TY - JOUR
T1 - Urocortin 3 modulates social discrimination abilities via corticotropin-releasing hormone receptor type 2
AU - Deussing, Jan M.
AU - Breu, Johannes
AU - Kühne, Claudia
AU - Kallnik, Magdalena
AU - Bunck, Mirjam
AU - Glasl, Lisa
AU - Yen, Yi Chun
AU - Schmidt, Mathias V.
AU - Zurmühlen, Regine
AU - Vogl, Annette M.
AU - Gailus-Durner, Valérie
AU - Fuchs, Helmut
AU - Hölter, Sabine M.
AU - Wotjak, Carsten T.
AU - Landgraf, Rainer
AU - De Angelis, Martin Hrabé
AU - Holsboer, Florian
AU - Wurst, Wolfgang
PY - 2010/7/7
Y1 - 2010/7/7
N2 - Urocortin 3 (UCN3) is strongly expressed in specific nuclei of the rodent brain, at sites distinct from those expressing urocortin 1 and urocortin 2, the other endogenous ligands of corticotropin-releasing hormone receptor type 2 (CRH-R2). To determine the physiological role of UCN3, we generated UCN3-deficient mice, in which the UCN3 open reading frame was replaced by a tau-lacZ reporter gene. By means of this reporter gene, the nucleus parabrachialis and the premammillary nucleus were identified as previously unknown sites of UCN3 expression. Additionally, the introduced reporter gene enabled the visualization of axonal projections of UCN3-expressing neurons from the superior paraolivary nucleus to the inferior colliculus and from the posterodorsal part of the medial amygdala to the principal nucleus of the bed nucleus of the stria terminalis, respectively. The examination of tau-lacZ reporter gene activity throughout the brain underscored a predominant expression of UCN3 in nuclei functionally connected to the accessory olfactory system. Male and female mice were comprehensively phenotyped but none of the applied tests provided indications for a role of UCN3 in the context of hypothalamic-pituitary-adrenocortical axis regulation, anxiety-or depression-related behavior. However, inspired by the prevalent expression throughout the accessory olfactory system, we identified alterations in social discrimination abilities of male and female UCN3 knock-out mice that were also present in male CRH-R2 knock-out mice. In conclusion, our results suggest a novel role for UCN3 and CRH-R2 related to the processing of social cues and to the establishment of social memories.
AB - Urocortin 3 (UCN3) is strongly expressed in specific nuclei of the rodent brain, at sites distinct from those expressing urocortin 1 and urocortin 2, the other endogenous ligands of corticotropin-releasing hormone receptor type 2 (CRH-R2). To determine the physiological role of UCN3, we generated UCN3-deficient mice, in which the UCN3 open reading frame was replaced by a tau-lacZ reporter gene. By means of this reporter gene, the nucleus parabrachialis and the premammillary nucleus were identified as previously unknown sites of UCN3 expression. Additionally, the introduced reporter gene enabled the visualization of axonal projections of UCN3-expressing neurons from the superior paraolivary nucleus to the inferior colliculus and from the posterodorsal part of the medial amygdala to the principal nucleus of the bed nucleus of the stria terminalis, respectively. The examination of tau-lacZ reporter gene activity throughout the brain underscored a predominant expression of UCN3 in nuclei functionally connected to the accessory olfactory system. Male and female mice were comprehensively phenotyped but none of the applied tests provided indications for a role of UCN3 in the context of hypothalamic-pituitary-adrenocortical axis regulation, anxiety-or depression-related behavior. However, inspired by the prevalent expression throughout the accessory olfactory system, we identified alterations in social discrimination abilities of male and female UCN3 knock-out mice that were also present in male CRH-R2 knock-out mice. In conclusion, our results suggest a novel role for UCN3 and CRH-R2 related to the processing of social cues and to the establishment of social memories.
UR - http://www.scopus.com/inward/record.url?scp=77954515779&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.1049-10.2010
DO - 10.1523/JNEUROSCI.1049-10.2010
M3 - Article
C2 - 20610744
AN - SCOPUS:77954515779
SN - 0270-6474
VL - 30
SP - 9103
EP - 9116
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 27
ER -