Individual mediodorsal thalamic neurons project to multiple areas of the rat prefrontal cortex: A single neuron-tracing study using virus vectors

J Comp Neurol. 2017 Jan 1;525(1):166-185. doi: 10.1002/cne.24054. Epub 2016 Jul 14.


The prefrontal cortex has an important role in a variety of cognitive and executive processes, and is generally defined by its reciprocal connections with the mediodorsal thalamic nucleus (MD). The rat MD is mainly subdivided into three segments, the medial (MDm), central (MDc), and lateral (MDl) divisions, on the basis of the cytoarchitecture and chemoarchitecture. The MD segments are known to topographically project to multiple prefrontal areas at the population level: the MDm mainly to the prelimbic, infralimbic, and agranular insular areas; the MDc to the orbital and agranular insular areas; and the MDl to the prelimbic and anterior cingulate areas. However, it is unknown whether individual MD neurons project to single or multiple prefrontal cortical areas. In the present study, we visualized individual MD neurons with Sindbis virus vectors, and reconstructed whole structures of MD neurons. While the main cortical projection targets of MDm, MDc, and MDl neurons were generally consistent with those of previous results, it was found that individual MD neurons sent their axon fibers to multiple prefrontal areas, and displayed various projection patterns in the target areas. Furthermore, the axons of single MD neurons were not homogeneously spread, but were rather distributed to form patchy axon arbors approximately 1 mm in diameter. The multiple-area projections and patchy axon arbors of single MD neurons might be able to coactivate cortical neuron groups in distant prefrontal areas simultaneously. Furthermore, considerable heterogeneity of the projection patterns is likely, to recruit the different sets of cortical neurons, and thus contributes to a variety of prefrontal functions. J. Comp. Neurol. 525:166-185, 2017. © 2016 Wiley Periodicals, Inc.

Keywords: RRID: AB_476894; Sindbis virus vector; axonal arborization; mediodorsal nucleus; middle layer; prefrontal areas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Genetic Vectors
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Immunoenzyme Techniques
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Male
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • Neural Pathways / cytology
  • Neural Pathways / metabolism
  • Neuroanatomical Tract-Tracing Techniques
  • Neurons / cytology*
  • Neurons / metabolism
  • Prefrontal Cortex / cytology*
  • Prefrontal Cortex / metabolism
  • Rats, Sprague-Dawley
  • Red Fluorescent Protein
  • Sindbis Virus / genetics
  • Thalamus / cytology*
  • Thalamus / metabolism


  • Luminescent Proteins
  • Green Fluorescent Proteins