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Urocortin 3 – Improvement of social memory in knockout mice

The neuropeptide corticotropin-releasing hormone (CRH), as well as its relatives urocortin 1, 2 and 3, are the key factors regulating hormonal and behavioural reaction to stress. Among other things, they act as neuromodulators within the brain and, by binding to CRH receptors, mediate the neuronal communication between different brain regions controlling behaviour. Malfunction of CRH or CRH receptors leads to disturbed stress reactivity and altered anxiety behaviour.

Jan Deussing and his collegues of the Max Planck Institute of Psychiatry have investigated in close collaboration with the Helmholtz Centre Munich which behavioural alterations appear in mice not producing urocortin 3 in the brain (urocortin 3 KO mice). The behavioural testing of urocortin 3 deficient animals in the German Mouse Clinic identified changes in social discrimination abilities. Whereas normal male mice do not recognize a female animal via sense of smell any more already four hours after their first contact, it is only after six hours that urocortin 3 mutant male mice have forgotten the female mouse.

For nocturnal animals like the mouse, the sense of smell is one of the most important information sensors. Discrimination of conspecifics belongs to the central skills of rodents and requires complex data processing in the brain. That urocortin 3 and its specific receptor CRH receptor 2 play a decisive role in this process, was a big surprise to the scientists.

The gene loss accordingly leads to specific improvement of social perception and memory, which is mediated via sense of smell, whereas no general improvement of learning and memory could be detected. Surprisingly, changes could neither be proved in anxiety behaviour nor in regulation of stress hormones. These findings shed new light on the family of CRH-like neuropeptides and their receptors, the functions of which, as has been shown, go far beyond the mediation of stress-associated behaviour.

 

Urocortin 3 Modulates Social Discrimination Abilities via Corticotropin-Releasing Hormone Receptor Type 2“, Deussing et al, Journal of Neuroscience, 30(27):9103-9116. 7. Juli 2010