Aging causes a preferential loss of cholinergic innervation of characterized neocortical pyramidal neurons

Cereb Cortex. 2002 Mar;12(3):329-37. doi: 10.1093/cercor/12.3.329.


Aging is known to markedly affect the number and structural characteristics of both pre- and post-synaptic sites in the cerebral cortex. There is evidence that lamina V pyramidal neurons, and their basilar dendrites in particular, are affected by age-related decline. Furthermore, layer V is the area where the greatest overall age- related losses in the total population of synaptic boutons and of cholinergic boutons are observed. Since both pyramidal neurons and cortical cholinergic input are characteristically compromised in aging, we investigated whether aging altered the pattern of cholinergic boutons in apposition to the soma, proximal and distal basal dendrites of intracellularly labeled lamina V large pyramidal neurons in the parietal cortex of young and aged rats. We observed a significant age-related decrease in the population of both total and cholinergic boutons apposed to proximal and distal dendrites of layer V large pyramidal neurons. However, the age-related decreases of cholinergic presynaptic boutons were higher than those in the total bouton population apposed to the pyramidal neurons. The average decrease in cholinergic boutons in aged rats was 3.7-fold more pronounced than the diminution in the overall number of presynaptic boutons. Our results add important new evidence in support of the concept that the age-related learning and memory deficits are attributable, at least partially, to a decline in the functional integrity of the forebrain cholinergic systems.

Publication types

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

MeSH terms

  • Aging / pathology*
  • Animals
  • Carrier Proteins / analysis
  • Cholinergic Fibers / chemistry
  • Cholinergic Fibers / pathology*
  • Cholinergic Fibers / ultrastructure
  • Immunohistochemistry
  • Membrane Transport Proteins*
  • Microscopy, Electron
  • Microtomy
  • Neocortex / pathology*
  • Neocortex / physiology
  • Patch-Clamp Techniques
  • Presynaptic Terminals / chemistry
  • Presynaptic Terminals / pathology
  • Presynaptic Terminals / ultrastructure
  • Pyramidal Cells / chemistry
  • Pyramidal Cells / pathology*
  • Pyramidal Cells / ultrastructure
  • Rats
  • Rats, Inbred BN
  • Rats, Inbred F344
  • Tissue Fixation
  • Vesicular Acetylcholine Transport Proteins
  • Vesicular Transport Proteins*


  • Carrier Proteins
  • Membrane Transport Proteins
  • Slc18a3 protein, rat
  • Vesicular Acetylcholine Transport Proteins
  • Vesicular Transport Proteins