Behavioural Neuroscience
The Behavioural Neuroscience Team investigates the molecular and genetic basis of emotional and cognitive dysfunctions that are relevant for human neuropsychiatric disorders. Neuropsychiatric disorders are associated with quantitative phenotypes called “intermediate traits” or “endophenotypes”, some of which, in contrast to the full complex disorder, can readily be modeled in mice. These traits are risk factors which are considered to be closer to the genetic etiology than the full syndrome. Examples are anxiety in depression, prepulse inhibition and working memory deficits in schizophrenia, and social interaction deficits in autism and schizophrenia (Seong et al., 2002; Gottesman & Gould, 2003; Inoue & Lupski, 2003). We are particularly interested in emotional, social and cognitive endophenotypes that are relevant for anxiety disorders, post-traumatic stress disorder, depression, schizophrenia, autism, attention-deficit hyperactivity disorder, Parkinson’s and Alzheimer’s Disease.
Phenotypes are influenced by genetic predisposition, developmental processes and environmental factors. Therefore we investigate the effects of these influences, and of their interaction, on behaviour and on neuronal function. To this end we subject genetic mouse models to different challenges and environmental conditions, and subsequently apply behavioural, pharmacological and histological analysis techniques. With this approach we generate new, or test known hypotheses of disease mechanisms in relevant mouse models, with the aim to indicate new avenues for therapeutic interventions and drug development.
Within the National Genome Research Network (NGFN), we run the Behavioural Screen of the German Mouse Clinic, and engaged in the development of new analysis tools and in the standardisation of behavioural testing procedures across mouse phenotyping centres in the EU-Projects EUMORPHIA (FP5) and EUMODIC (FP6). We are also partners in the Helmholtz Alliance for Mental Health in an Ageing Society (HelMA).
Most important publications:
Hölter SM, Cryan JF. Phenotyping of Behavioural Characteristics. In: Encyclopedia of Psychopharmacology, Ian P. Stolerman (ed.), Springer-Verlag (2010); DOI 10.1007/978-3-540-68706-1
Deussing JM, Breu J, Kühne C, Kallnik M, Bunck M, Glasl L, Yen YC, Vogl AM, Gailus-Durner V, Fuchs H, Hölter SM, Wotjak CT, Landgraf R, Hrabe de Angelis M, Holsboer F, Wurst W. (2010) Urocortin 3 modulates social discrimination abilities via corticotrophin-releasing hormone receptor 2. J Neurosci 30(27):9103-9116
Shimokawa N, Haglund K, Hölter SM, Grabbe C, Kirkin V, Koibuchi N, Schulz C, Rozman J, Hoeller D, Qiu CH, Londono MB, Jedlicka P, Schwarzacher SW, Wolfer DP, Ehrhardt N, Heuchel R, Nezis I, Brech A, Schmidt MHH, Fuchs H, Gailus-Durner V, Klingenspor M, Bogler O, Wurst W, Deller T, Hrabé de Angelis M, Dikic I. (2010) CIN85 regulates dopamine receptor endocytosis and governs behaviour in mice. EMBO J 29(14):2421-2432
Enard W, Gehre S, Hammerschmidt K, Hölter SM, Brückner MK, Schreiweis C, Winter C, Sohr R, Becker L, Wiebe V, Nickel B, Müller U, Groszer M, Adler T, Bolle I, Calzada-Wack J, Dalke C, Ehrhardt N, Favor J, Fuchs H, Gailus-Durner V, Hans W, Hölzlwimmer G, Javaheri A, Kallnik M, Kling E, Kunder S, Moßbrugger I, Racz I, Rathkolb B, Rozman J, Schrewe A, Busch DH, Graw J, Ivandic B, Kalaydjiev S, Klingenspor M, Klopstock T, Ollert M, Quintanilla-Martinez L, Schulz H, Wolf E, Wurst W, Zimmer A, Fisher SE, Morgenstern R, Ahrendt T, Hrabe de Angelis M, Fischer J, Schwarz J, Pääbo S. (2009) A humanized version of Foxp2 affects cortico-basal ganglia circuits in mice. Cell 137(5):961-71
Mandillo S*, Tucci V*, Hölter SM*, Nolan PM*, Meziane H*, Ouagazzal A*, Kallnik M*, Al Banchaabouchi M*, Coghill EL, Gale K, Golini E, Jacquot S, Krezel W, Lad H, Parker A, Riet F, Schneider I, Marazziti D, Auwerx J, Brown SDM, Chambon P, Rosenthal N, Tocchini-Valentini G, Wurst W. (2008) Reliability, Robustness and Reproducibility in mouse behavioral phenotyping: a cross-laboratory study. Physiol Genomics 34(3):243-255
*authors contributed equally