Basal forebrain cholinergic neurons are selectively vulnerable to AMPA/kainate receptor-mediated neurotoxicity

Neuroscience. 1994 Jun;60(3):659-64. doi: 10.1016/0306-4522(94)90494-4.


We exposed murine basal forebrain neuronal cultures for 24 h to defined concentrations of N-methyl-D-aspartate, kainate or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate, and assessed the resultant degeneration of the cholinergic neuronal subpopulation, as identified by choline acetyltransferase immunocytochemistry and acetylcholinesterase histochemistry. Cholinergic neurons, representing about 0.5% of the total neuronal population, were atypically vulnerable to excitotoxins. Compared to most basal forebrain neurons, they were more vulnerable to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate/kainate receptor-mediated injury and slightly less vulnerable to N-methyl-D-aspartate receptor-mediated injury. The present findings provide quantitative demonstration of a mechanism that preferentially injures basal forebrain cholinergic neurons, and may thus suggest candidate factors pertaining to their loss in disease states like Alzheimer's disease.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylcholine*
  • Acetylcholinesterase / analysis
  • Alzheimer Disease / metabolism
  • Animals
  • Cells, Cultured
  • Choline O-Acetyltransferase / analysis
  • Kainic Acid / toxicity*
  • Mice
  • N-Methylaspartate / toxicity*
  • Nerve Tissue Proteins / analysis
  • Neurons / drug effects*
  • Prosencephalon / cytology
  • Prosencephalon / drug effects*
  • Prosencephalon / embryology
  • Receptors, AMPA / drug effects*
  • Receptors, AMPA / physiology
  • Receptors, Kainic Acid / drug effects*
  • Receptors, Kainic Acid / physiology
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / toxicity*


  • Nerve Tissue Proteins
  • Receptors, AMPA
  • Receptors, Kainic Acid
  • N-Methylaspartate
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
  • Choline O-Acetyltransferase
  • Acetylcholinesterase
  • Acetylcholine
  • Kainic Acid