title: 5-HT7R/G12 signaling regulates neuronal morphology and function in an age-dependent manner.
abstract: 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.
authors.affiliation: DFG-Research Center Molecular Physiology of the Brain (CMPB) and Department of Neuro- and Sensory Physiology, University of Göttingen, 37073 Göttingen, Germany.
authors.forename: Fritz
authors.initials: F
authors.lastname: Kobe
authors.forename: Daria
authors.initials: D
authors.lastname: Guseva
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Jensen
authors.forename: Alexander
authors.initials: A
authors.lastname: Wirth
authors.forename: Ute
authors.initials: U
authors.lastname: Renner
authors.forename: Dietmar
authors.initials: D
authors.lastname: Hess
authors.forename: Michael
authors.initials: M
authors.lastname: Müller
authors.forename: Lucian
authors.initials: L
authors.lastname: Medrihan
authors.forename: Weiqi
authors.initials: W
authors.lastname: Zhang
authors.forename: Mingyue
authors.initials: M
authors.lastname: Zhang
authors.forename: Katharina
authors.initials: K
authors.lastname: Braun
authors.forename: Sören
authors.initials: S
authors.lastname: Westerholz
authors.forename: Andreas
authors.initials: A
authors.lastname: Herzog
authors.forename: Konstantin
authors.initials: K
authors.lastname: Radyushkin
authors.forename: Ahmed
authors.initials: A
authors.lastname: El-Kordi
authors.forename: Hannelore
authors.initials: H
authors.lastname: Ehrenreich
authors.forename: Diethelm W
authors.initials: DW
authors.lastname: Richter
authors.forename: Dmitri A
authors.initials: DA
authors.lastname: Rusakov
authors.forename: Evgeni
authors.initials: E
authors.lastname: Ponimaskin
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D000831:Animals, Newborn; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology* / Q000254:growth & development / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055495:Neurogenesis / Q000235:genetics*; D009474:Neurons / Q000502:physiology*; D009924:Organ Culture Techniques; D011985:Receptors, Serotonin / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics*; D013569:Synapses / Q000235:genetics
chemical_list: D011985:Receptors, Serotonin; C104425:serotonin 7 receptor; D044365:GTP-Binding Protein alpha Subunits, G12-G13