In the last decade of the nineteenth century, Santiago
Ramón y Cajal introduced a theory of memory storage
in which information is stored in the brain by anatomi-
cal changes in the connections between neurons1. This
insight proved not only prescient but also premature.
Over the next sixty years, few experiments were directed
toward testing this idea. Indeed, during much of this
period, Ramón y Cajal’s suggestion was not even taken
seriously by many scientists working on the brain
because of opposition to the idea that the nervous sys-
tem could be studied effectively at the level of individual
cells and their connections2–5.
This situation began to change in the late 1940s and
early 1950s. Intracellular microelectrode recording
methods were introduced for studying the synaptic
actions of individual neurons and electron microscopy
was applied to visualize the fine structure of synapses.
These methodological advances allowed central synaps-
es to be studied directly and led to a revival of interest in
Ramón y Cajal’s ideas. In addition, the ideas were refor-
mulated in functional terms that made them more suit-
able to physiological and anatomical testing. These for-
mulations defined two broad categories of SYNAPTIC
PLASTICITY, generally referred to as homosynaptic and
heterosynaptic plasticity. In this review we will focus on
an extensively studied example of each type of synaptic
plasticity: Hebbian homosynaptic potentiation in the
hippocampus and heterosynaptic facilitation in Aplysia.
Homosynaptic and heterosynaptic rules
In 1949, Donald Hebb proposed a homosynaptic rule
for long-term memory on the basis of the strengthen-
ing of synaptic connections: the events responsible for
triggering synaptic strengthening occur at the same
synapse as is being strengthened (FIG. 1a)3. Specifically,
Hebb proposed that the strength of the connection
between the two neurons is increased for a long period
of time when the firing of the presynaptic and post-
synaptic neuron are closely correlated in time.