Serotonergic modulation of excitatory synapse development and plasticity
Victoria N. Chang, Roberto Ogelman, R. Vargas, Won Chan Oh
Molecules and Cells March 10, 2026 DOI: 10.1016/j.mocell.2026.100346 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Population | General (serotonin and synapse development) |
| Topics | Neuroplasticity Serotonin |
| Keywords | Excitatory postsynaptic potential Modulation music Excitatory synapse Nonsynaptic plasticity |
| Citations | 1 |
| Key findings | Serotonin signaling through its various receptor subtypes plays a critical role in the development, maturation, and plasticity of excitatory synapses on 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.