Serotonergic modulation of excitatory synapse development and plasticity
Victoria N. Chang, Roberto Ogelman, R. Vargas, Won Chan Oh
Molecules and Cells March 10, 2026 Peer reviewed DOI: 10.1016/j.mocell.2026.100346 via OpenAlex
Summary
Serotonin (5-HT) plays a crucial role in the modulation of excitatory synapse plasticity at dendritic spines by activating various G-protein-coupled receptors. Disruptions in serotonergic transmission can lead to significant behavioral and neuronal changes, impacting dendritic spine structure and function. This review discusses how different 5-HT receptors influence the life cycle of dendritic spines, from their formation to stabilization and depression, and examines recent findings on how atypical serotonergic signaling and psychedelics affect these processes.
Study at a glance
| Design | review |
|---|---|
| Key finding | Serotonin receptors are critical for the development and maturation of excitatory postsynaptic synapses, affecting the structural and functional properties of dendritic spines. |
Abstract
Excitatory synapse plasticity at postsynaptic dendritic spines is directly modulated through neurotransmitter signaling. Serotonin (5-HT) is a primary neuromodulator in the brain that activates 14 subtypes of G-protein-coupled receptors, each with distinct expression patterns and downstream signaling mechanisms. Disruptions of serotonergic transmission during development and adulthood induce long-lasting behavioral and neuronal changes, often characterized by profound alterations in the structure and function of dendritic spines, suggesting 5-HT plays a critical role in excitatory synaptic plasticity. This review summarizes research demonstrating the importance of 5-HT receptors in the development and maturation of excitatory postsynaptic synapses. We focus on 5-HT receptor-mediated signaling and how different 5-HT receptors influence the various stages in the lifetime of a dendritic spine from spinogenesis to stabilization, potentiation, and depression. Finally, we highlight recent advances from the past decade in 5-HT research, focusing on how atypical serotonergic signaling alters excitatory synapse plasticity and how serotonergic psychedelics affect dendritic spine structure and function.