A whole-brain atlas of inputs to serotonergic neurons of the dorsal and median raphe nuclei

Neuron. 2014 Aug 6;83(3):663-78. doi: 10.1016/j.neuron.2014.07.002.


The serotonin system is proposed to regulate physiology and behavior and to underlie mood disorders; nevertheless, the circuitry controlling serotonergic neurons remains uncharacterized. We therefore generated a comprehensive whole-brain atlas defining the monosynaptic inputs onto forebrain-projecting serotonergic neurons of dorsal versus median raphe based on a genetically restricted transsynaptic retrograde tracing strategy. We identified discrete inputs onto serotonergic neurons from forebrain and brainstem neurons, with specific inputs from hypothalamus, cortex, basal ganglia, and midbrain, displaying a greater than anticipated complexity and diversity in cell-type-specific connectivity. We identified and functionally confirmed monosynaptic glutamatergic inputs from prefrontal cortex and lateral habenula onto serotonergic neurons as well as a direct GABAergic input from striatal projection neurons. In summary, our findings emphasize the role of hyperdirect inputs to serotonergic neurons. Cell-type-specific classification of connectivity patterns will allow for further functional analysis of the diverse but specific inputs that control serotonergic neurons during behavior.

Publication types

  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Animals
  • Brain Mapping
  • Chromosome Pairing / physiology
  • Dorsal Raphe Nucleus / metabolism*
  • Mice
  • Nerve Tissue / metabolism
  • Neural Pathways / metabolism
  • Serotonergic Neurons / cytology*
  • Serotonergic Neurons / metabolism
  • Serotonin / metabolism*


  • Serotonin