Description:
<jats:title>Abstract</jats:title><jats:sec><jats:label /><jats:p>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‐<jats:styled-content style="fixed-case">HT</jats:styled-content>7 receptor (5‐<jats:styled-content style="fixed-case">HT</jats:styled-content>7R) with selective agonist <jats:styled-content style="fixed-case">LP</jats:styled-content>‐211 promotes formation of dendritic spines and facilitates synaptogenesis in postnatal cortical and striatal neurons. Critical role of 5‐<jats:styled-content style="fixed-case">HT</jats:styled-content>7R in neuronal morphogenesis was confirmed by analysis of neurons isolated from 5‐<jats:styled-content style="fixed-case">HT</jats:styled-content>7R‐deficient mice and by pharmacological inactivation of the receptor. Acute activation of 5‐<jats:styled-content style="fixed-case">HT</jats:styled-content>7R results in pronounced neurite elongation in postnatal striatal and cortical neurons, thus extending previous data on the morphogenic role of 5‐<jats:styled-content style="fixed-case">HT</jats:styled-content>7R in embryonic and hippocampal neurons. We also observed decreased number of spines in neurons with either genetically (i.e. 5‐<jats:styled-content style="fixed-case">HT</jats:styled-content>7R‐knock‐out) or pharmacologically (i.e. antagonist treatment) blocked 5‐<jats:styled-content style="fixed-case">HT</jats:styled-content>7R, suggesting that constitutive 5‐<jats:styled-content style="fixed-case">HT</jats:styled-content>7R activity is critically involved in the spinogenesis. Moreover, cyclin‐dependent kinase 5 and small <jats:styled-content style="fixed-case">GTP</jats:styled-content>ase Cdc42 were identified as important downstream effectors mediating morphogenic effects of 5‐<jats:styled-content style="fixed-case">HT</jats:styled-content>7R in neurons. Altogether, our data suggest that the 5‐<jats:styled-content style="fixed-case">HT</jats:styled-content>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.</jats:p></jats:sec><jats:sec><jats:label /><jats:p>
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</jats:p><jats:p>Read the Editorial Highlight for this article on <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="https://doi.org/10.1111/jnc.13981">page 644</jats:ext-link>.</jats:p></jats:sec>