5-HT 7 R/G 12 Signaling Regulates Neuronal Morphology and Function in an Age-Dependent Manner

• Published in: The Journal of neuroscience 2012-02, Vol.32 (9), p.2915-2930
• Main Authors: Kobe, Fritz, Guseva, Daria, Jensen, Thomas P., Wirth, Alexander, Renner, Ute, Hess, Dietmar, Müller, Michael, Medrihan, Lucian, Zhang, Weiqi, Zhang, Mingyue, Braun, Katharina, Westerholz, Sören, Herzog, Andreas, Radyushkin, Konstantin, El-Kordi, Ahmed, Ehrenreich, Hannelore, Richter, Diethelm W., Rusakov, Dmitri A., Ponimaskin, Evgeni
• Format: Article
• Language: English
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/JNEUROSCI.2765-11.2012

The common neurotransmitter serotonin controls different aspects of early neuronal differentiation, although the underlying mechanisms are poorly understood. Here we report that activation of the serotonin 5-HT 7 receptor promotes synaptogenesis and enhances synaptic activity in hippocampal neurons at early postnatal stages. An analysis of Gα 12 -deficient mice reveals a critical role of G 12 -protein for 5-HT 7 receptor-mediated effects in neurons. In organotypic preparations from the hippocampus of juvenile mice, stimulation of 5-HT 7 R/G 12 signaling potentiates formation of dendritic spines, increases neuronal excitability, and modulates synaptic plasticity. In contrast, in older neuronal preparations, morphogenetic and synaptogenic effects of 5-HT 7 /G 12 signaling are abolished. Moreover, inhibition of 5-HT 7 receptor had no effect on synaptic plasticity in hippocampus of adult animals. Expression analysis reveals that the production of 5-HT 7 and Gα 12 -proteins in the hippocampus undergoes strong regulation with a pronounced transient increase during early postnatal stages. Thus, regulated expression of 5-HT 7 receptor and Gα 12 -protein may represent a molecular mechanism by which serotonin specifically modulates formation of initial neuronal networks during early postnatal development.