title: Examining the sex- and circadian dependency of a learning phenotype in mice with glycine transporter 1 deletion in two Pavlovian conditioning paradigms.
abstract: Behavioural characterisation of transgenic mice has been instrumental in search of therapeutic targets for the modulation of cognitive function. However, little effort has been devoted to phenotypic characterisation across environmental conditions and genomic differences such as sex and strain, which is essential to translational research. The present study is an effort in this direction. It scrutinised the stability and robustness of the phenotype of enhanced Pavlovian conditioning reported in mice with forebrain neuronal deletion of glycine transporter 1 by evaluating the possible presence of sex and circadian dependency, and its consistency across aversive and appetitive conditioning paradigms. The Pavlovian phenotype was essentially unaffected by the time of testing between the two circadian phases, but it was modified by sex in both conditioning paradigms. We observed that the effect size of the phenotype was strongest in female mice tested during the dark phase in the aversive paradigm. Critically, the presence of the phenotype in female mutants was accompanied by an increase in resistance to extinction. Similarly, enhanced conditioned responding once again emerged solely in female mutants in the appetitive conditioning experiment, which was again associated with an increased resistance to extinction across days, but male mutants exhibited an opposite trend towards facilitation of extinction. The present study has thus added hitherto unknown qualifications and specifications of a previously reported memory enhancing phenotype in this mouse line by identifying the determinants of the magnitude and direction of the expressed phenotype. This in-depth comparative approach is of value to the interpretation of behavioural findings in general.
authors: Laboratory of Behavioural Neurobiology, Swiss Federal Institute of Technology Zürich, Schörenstrasse 16, 8603 Schwerzenbach, Switzerland.
authors: Sylvain
authors: S
authors: Dubroqua
authors: Detlev
authors: D
authors: Boison
authors: Joram
authors: J
authors: Feldon
authors: Hanns
authors: H
authors: Möhler
authors: Benjamin K
authors: BK
authors: Yee
references: J Neurosci Methods. 1998 Dec 31;86(1):91-9
references: 9894789
references: J Neurosci. 1989 Sep;9(9):3040-57
references: 2552039
references: Physiol Behav. 2006 May 30;87(5):870-80
references: 16600314
references: Behav Neurosci. 2009 Oct;123(5):1012-27
references: 19824767
references: Psychol Bull. 1990 Nov;108(3):442-61
references: 1980149
references: J Exp Psychol. 1953 Aug;46(2):107-12
references: 13084854
references: Annu Rev Neurosci. 2000;23:649-711
references: 10845078
references: Neuropharmacology. 2000 Oct;39(13):2779-84
references: 11044747
references: Learn Mem. 2005 May-Jun;12(3):327-33
references: 15897254
references: Lab Anim. 2006 Oct;40(4):371-81
references: 17018208
references: Nat Rev Neurosci. 2010 Jan;11(1):9-17
references: 20019686
references: Psychopharmacology (Berl). 2009 Jan;202(1-3):385-96
references: 18709358
references: Behav Neurosci. 2007 Oct;121(5):815-25
references: 17907814
references: Psychol Bull. 1993 Jul;114(1):80-99
references: 8346330
references: Physiol Behav. 2009 May 25;97(2):229-38
references: 19272397
references: Neuropsychopharmacology. 2005 Nov;30(11):1963-85
references: 15956994
references: Learn Mem. 2006 Mar-Apr;13(2):192-200
references: 16547163
references: Genes Brain Behav. 2004 Jun;3(3):167-77
references: 15140012
references: Neuroscience. 2009 Dec 15;164(3):887-95
references: 19761818
references: Behav Neurosci. 2010 Dec;124(6):839-50
references: 21038935
references: Behav Brain Res. 2010 Nov 12;213(1):19-26
references: 20412818
references: Learn Mem. 2004 Sep-Oct;11(5):501-9
references: 15466300
references: Nature. 2010 Jun 10;465(7299):690
references: 20535186
references: J Neurosci. 2006 Mar 22;26(12):3169-81
references: 16554468
references: Chronobiol Int. 1994 Jun;11(3):146-55
references: 8082223
references: Nature. 1986 Feb 27-Mar 5;319(6056):774-6
references: 2869411
references: Eur J Neurosci. 2004 Oct;20(7):1928-36
references: 15380015
references: Ann N Y Acad Sci. 1996 Jun 15;786:348-61
references: 8687034