In 1894, Ramony Cajal first proposed that memory is stored as an anatomical
change in the strength of neuronal connections. For the following 60 years
, little evidence was recruited in support of this idea. This situation cha
nged in the middle of the twentieth century with the development of cellula
r techniques for the study of synaptic connections and the emergence of new
formulations of synaptic plasticity that redefined Ramony Cajal's idea, ma
king it more suitable for testing. These formulations defined two categorie
s of plasticity referred to as homosynaptic or Hebbian activity-dependent,
and heterosynaptic or modulatory input-dependent. Here we suggest that Hebb
ian mechanisms are used primarily for learning and for short-term memory bu
t often cannot, by themselves, recruit the events required to maintain a lo
ng-term memory. In contrast, heterosynaptic plasticity commonly recruits lo
ng-term memory mechanisms that lead to transcription and to synaptic growth
. When jointly recruited, homosynaptic mechanisms assure that teaming is ef
fectively established and heterosynaptic mechanisms ensure that memory is m
aintained.