The last decade has witnessed a significant turn in our understanding of th
e mechanisms responsible for the decline of cognitive functions in aged bra
in. As has been demonstrated by detailed morphological reassessments, the s
enescence-related changes in cognition cannot be attributed to a simple dec
rease in the number of neurons. It is becoming clearer that a major cause o
f age-induced deterioration of brain capability involves much subtler chang
es at the level of synapses. These changes are either morphological, i.e. r
eduction in the number of effective synapses and/or functional alterations,
i.e. changes in the efficacy of remaining synapses. Important questions ar
e now raised regarding the mechanisms which mediate these synaptic changes.
Clearly, an important candidate is calcium, the cytotoxic role of which is
already firmly established. The wealth of evidence collected so far regard
ing the changes of Ca2+ homeostasis in aged neurons shows that the overall
duration of cytoplasmic Ca2+ signals becomes longer. This is the most consi
stent result, demonstrated on different preparations and using different te
chniques. What is not yet clear is the underlying mechanism, as this result
could be explained either through an increased Ca2+ influx or because of a
deficit in the Ca2+ buffering/clearance systems. It is conceivable that th
ese prolonged Ca2+ signals may exert a local excitotoxic effect, removing p
referentially the most active synapses. Uncovering of the role of Ca2+ in t
he synaptic function of the aged brain presents an exciting challenge for a
ll those involved in the neurobiology of the senescent CNS.