Urocortin 3 modulates social discrimination abilities via corticotropin-releasing hormone receptor type 2.
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.
Deussing
Jan M
JM
Max-Planck-Institut für Psychiatrie, Munich, Germany. deussing@mpipsykl.mpg.de
Breu
Johannes
J
Kühne
Claudia
C
Kallnik
Magdalena
M
Bunck
Mirjam
M
Glasl
Lisa
L
Yen
Yi-Chun
YC
Schmidt
Mathias V
MV
Zurmühlen
Regine
R
Vogl
Annette M
AM
Gailus-Durner
Valérie
V
Fuchs
Helmut
H
Hölter
Sabine M
SM
Wotjak
Carsten T
CT
Landgraf
Rainer
R
de Angelis
Martin Hrabé
MH
Holsboer
Florian
F
Wurst
Wolfgang
W
D000161:Acoustic Stimulation / Q000379:methods; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002940:Circadian Rhythm / Q000502:physiology; D003345:Corticosterone / Q000097:blood; D004192:Discrimination, Psychological / Q000502:physiology*; D005239:Fear / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D007266:Inhibition, Psychological; D007398:Interpersonal Relations; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism; D009812:Odorants; D009833:Olfactory Pathways / Q000502:physiology; D010465:Perception / Q000502:physiology; D010913:Pituitary-Adrenal System / Q000196:embryology; D011863:Radioimmunoassay / Q000379:methods; D018019:Receptors, Corticotropin-Releasing Hormone / Q000172:deficiency / Q000378:metabolism*; D021641:Recognition, Psychology / Q000502:physiology*; D013216:Reflex, Startle / Q000235:genetics; D018709:Statistics, Nonparametric; D013550:Swimming / Q000502:physiology; D054832:Urocortins / Q000172:deficiency / Q000378:metabolism*
C101531:CRF receptor type 2; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; D003345:Corticosterone