Synapses - Quantitative Neurophysiology - page 74

memory could be encoded in the strength of the connections between neurons. By strength, Hebb meant
that the pre-synapse could have a greater impact (either excitatory or inhibitory) on the post-synaptic
membrane. Given all of the ways that drugs and diseases can act on the synapse, it is possible for natural
changes in synaptic strength to be accomplished by any or all of these mechanisms.
The ability of a synaptic strength to change is called synaptic plasticity .The mechanism of plasticity
is one of the most elusive questions in neurobiology because of the many factors that could play a role.
What is known is that some molecular level change occurs at either the pre-synapse, post-synapse or
neurotransmitter clearance. For example, if a receptor channel on the post-synapse is over expressed, i.e.,
more channels waiting to bind with a neurotransmitter) the post-synapse will become more sensitive to
the concentration of neurotransmitter and be less susceptible to saturation.The most simple way to model
synaptic plasticity is to change g syn in Eq. (6.3). The interpretation is that the value of g syn is related to
the number of synaptic ion channels. The opposite is true if the receptor channel is under expressed.
Hebb also proposed a mechanism by which synapses would be triggered to change, elegantly
expressed in the phrase neurons that fire together are wired together . In other words, the more two neurons
fire at the same time, the more tightly they will be connected.These types of synapses were in fact found to
exist and were given the name Hebbian synapses . Recent studies, however, have shown that there are other
reasons that neurons may either connect or disconnect, including pH, ion concentration, or drug use.
One of the most interesting ways for synapses to change is the phenomenon of Long Term Poten-
tiation (LTP) discovered by Jerje Lomo in 1966. A typical experiment has three phases that are shown in
Fig. 6.3. First, an external stimulus is applied to one neuron, which fires an action potential. This action
potential releases neurotransmitter which crosses the synaptic cleft and induces a depolarization in the
post-synapse of a second neuron. The recorded EPSP, V post

1 serves as a baseline. Second, a rapid train of
stimuli are applied to the first neuron.The number of stimuli and rate is variable but is typically performed
over a period of minutes. Third, at some later time a single stimulus is applied to neuron one and V post
2

is

recorded. Surprisingly, the response has been potentiated ,or V post
2

>V post

1 . The interpretation is that the
post-synapse has become more sensitive to activity at the pre-synapse, or in other words, the connection
has become strengthened. Even more surprising is that this effect may last many weeks or even months.
Understanding the mechanism of LTP is a very active area of research since is a controlled way to study
how synaptic strength changes.