Complete morphologies of basal forebrain cholinergic neurons in the mouse

Elife. 2014 May 7:3:e02444. doi: 10.7554/eLife.02444.


The basal forebrain cholinergic system modulates neuronal excitability and vascular tone throughout the cerebral cortex and hippocampus. This system is severely affected in Alzheimer's disease (AD), and drug treatment to enhance cholinergic signaling is widely used as symptomatic therapy in AD. Defining the full morphologies of individual basal forebrain cholinergic neurons has, until now, been technically beyond reach due to their large axon arbor sizes. Using genetically-directed sparse labeling, we have characterized the complete morphologies of basal forebrain cholinergic neurons in the mouse. Individual arbors were observed to span multiple cortical columns, and to have >1000 branch points and total axon lengths up to 50 cm. In an AD model, cholinergic axons were slowly lost and there was an accumulation of axon-derived material in discrete puncta. Calculations based on published morphometric data indicate that basal forebrain cholinergic neurons in humans have a mean axon length of ∼100 meters.DOI:

Keywords: Alzheimer's disease; Cre; LoxP; axon arbor; cerebral cortex; neurodegeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / genetics
  • Alkaline Phosphatase / metabolism
  • Alzheimer Disease / pathology
  • Animals
  • Axons
  • Basal Forebrain / metabolism*
  • Bexarotene
  • Cell Line
  • Cholinergic Neurons / cytology
  • Cholinergic Neurons / metabolism*
  • Disease Models, Animal
  • Disease Progression
  • Hippocampus
  • Image Processing, Computer-Assisted
  • Mice
  • Mice, Knockout
  • Microscopy, Confocal
  • Tetrahydronaphthalenes / pharmacology


  • Tetrahydronaphthalenes
  • Bexarotene
  • Alkaline Phosphatase

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.