Regulation and Integration of the Body
Te number and size of presynaptic terminals may increase.
Presynaptic neurons release more neurotransmitter.
Each of these changes is an aspect of
, a persistent increase in synaptic strength that has been
shown to be crucial for memory formation. L±P was ﬁrst iden-
tiﬁed in hippocampal neurons that use the amino acid gluta-
mate as a neurotransmitter. One kind of glutamate receptor, the
, can act as a calcium channel and initiate the
cellular changes that bring about L±P.
Normally, NMDA receptors are blocked, preventing calcium
entry. When glutamate binds to diﬀerent receptors and depolar-
izes the postsynaptic terminal, as would happen upon the rapid
arrival of action potentials at the synapse, this NMDA block is
removed and calcium ﬂows into the postsynaptic cell.
Calcium inﬂux activates enzymes that carry out two main
Te enzymes modify the proteins in the postsynaptic termi-
nal, and also in the presynaptic terminal via retrograde mes-
sengers such as nitric oxide and endocannabinoids. Tese
changes strengthen the response to subsequent stimuli.
Tey activate genes in the postsynaptic neuron’s nucleus, which
leads to synthesis of synaptic proteins. Te molecular messenger
that alerts the nucleus that more protein is needed is a molecule
called CREB (cAMP response-element binding protein). A
neurotrophic factor called BDNF (brain-derived neurotrophic
factor) is required for the protein synthesis phase of L±P.
±ogether, these changes create long-lasting increases in synaptic
strength that are believed to underlie memory.
Te events underlying memory at a cellular level suggest
several approaches to enhancing memory formation. Currently
several drugs to improve memory are undergoing clinical trials.
Among these are drugs that enhance CREB production—the
more CREB, the more protein synthesis and the stronger the
Check Your Understanding
Name three factors that can enhance transfer of information
from STM to LTM.
Which functional areas of the cerebrum are involved in the
formation of procedural (skills) memory, but not involved in
For answers, see Appendix H.
Protection of the Brain
Describe how meninges, cerebrospinal ﬂuid, and the blood
brain barrier protect the CNS.
Explain how cerebrospinal ﬂuid is formed and describe its
Nervous tissue is so² and delicate, and even slight pressure
can injure neurons. However, the brain is protected by bone
(the skull), membranes (the meninges), and a watery cushion
When sensory input is processed in the association corti-
ces, the cortical neurons dispatch impulses to the medial tem-
poral lobe, which includes the hippocampus and surrounding
temporal cortical areas. Tese temporal lobe areas play a
major role in memory consolidation and memory access by
communicating with the thalamus and the prefrontal cortex.
Te prefrontal cortex and medial temporal lobe receive input
from acetylcholine-releasing neurons in the basal forebrain.
Te sprinkling of acetylcholine (ACh) onto these structures
is thought to prime them to allow the formation of memories.
Te loss of this ACh input, for example in Alzheimer’s dis-
ease, seems to disrupt both the formation of new memories
and the retrieval of old ones. Memories are retrieved when the
same sets of neurons that were initially involved in forming
the memories are stimulated.
Damage to the hippocampus and surrounding medial temporal
lobe structures on either side results in only slight memory loss,
but bilateral destruction causes widespread amnesia. Consoli-
dated memories are not lost, but new sensory inputs cannot be
associated with old, and the person lives in the here and now
from that point on. Tis condition is called
), in contrast to
, which is the
loss of memories formed in the distant past. You could carry on
an animated conversation with a person with anterograde am-
nesia, excuse yourself, return ﬁve minutes later, and that person
would not remember you.
Individuals suﬀering from anterograde amnesia can still
learn skills such as drawing, so procedural memory must in-
volve a diﬀerent learning circuit. As Figure 12.21b shows, the
basal nuclei (pink) are key players for procedural memory. Sen-
sory and motor inputs pass through the association cortex to
the basal nuclei. Tese inputs are then relayed via the thalamus
to the premotor cortex. Note that the basal nuclei receive in-
put from dopamine-releasing neurons in the substantia nigra of
the midbrain. Just as acetylcholine is necessary for declarative
memory, dopamine appears to be necessary for this procedural
memory circuit to function. Te loss of this dopamine input, as
in Parkinson’s disease, interferes with procedural memory.
Te two other kinds of nondeclarative memory involve yet
other brain regions. Te cerebellum is involved in motor mem-
ory, while the amygdaloid body is crucial for emotional memory
(see Figure 12.16). We will not describe these pathways here.
Molecular Basis of Memory
What happens at the molecular level when we form memories?
Human memory is notoriously diﬃcult to study. Animal ex-
perimental studies reveal that during learning:
Neuronal RNA content is altered and newly synthesized
mRNAs are delivered to axons and dendrites.
Dendritic spines change shape.
Unique extracellular proteins are deposited at synapses in-
volved in long-term memory.