      3H
                           Heritability > 50%
Heritability = 32%
                                     12


                                     10
                                                                  rho = -0.92
                                                                  P < 0.001
                                                                  n=9
                  Errors day 5....
                                     8
Errors:
h2 = 0.32                            6
IIPMF:
                                     4
h2 = 0.85

                                     2
rD = -0.88±0.03

                                     0
                                          0   1   2           3          4
                                                      IIPMF
Specific Aims

   Aim 1. Analyze the genetic underpinnings of
    heritable differences in radial-maze learning.
   Aim 2. Analyze the genetic bases of heritable
    differences in hippocampal neurocircuitry.
   Aim 3. Identify Quantitative Trait Loci influencing
    learning ability and hippocampal structure
    simultaneously.

   BXD Recombinant strains obtained from Robert
    Williams (Memphis, TN)
Experiments currently under way

   Radial maze learning
   Neuroanatomy hippocampus

   In males and females from >60 BXD Recombinant
    Inbred Strains (largest collection in Europe)