Synaptic Plasticity — The Brain's Response
to Experience
One of the most fascinating and important
properties of the mammalian brain is its plasticity.
Plasticity refers to the ability of experience, whether
it be learning in a classroom, a stressful event, or
ingestion of a drug, to modify the organization and
behavior of neural circuits in the brain. Experience-
dependent brain plasticity is in large part due to long-lasting,
activity- dependent changes in the strength of communication
at excitatory synapses, that is synaptic plasticity.
The most well-understood forms of synaptic
plasticity are termed long- term potentiation (LTP)
and long-term depression (LTD) and these have been studied
most extensively in the hippocampus, a region of the
brain known to be important for a number of different
forms of learning and memory. LTP, which refers to a
long- lasting increase in synaptic strength, and LTD,
which refers to a long- lasting decrease in synaptic
strength, are triggered by different patterns of neural
activity that lead to the activation of a specific subtype
of receptor for the neurotransmitter glutamate, termed
an NMDA receptor. When activated, the NMDA receptor
lets calcium enter the cell and depending on the detailed
characteristics of this calcium signal, different intracellular
signaling cascades are activated leading to LTP or LTD.
Specifically LTP involves activation of specialized
enzymes (termed protein kinases) while LTD involves
activation of enzymes (termed protein phosphatases).
These enzymes then modify a different family of glutamate
receptors (termed AMPA receptors) and it is this modification
of AMPA receptors that directly leads to LTP or LTD.
Indeed, LTP and LTD may be the first steps leading to
structural changes in the brain, specifically the formation
of new synaptic connections (LTP) or the elimination
of pre-existing synaptic contacts (LTD).
How do we know LTP and LTD are really
important for brain plasticity? Work from a number of
laboratories has shown that drugs or genetic manipulations
that prevent LTP and/ or LTD also routinely impair many
different forms of learning and memory. Indeed, these
forms of synaptic plasticity may also play an important
role in certain disease states. For example, drugs of
abuse such as cocaine modify the strength of excitatory
synapses in certain key brain regions known to be involved
in addiction. Thus in addition to being important for
adaptive forms of experience-dependent plasticity, synaptic
plasticity may also play an important role in the etiology
of pathological behaviors such as addiction.
