Human Physiology, 14th edition (2016)

The Central Nervous System 223

The rise in the intracellular Ca^2 1 concentration also
causes longer-term changes in the postsynaptic neuron. These
more persistent changes needed for synaptic plasticity and the
formation of long-term memories require Ca^2 1 to enter the
nucleus and, bound to calmodulin, activate a different protein
kinase. This enzyme, in turn, activates a transcription factor
known as CREB (for “cyclic AMP response element binding
protein”). CREB and other transcription factors activate genes
that produce new mRNA and proteins. In addition, there are
epigenetic changes—including histone protein acetylation
and DNA methylation—that influence genetic transcription
(chapter 3, section 3.5). In particular, histone acetylation,
which makes the DNA assume a less compacted form that
allows genetic transcription, is increased by LTP. Such epi-
genetic changes may contribute to long-term memory.
Pyramidal neurons (a type of neuron characteristic of the
cerebral cortex, hippocampus and amygdala) have thousands
of dendritic spines ( fig.  8.17 ) where most of the EPSPs are
produced. Dendritic spines grow and the spine heads enlarge
during LTP. The spines that grow are selectively stabilized dur-
ing subsequent training, so that they persist long after the train-
ing has stopped. These changes are associated with increased
numbers of AMPA receptors in the postsynaptic membrane
and increased synaptic strength. During long-term depression
(LTD), by contrast, dendritic spines have been observed to
shrink or disappear. This is accompanied by the loss of AMPA

NMDA

Na+ Na+Ca2+ receptor

AMPA

receptor

LT P

induction

Postsynaptic membrane

of dendrite

Glutamate

Presynaptic axon

Ca2+

Nitric CaMKII

oxide

as retrograde

messenger

1. Glutamate binds to
   AMPA and NMDA
   receptors


2. Increased release
   of glutamate from
   presynaptic axon


3. Increased Na+
   diffusion through
   more AMPA
   receptors Ca
   2+ goes through
   NMDA receptors into
   cytoplasm, activates
   CaMKII

2.

Figure 8.16 Some proposed mechanisms

responsible for long-term potentiation (LTP). The

neurotransmitter glutamate can bind to two different

receptors, designated AMPA and NMDA. The activation

of the NMDA receptors promotes an increased

concentration of Ca^2 1 in the cytoplasm, which is needed

in order for LTP to be induced. LTP is believed to be a

mechanism of learning at the level of the single synapse.

(CaMKII 5 calcium/calmodulin-dependent protein

kinase II).

Figure 8.17 A rendering of a pyramidal neuron

with numerous dendritic spines. Presynaptic axons make

synapses with these dendritic spines.