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 via OpenAlex
Summary
AI-generated from the abstractSerotonin (5-HT) is a key neuromodulator that directly influences plasticity at excitatory synapses on dendritic spines. It activates 14 subtypes of G-protein-coupled receptors, each with distinct expression and signaling. Disruptions in serotonergic transmission during development or adulthood cause lasting changes in behavior and neuronal structure, particularly in dendritic spines, indicating serotonin's critical role in excitatory synaptic plasticity. This review summarizes how 5-HT receptors contribute to the development and maturation of excitatory postsynaptic synapses, from spinogenesis through stabilization, potentiation, and depression. It also highlights recent advances showing how atypical serotonergic signaling and psychedelics alter spine structure and function.
Study at a glance
| Characteristics | Review Peer reviewed |
|---|---|
| Population | General (serotonin and synapse development) |
| Topics | Neuroplasticity Serotonin |
| Keywords | Excitatory postsynaptic potential Modulation music Excitatory synapse |
| Citations | 1 |
| Key finding | 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.