FoundationalConceptsNeuroscience

sions to be sufficiently similar in shape to some portion of the THC
molecule, so that they all can act as agonists at the same receptor—the
interaction of an agonist with a receptor is all about shape, just like a
key inserted into a lock.
Because CB receptors and endocannabinoids are widespread in the
brain, they no doubt serve important functions. What might these
be? As it turns out, CB receptors appear to be largely present on the
presynaptic axon terminals of neurons. And the endocannabinoid
molecules appear to be synthesized and released from postsynaptic
dendrites in response to glutamatergic stimulation. The endo-
cannabinoid then travels across the synaptic cleft to interact with CB
receptors on presynaptic axon terminals. The CB receptors may be on
the axon terminal of the neuron that originally released the glutamate
neurotransmitter, or they may be on axon terminals of other nearby
neurons, or they may be on nearby astrocyte glial cells. A key point
here is the backward, or retro, nature of the signaling. Endocannabi-
noids are examples of retrograde neurotransmitters, molecules that
carry signal information in the direction opposite from the way neu-
ral signals were generally thought to move.
Retrograde neurotransmission occurs at a very large number of
chemical synapses in the brain, probably trillions of synapses. It is
thought that retrograde signaling by endocannabinoids is intimately
involved in the dynamic tuning of the strengths of synapses—the in-
tensity of the signal transmission from one cell to the next. This tun-
ing of synaptic strength is an aspect of neuroplasticity—the capacity of
neural circuitry to alter its properties. The English word plastic derives
from the Greek plassein, meaning “to mold or form.” Neuroplasticity is
a dynamic phenomenon that occurs throughout one’s entire life and is
believed to underlie, for example, all of learning and memory forma-
tion (see Chapter 19). Wiring and rewiring are happening all the time.