CHAPTER 19
Learning, Memory, Language, & Speech 291SYNAPTIC PLASTICITY & LEARNING
Short- and long-term changes in synaptic function can occur
as a result of the history of discharge at a synapse; that is, syn-
aptic conduction can be strengthened or weakened on the ba-
sis of past experience. These changes are of great interest
because they represent forms of learning and memory. They
can be presynaptic or postsynaptic in location.
One form of plastic change is
posttetanic potentiation,
the
production of enhanced postsynaptic potentials in response
to stimulation. This enhancement lasts up to 60 seconds and
occurs after a brief (tetanizing) train of stimuli in the presyn-
aptic neuron. The tetanizing stimulation causes Ca
2+
to accu-
mulate in the presynaptic neuron to such a degree that the
intracellular binding sites that keep cytoplasmic Ca
2+
low are
overwhelmed.
Habituation
is a simple form of learning in which a neutral
stimulus is repeated many times. The first time it is applied it is
novel and evokes a reaction (the orienting reflex or “what is it?”
response). However, it evokes less and less electrical response as
it is repeated. Eventually, the subject becomes habituated to the
stimulus and ignores it. This is associated with decreased
release of neurotransmitter from the presynaptic terminal
because of decreased intracellular Ca
2+. The decrease in intra-
cellular Ca
2+
is due to a gradual inactivation of Ca
2+
channels. It
can be short term, or it can be prolonged if exposure to the
benign stimulus is repeated many times. Habituation is a classic
example of nonassociative learning.
Sensitization
is in a sense the opposite of habituation. Sensi-
tization is the prolonged occurrence of augmented postsynaptic
responses after a stimulus to which one has become habituated
is paired once or several times with a noxious stimulus. At least
in the sea snail
Aplysia,
the noxious stimulus causes discharge
of serotonergic neurons that end on the presynaptic endings of
sensory neurons. Thus, sensitization is due to presynaptic facil-
itation. Sensitization may occur as a transient response, or if it
is reinforced by additional pairings of the noxious stimulus and
the initial stimulus, it can exhibit features of short-term or long-
term memory. The short-term prolongation of sensitization is
due to a Ca
2+
-mediated change in adenylyl cyclase that leads to
a greater production of cAMP. The long-term potentiation also
involves protein synthesis and growth of the presynaptic and
postsynaptic neurons and their connections.
Long-term potentiation (LTP)
is a rapidly developing per-
sistent enhancement of the postsynaptic potential response to
presynaptic stimulation after a brief period of rapidly repeated
stimulation of the presynaptic neuron. It resembles posttetanic
potentiation but is much more prolonged and can last for days.
Unlike posttetanic potentiation, it is initiated by an increase in
intracellular Ca
2+
in the postsynaptic rather than the presynap-
tic neuron. It occurs in many parts of the nervous system but
has been studied in greatest detail in the hippocampus.
There are two forms in the hippocampus: mossy fiber LTP,
which is presynaptic and independent of
N
-methyl-D-aspartate
(NMDA) receptors; and Schaffer collateral LTP, which is
postsynaptic and NMDA receptor-dependent. The hypotheti-
cal basis of the latter form is summarized in Figure 19–3. The
basis of mossy fiber LTP is unsettled, although it appears to
include cAMP and I
h
, a hyperpolarization-activated cation
channel. Other parts of the nervous system have not been as
well studied, but it is interesting that NMDA-independent LTP
can be produced in GABAergic neurons in the amygdala.
Long-term depression (LTD)
was first noted in the hippo-
campus but was subsequently shown to be present through-
out the brain in the same fibers as LTP. LTD is the opposite of
LTP. It resembles LTP in many ways, but it is characterized by
a decrease in synaptic strength. It is produced by slower stim-
ulation of presynaptic neurons and is associated with a
smaller rise in intracellular Ca
2+
than occurs in LTP. In the
cerebellum, its occurrence appears to require the phosphory-
lation of the GluR2 subunit of the
α
-amino-3-hydroxy-5-
methylisoxazole-4 propionic acid (AMPA) receptors. It may
be involved in the mechanism by which learning occurs in
the cerebellum.
CLINICAL BOX 19–1
The Case of HM: Defining a Link
between Brain Function & Memory
HM is an anonymous patient who suffered from bilateral
temporal lobe seizures that began following a bicycle acci-
dent at age 9. His case has been studied by many scientists
and has led to a greater understanding of the link between
the
temporal lobe
and
declarative memory.
HM had par-
tial seizures for many years, and then several tonic-clonic sei-
zures by age 16. In 1953, at the age of 27, HM underwent bi-
lateral surgical removal of the amygdala, large portions of
the hippocampal formation, and portions of the association
area of the temporal cortex. HM’s seizures were better con-
trolled after surgery, but removal of the temporal lobes led
to devastating memory deficits. He maintained
long-term
memory
for events that occurred prior to surgery, but he
suffered from
anterograde amnesia.
His
short-term mem-
ory
was intact, but he could not commit new events to long-
term memory. He had normal procedural memory, and he
could learn new puzzles and motor tasks. His case is the first
to bring attention to the critical role of temporal lobes in for-
mation of long-term declarative memories and to implicate
this region in the conversion of short-term to long-term
memories. Later work showed that the
hippocampus
is the
primary structure within the temporal lobe involved in this
conversion. Because HM retained memories from before sur-
gery, his case also shows that the hippocampus is not in-
volved in the storage of declarative memory. An audio-record-
ing from the 1990s of HM talking to scientists was released in
2007 and is available at http://www.npr.org/templates/story/
story.php?storyId=7584970.