Cerebral Cortex, Vol. 12, No. 3, 329-337,
March 2002
© 2002 Oxford University Press
Aging Causes a Preferential Loss of Cholinergic Innervation of Characterized Neocortical Pyramidal Neurons
1 Departments of Pharmacology & Therapeutics and , 2 Anatomy & Cell Biology, McGill University, Montreal, Quebec, Canada, H3G 1Y6 and , 3 Neurobiologie Cellulaire Centre de recherche, Université Laval—Robert Giffard, Quebec, Quebec, Canada, G1J 2G3
Dr A. Claudio Cuello, Departments of Pharmacology & Therapeutics, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec H3G 1Y6, Canada. Email: accuello{at}pharma.mcgill.ca.
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.
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