Neural plasticity in the ageing brain

REVIEWSStereological principles

A set of rules that allows

objective counting of the

number of objects in a threedimensional structure

independent of the size of the

objects. Among these is the

dissector principle, which

ensures that objects are

sampled with a probability that

is proportional to their number

and not their size.Ageing is associated with a decline in cognitive function

that can, in part, be explained by changes in neural

plasticity or cellular alterations that directly affect

mechanisms of plasticity. Although several age-related

neurological changes have been identified during normal ageing, these tend to be subtle compared with the

alterations that are observed in age-associated disorders,

such as Alzheimers disease and Parkinsons disease.

Moreover, understanding age-related changes in cognition sets a background against which it is possible to

assess the effects of pathological disease states.In this review, we discuss functional alterations that

occur during normal ageing in the medial temporal

lobe and the prefrontal cortex (PFC) and how these ageassociated changes might contribute to the selective cognitive impairments that occur in advanced age. We first

discuss data that suggest that profound loss of neurons

does not significantly contribute to age-related cognitive

impairments. We then review the subtle changes in neuronal morphology, cellcell interactions and gene expression that might contribute to alterations in plasticity in

aged animals and how these changes disrupt the network

dynamics of aged neuronal ensembles that ultimately

contribute to selective behavioural impairments.Morphology of the ageing brainAge-related changes in the morphology of neurons are

selective and it seems that there is no universal pattern

across the entire brain. However, one finding that does

seem to be consistent is that in most brain areas neuronal

loss does not have a significant role in age-related cognitive decline. Rather, small, region-specific changes in dendritic branching and spine density are more characteristic

of the effects of ageing on neuronal morphology (FIG. 1). This is contrary to early investigations of aged nervous

tissue in which profound neuron loss was reported to

occur in advanced age.In 1955, Brody was the first to suggest that age-related

reductions in brain weight were due, in part, to a decline

in neuron number in all cortical layers1. Subsequent

investigations corroborated this work, reporting a

1060% decline in cortical neuron density between late

childhood and...