5-HT₇R/G₁₂Signaling 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 G␣ 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 G␣ 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 G␣ 12 -protein may represent a molecular mechanism by which serotonin specifically modulates formation of initial neuronal networks during early postnatal development.

Serotonin receptor 5-HT7 regulates morphology and migratory properties of dendritic cells

“…In our previous works, we have shown that RhoA can be activated by the 5-HT 7 R, although to a lesser extent than Cdc42 (Kvachnina et al, 2005;Kobe et al, 2012). In contrast to Cdc42, which propels cell movement by promoting cellular extension and spreading, RhoA mediates detachment and cell rounding through regulation of actin filament rearrangements (Graness et al, 2006;Hall, 1994Hall, , 1998Sepp and Auld, 2003;Swetman et al, 2002).…”

“…In this context, members of the Rho family of small GTPases, whose most prominent feature is the regulation of the actin cytoskeleton (Hall, 1994;Machesky and Hall, 1997;Norman et al, 1994) represent key players that are crucially involved in the regulation of dendritic cell migratory properties (Benvenuti et al, 2004;Harada et al, 2012;Lammermann et al, 2009;Ocana-Morgner et al, 2011). Our previous data have indicated that, in neurons, actin cytoskeleton rearrangements can be regulated by 5-HT 7 R through the G 12 protein-mediated activation of the small GTPase Cdc42 (Kobe et al, 2012;Kvachnina et al, 2005;Nobes and Hall, 1995a,b). We have also demonstrated a high basal activity of 5-HT 7 R towards Cdc42 signaling in neuronal cells (Kvachnina et al, 2005), suggesting that both basal activity and agonist-mediated stimulation of the 5-HT 7 R-Cdc42 signaling pathway might contribute to morphological rearrangements of cells.…”

The 5-HT7 receptor triggers cerebellar long-term synaptic depression via PKC-MAPK

“…5-HT7R is considered to play an important role in the maintenance and regulation of balance between potentiation and depression of hippocampal networks (Kobe et al, 2012 andClark andNormann, 2008). In particular, it has been shown that the stimulation of 5-HT7R results in a marked enhancement of spontaneous neuronal activity leading to saturation of LTP and thus preventing further potentiation.…”

Heterodimerization of serotonin receptors 5-HT1A and 5-HT7 differentially regulates receptor signalling and trafficking

“…8B). To study the functional implication of 5-HT 1A -5-HT 7 heterodimerization, we developed short interfering RNAs (siRNAs) to specifically knockdown the endogenously expressed 5-HT 7 receptor (Kobe et al, 2012) (supplementary material Fig. S5A).…”