The serotonin receptor 7 and the structural plasticity of brain circuits

Abstract

Serotonin (5-hydroxytryptamine, 5-HT) modulates numerous physiological processes in the nervous system. Together with its function as neurotransmitter, 5-HT regulates neurite outgrowth, dendritic spine shape and density, growth cone motility and synapse formation during development. In the mammalian brain 5-HT innervation is virtually ubiquitous and the diversity and specificity of its signaling and function arise from at least 20 different receptors, grouped in 7 classes. Here we will focus on the role 5-HT7 receptor (5-HT7R) in the correct establishment of neuronal cytoarchitecture during development, as also suggested by its involvement in several neurodevelopmental disorders. The emerging picture shows that this receptor is a key player contributing not only to shape brain networks during development but also to remodel neuronal wiring in the mature brain, thus controlling cognitive and emotional responses. The activation of 5-HT7R might be one of the mechanisms underlying the ability of the CNS to respond to different stimuli by modulation of its circuit configuration.

Orbitofrontal cortex 5-HT2A receptor mediates chronic stress-induced depressive-like behaviors and alterations of spine density and Kalirin7

“…Abnormal architecture of dendritic spines is associated with many mental disorders (Fenelon et al, 2013, Licznerski andDuman, 2013). Chronic stress regulated dendritic material in the OFC (Liston et al, 2006), and there are some evidence that 5-HT and its receptors regulate dendritic spine shape and spine density during development (Yoshida et al, 2011, Mogha et al, 2012, Volpicelli et al, 2014. In chronically restraint stressed rats, a decrement of 5-HT 2A receptor-mediated EPSCs in the mPFC pyramidal neurons (Aghajanian and Marek, 1997) correlated with atrophy of the apical dendrites and decreased spine density in this region (Liu and Aghajanian, 2008).…”

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

“…The involvement of 5-HT7R in fear conditioning has been demonstrated in 5-HT7R KO mice, which displayed impaired contextual fear conditioning along with decreased longterm synaptic plasticity within the CA1 region of the hippocampus (Roberts et al, 2004). Based on preclinical findings, 5-HT7Rs are now emerging as a possible therapeutic target for the treatment of cognitive disorders and depression (Gasbarri et al, 2008, Matthys et al, 2011and Volpicelli et al, 2014. For example, treatment with selective 5-HT7R antagonists has been shown to have anxiolitic and antidepressant effects in mice tested in the forced swim and tail suspension tests (Nikiforuk, 2015).…”

Serotonin 5‐HT7 receptor increases the density of dendritic spines and facilitates synaptogenesis in forebrain neurons

“…Accordingly, accumulating data suggest an important role for the 5‐HT7R in regulation of structural plasticity of brain circuits (Volpicelli et al . ; Wirth et al . ).…”