A whole-brain map of long-range inputs to GABAergic interneurons in the mouse medial prefrontal cortex

Nat Neurosci. 2019 Aug;22(8):1357-1370. doi: 10.1038/s41593-019-0429-9. Epub 2019 Jul 8.


The medial prefrontal cortex (mPFC) contains populations of GABAergic interneurons that play different roles in cognition and emotion. Their local and long-range inputs are incompletely understood. We used monosynaptic rabies viral tracers in combination with fluorescence micro-optical sectioning tomography to generate a whole-brain atlas of direct long-range inputs to GABAergic interneurons in the mPFC of male mice. We discovered that three subtypes of GABAergic interneurons in two areas of the mPFC are innervated by same upstream areas. Input from subcortical upstream areas includes cholinergic neurons from the basal forebrain and serotonergic neurons (which co-release glutamate) from the raphe nuclei. Reconstruction of single-neuron morphology revealed novel substantia innominata-anteromedial thalamic nucleus-mPFC and striatum-anteromedial thalamic nucleus-mPFC circuits. Based on the projection logic of individual neurons, we classified cortical and hippocampal input neurons into several types. This atlas provides the anatomical foundation for understanding the functional organization of the mPFC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Mapping / methods*
  • Cell Count
  • Hippocampus / cytology
  • Hippocampus / physiology
  • Interneurons / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Parasympathetic Nervous System / cytology
  • Parasympathetic Nervous System / physiology
  • Prefrontal Cortex / anatomy & histology*
  • Prefrontal Cortex / cytology*
  • Prosencephalon / anatomy & histology
  • Prosencephalon / cytology
  • Raphe Nuclei / cytology
  • Raphe Nuclei / physiology
  • Serotonergic Neurons / physiology
  • Thalamus / cytology
  • Thalamus / physiology
  • gamma-Aminobutyric Acid / physiology*


  • gamma-Aminobutyric Acid