Stanford study reveals first whole-brain serotonin map in mice
- “It’s really giving us an overview of how serotonin views the brain.”
- That is how Liqun Luo describes a breakthrough that finally brings clarity to one of neuroscience's most elusive networks.
- To uncover this architecture, researchers used viral-genetic tracing and whole-brain imaging.
“It’s really giving us an overview of how serotonin views the brain.”
That is how Liqun Luo describes a breakthrough that finally brings clarity to one of neuroscience’s most elusive networks. Published in Cell, a new study reveals that the mouse brain’s expansive serotonin system—which plays a role in everything from mood to movement—is composed of five distinct groups of neurons that target functionally related brain regions.
Viral-Genetic Tracing Illuminates Five Distinct Projection Regions
To uncover this architecture, researchers used viral-genetic tracing and whole-brain imaging.
The team injected mice with a virus designed to make connected serotonin neurons light up throughout the brain. This allowed them to image all of the areas affected by the neurotransmitter from the dorsal and median raphe.
The analysis revealed five distinct projection regions:
- The hippocampal-entorhinal network
- The basal ganglia
- The cortical regions
- The medial interbrain (composed of the medial thalamus and hypothalamus)
- The brainstem and lateral thalamic nuclei
Mapping The Vertebrate Serotonin Connectome
The research provides the first whole-brain map of connections, or “projectome,” among serotonin neurons in a vertebrate.
While an independent team mapped the entire serotonin system in a roundworm in 2023, mapping the vertebrate system has historically proven difficult. Jeremiah Cohen, professor of neuroscience at the University of Minnesota who was not involved in the study, notes that understanding how and where serotonin neurons connect within the brain was previously “pretty hazy.”
“the anatomical scaffold that we can all use to try to understand this system more deeply.”
Jeremiah Cohen
Functional Organization Versus Physical Proximity
These groupings suggest that the serotonin system is organized by functional relatedness rather than sheer proximity to its targets.
Yet even among related brain regions, the projectome showed unexpected disconnects. For instance, the central amygdala and nearby basolateral amygdala, which both help regulate fear learning and emotion, belong to separate groups—a distinction that tracks with their separate developmental origins and cellular makeup.
Defining the Rules of a Complex Biological Beast
Liqun Luo, professor of neurobiology at Stanford University and study investigator, describes the serotonin system as a “complex beast,” adding that these connections help “define the rules of this complex world across multiple dimensions.”