The mouse brain’s expansive serotonin system comprises five distinct groups of neurons that target functionally related brain regions, according to a study published in Cell. The research provides the first whole-brain map of connections, known as a projectome, among serotonin neurons in a vertebrate.
Mapping the Vertebrate Serotonin System With Viral Tracing
Although scientists have long recognized that serotonin neurons differ, getting a clear picture of their precise brain targets and pathways remained quite vague, notes Jeremiah Cohen, a neuroscience professor at the University of Minnesota who did not participate in the work. The new map reveals the nature and extent of these connections, serving as an anatomical scaffold that researchers can use to understand the system more deeply.
Building upon 2018 discoveries in mice, the investigators employed whole-brain imaging and viral-genetic tracing to map projections originating from the dorsal and median raphe serotonin neurons. Supported by the BRAIN Initiative, investigators injected mice with a virus designed to make connected serotonin neurons light up throughout the brain. They repeated the process until they had imaged all of the areas the neurotransmitter affects.
Five Distinct Projection Regions Identified in Mice
Analysis of the whole-brain images revealed five distinct projection regions among serotonin neurons. Comprising these categories are the cortical regions, the basal ganglia, the hippocampal-entorhinal network, the brainstem and lateral thalamic nuclei, and the medial interbrain, which consists of the hypothalamus and medial thalamus.
According to the investigators, these classifications indicate that functional relationships—rather than physical distance to target areas—dictate how the serotonin system is arranged. Yet even among related brain regions, the projectome showed some unexpected disconnects. For example, the central amygdala and nearby basolateral amygdala, which both help regulate fear learning and emotion, belong to separate groups. This difference tracks with their separate developmental origins and cellular makeup.
Liqun Luo, professor of neurobiology at Stanford University and a study investigator, notes that the work provides an overview of how serotonin views the brain. Describing the serotonin system as a complex beast, Luo states that these connections help define the rules of this complex world across multiple dimensions.
Frequently Asked Questions About the Mouse Brain Serotonin Projectome
What is a projectome in neuroscience?
A projectome is a comprehensive whole-brain map of physical connections among specific types of neurons. In this study, researchers created the first projectome for serotonin neurons in a vertebrate.
Which brain regions did the study identify as distinct serotonin targets?
The research identified five distinct projection regions: the hippocampal-entorhinal network, the basal ganglia, the cortical regions, the medial interbrain, and the brainstem and lateral thalamic nuclei.
What funding supported the serotonin mapping research?
The research team received support from the BRAIN Initiative to conduct their viral-genetic tracing and whole-brain imaging experiments in mice.
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