LSID: http://syli.cz/urn:lsid:public.sylics.com:experiment:4D68-G578-G5A3
| Treatment | Amount | Administration route | Administration time |
Treatment info:
Order of behavioural testing
PhenoTyper Spontaneous Behaviour
PhenoTyper Appetitive Conditioning
PhenoTyper Avoidance Learning
Body Weight
Grip Strength
Novel Home Cage Induced Hypophagia
Elevated Plus Maze
Open Field
Dark/Light Box
Barnes Maze
Fear Conditioning
Published in Biological Psychiatry 2014: http://www.biologicalpsychiatryjournal.com/article/S0006-3223(14)00106-1/abstract
Neuregulin-3 in the Mouse Medial Prefrontal Cortex Regulates Impulsive Action
Maarten Loos (a,b)*, Thomas Mueller (c)*, Yvonne Gouwenberg (a), Ruud Wijnands (a,b), Rolinka J. van der Loo (a,b), Neuro-BSIK Mouse Phenomics consortium (d), Carmen Birchmeier (c), August B. Smit (a)#, Sabine Spijker (a)#
a) Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, Amsterdam, The Netherlands, b) Sylics (Synaptologics BV), Amsterdam, The Netherlands, c) Department of Developmental Biology, Max-Delbrück-Center (MDC) for Molecular Medicine, Berlin, Germany. */# authors with equal first and senior contribution, respectively.
Abstract
Background: A deficit in inhibitory control is a prominent, heritable symptom in several psychiatric disorders, such as addiction, attention-deficit/ hyperactivity disorder (ADHD) and schizophrenia. Here we aimed to identify genes regulating inhibitory control in mice.
Methods: Using the widely used 5-choice serial reaction time task, we measured inhibitory control in 1) a panel of 41 BXD recombinant inbred strains (n = 13.7 ± 0.8 per strain; n=654 total) to detect underlying genetic loci, 2) congenic mice (n=23) to replicate the identified locus, 3) mice overexpressing the Nrg3 candidate gene in the medial prefrontal cortex (n=21) and 4) a Nrg3 loss-of-function mutant (n=59) to functionally implicate the Nrg3 candidate gene in inhibitory control.
Results: Genetic mapping of inhibitory control in the BXD panel identified a locus on chromomose 14 (34.5 - 41.4 Mb), syntenic with the human 10q22-q23 schizophrenia-susceptibility locus. Congenic mice carrying the impulse control locus (imp) confirmed its influence on impulse control. Decreased impulse control was associated with increased Nrg3 gene expression in the medial prefrontal cortex (mPFC). Viral overexpression of Nrg3 in the medial prefrontal cortex (mPFC) decreased impulse control, whereas a constitutive Nrg3 loss-of-function mutation increased impulse control.
Conclusions: The inverse, causal relation between Nrg3 expression in the mPFC and inhibitory control shown here provides a mechanism by which polymorphism in NRG3 in humans contribute to a specific cognitive deficit seen in several psychiatric diseases, such as addiction, attention-deficit/ hyperactivity disorder (ADHD) and schizophrenia.
In this manuscript: Conventional behavioral tests in Nrg3 KO mice
The decrease in impulsive responding in Nrg3-/- mice was not accompanied by a decrease in overall activity; in contrast, Nrg3-/- mice were significantly more active in a novel open field. We observed no differences in tests of anxiety-related behavior, motor function and learning & memory.
Mouse info:
| Mouse ID | Strain | Coat color | Genotype | Ear tag | Internal ID | Sex | Date of Birth | Sub experiment 1 | Sub experiment 2 | Sub experiment 3 |
| PH03849 | Nrg3 | unknown | hom | male | 00-00-0000 | |||||
| PH03850 | Nrg3 | unknown | WT | male | 00-00-0000 | |||||
| PH03851 | Nrg3 | unknown | hom | male | 00-00-0000 | |||||
| PH03852 | Nrg3 | unknown | hetro | male | 00-00-0000 | |||||
| PH03853 | Nrg3 | unknown | hom | male | 00-00-0000 | |||||
| PH03854 | Nrg3 | unknown | hetro | male | 00-00-0000 | |||||
| PH03855 | Nrg3 | unknown | WT | male | 00-00-0000 | |||||
| PH03856 | Nrg3 | unknown | hom | male | 00-00-0000 | |||||
| PH03857 | Nrg3 | unknown | hetro | male | 00-00-0000 | |||||
| PH03858 | Nrg3 | unknown | WT | male | 00-00-0000 | |||||
| PH03859 | Nrg3 | unknown | WT | male | 00-00-0000 | |||||
| PH03860 | Nrg3 | unknown | hetro | male | 00-00-0000 | |||||
| PH03861 | Nrg3 | unknown | WT | male | 00-00-0000 | |||||
| PH03862 | Nrg3 | unknown | hetro | male | 00-00-0000 | |||||
| PH03863 | Nrg3 | unknown | hetro | male | 00-00-0000 | |||||
| PH03864 | Nrg3 | unknown | hetro | male | 00-00-0000 | |||||
| PH03865 | Nrg3 | unknown | hom | male | 00-00-0000 | |||||
| PH03866 | Nrg3 | unknown | hetro | male | 00-00-0000 | |||||
| PH03867 | Nrg3 | unknown | hom | male | 00-00-0000 | |||||
| PH03868 | Nrg3 | unknown | WT | male | 00-00-0000 | |||||
| PH03869 | Nrg3 | unknown | hom | male | 00-00-0000 | |||||
| PH03870 | Nrg3 | unknown | hetro | male | 00-00-0000 | |||||
| PH03871 | Nrg3 | unknown | hetro | male | 00-00-0000 | |||||
| PH03872 | Nrg3 | unknown | hom | male | 00-00-0000 | |||||
| PH03873 | Nrg3 | unknown | WT | male | 00-00-0000 | |||||
| PH03874 | Nrg3 | unknown | hetro | male | 00-00-0000 | |||||
| PH03875 | Nrg3 | unknown | hetro | male | 00-00-0000 | |||||
| PH03876 | Nrg3 | unknown | hom | male | 00-00-0000 | |||||
| PH03877 | Nrg3 | unknown | WT | male | 00-00-0000 | |||||
| PH03878 | Nrg3 | unknown | hetro | male | 00-00-0000 | |||||
| PH03879 | Nrg3 | unknown | hom | male | 00-00-0000 | |||||
| PH03880 | Nrg3 | unknown | hom | male | 00-00-0000 | |||||
| PH03881 | Nrg3 | unknown | WT | male | 00-00-0000 | |||||
| PH03882 | Nrg3 | unknown | WT | male | 00-00-0000 | |||||
| PH03883 | Nrg3 | unknown | WT | male | 00-00-0000 | |||||
| PH03884 | Nrg3 | unknown | WT | male | 00-00-0000 | |||||
| PH03885 | Nrg3 | unknown | WT | male | 00-00-0000 | |||||
| PH03886 | Nrg3 | unknown | hom | male | 00-00-0000 | |||||
| PH03887 | Nrg3 | unknown | hom | male | 00-00-0000 | |||||
| PH03888 | Nrg3 | unknown | hom | male | 00-00-0000 |