Premium
Serotonin 5‐ HT 7 receptor increases the density of dendritic spines and facilitates synaptogenesis in forebrain neurons
Author(s) -
Speranza Luisa,
Labus Josephine,
Volpicelli Floriana,
Guseva Daria,
Lacivita Enza,
Leopoldo Marcello,
Bellenchi Gian Carlo,
Porzio Umberto,
Bijata Monika,
PerroneCapano Carla,
Ponimaskin Evgeni
Publication year - 2017
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13962
Subject(s) - dendritic spine , synaptogenesis , neuroscience , forebrain , neurite , synapse , chemistry , biology , microbiology and biotechnology , hippocampal formation , central nervous system , biochemistry , in vitro
Precise control of dendritic spine density and synapse formation is critical for normal and pathological brain functions. Therefore, signaling pathways influencing dendrite outgrowth and remodeling remain a subject of extensive investigations. Here, we report that prolonged activation of the serotonin 5‐ HT 7 receptor (5‐ HT 7R) with selective agonist LP ‐211 promotes formation of dendritic spines and facilitates synaptogenesis in postnatal cortical and striatal neurons. Critical role of 5‐ HT 7R in neuronal morphogenesis was confirmed by analysis of neurons isolated from 5‐ HT 7R‐deficient mice and by pharmacological inactivation of the receptor. Acute activation of 5‐ HT 7R results in pronounced neurite elongation in postnatal striatal and cortical neurons, thus extending previous data on the morphogenic role of 5‐ HT 7R in embryonic and hippocampal neurons. We also observed decreased number of spines in neurons with either genetically (i.e. 5‐ HT 7R‐knock‐out) or pharmacologically (i.e. antagonist treatment) blocked 5‐ HT 7R, suggesting that constitutive 5‐ HT 7R activity is critically involved in the spinogenesis. Moreover, cyclin‐dependent kinase 5 and small GTP ase Cdc42 were identified as important downstream effectors mediating morphogenic effects of 5‐ HT 7R in neurons. Altogether, our data suggest that the 5‐ HT 7R‐mediated structural reorganization during the postnatal development might have a crucial role for the development and plasticity of forebrain areas such as cortex and striatum, and thereby can be implicated in regulation of the higher cognitive functions.Read the Editorial Highlight for this article on page 644.