Two major network domains in the dorsal raphe nucleus

J Comp Neurol. 2015 Jul 1;523(10):1488-504. doi: 10.1002/cne.23748. Epub 2015 Mar 16.


Serotonin neurons in the dorsal and median raphe nuclei (DR and MR) are clustered into heterogeneous groups that give rise to topographically organized forebrain projections. However, a compelling definition of the key subgroups of serotonin neurons within these areas has remained elusive. In order to be functionally distinct, neurons must participate in distinct networks. Therefore, we analyzed subregions of the DR and MR by their afferent input. Clustering methods and principal component analysis were applied in mouse to anterograde tract-tracing experiments available from the Allen Mouse Brain Connectivity Atlas. The results revealed a major break in the networks of the DR such that the caudal third of the DR was more similar in afferent innervation to the MR than it was to the rostral two-thirds of the DR. The rostral part of the DR is associated with networks controlling motor and motivated behavior, while the caudal DR is more closely aligned with regions that regulate rhythmic hippocampal activity. Thus, a major source of heterogeneity within the DR is inclusion of the caudal component, which may be more accurately viewed as a dorsal extension of the MR.

Keywords: RRID:nif-0000-00362; RRID:nif-0000-30467; RRID:nlx_146253; depression; dorsal raphe; median raphe; mood; serotonin; tract-tracing.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Afferent Pathways / physiology*
  • Animals
  • Biotin / analogs & derivatives
  • Biotin / metabolism
  • Cluster Analysis
  • Dextrans / metabolism
  • Efferent Pathways / physiology*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neurons / metabolism
  • RNA, Messenger / metabolism
  • Raphe Nuclei / cytology*
  • Raphe Nuclei / metabolism*
  • Serotonin / metabolism
  • Synapsins / genetics
  • Synapsins / metabolism
  • Tryptophan Hydroxylase / genetics
  • Tryptophan Hydroxylase / metabolism


  • Dextrans
  • RNA, Messenger
  • Synapsins
  • biotinylated dextran amine
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • Serotonin
  • Biotin
  • Tph2 protein, mouse
  • Tryptophan Hydroxylase