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(cf. synaptic strength) can also be regulated. In the
adult nervous system, the strength of synaptic trans-
mission changes dramatically with use, and these
alterations support the storage of memories (see BOX:
Remaining Flexible). The first studies to draw a strong
causal relationship between environmental stimula-
tion and the development of connections were per-
formed in the cat visual system (Wiesel and Hubel,
1963, 1965; Hubel and Wiesel, 1965). In control animals,
extracellular recordings from cortex show that most
neurons fire action potentials in response to stimula-
tion of both eyes. However, when visual stimulation to
one eye is decreased during development, there is a
dramatic loss in the ability of that eye to activate cor-
tical neurons. The result suggests that synapses driven
by the closed eye were either eliminated or weakened.
Even though the initial connectivity of the visual
pathway is quite accurate (Chapter 6), it is apparently
not stable. Synaptic connections can be altered perma-
nently by a developmental mechanism that makes use
of electrical activity.
What is the evidence that synapses are eliminated
in the developing nervous system? How widespread
is this mechanism? Two experimental approaches have
been taken to determine whether a loss of synapses
occurs during development. First, intracellular record-
ings show changes in the number of functional affer-
ents per postsynaptic neuron. Second, anatomical
studies reveal that single axonal arbors become spa-
tially restricted within the target population. But how
do these detailed synaptic decision impact on nervous
system performance? To answer this question, we will
shift our attention from the molecular level to experi-
ments that explore nervous system function and behav-
ioral performance. One way to examine whether all of
the synapses are working together correctly is to study
the response of single neurons to sensory stimuli, such
as light or sound. Many auditory neurons respond
with great accuracy to the location of a sound source in
space, and this reflects both the number and strength
of its synaptic inputs. If there are immature patterns of
connectivity, then one might expect that auditory
neurons will respond to an unusually broad range of
spatial stimuli. Therefore, a neuron's computational
abilities are a sensitive assay of synaptic refinement.
by merely looking at neonatal and adult tissue sections
under the microscope. Instead, quantitative compar-
isons must be made using measurements from many
neurons. How is it possible to count the number of
afferents per postsynaptic neuron? An imaginative
approach to this problem, first employed in the early
1970s, used intracellular recordings and electrical stim-
ulation of the afferent pathway. The basic assumptions
are that each axon will evoke a postsynaptic potential
(PSP) when stimulated, and that the PSPs will
summate linearly, in discrete steps, as each additional
fibers is recruited by the electric stimulus (Figure 9.2).
Therefore, the increments in PSP size provide an esti-
mate of the number of axons making a functional
contact on a single muscle fiber or neuron.
When this experiment was performed at the mature
neuromuscular junction, a single large PSP was
recorded, indicating that the muscle fiber was inner-
vated by a single motor nerve terminal. However,
when the same experiment was performed in neona-
tal animals, the PSP size first doubled and then tripled
in amplitude as the stimulus activated two, then three,
motor axons (Figure 9.3). Similar observations have
been made in developing chick, rat, and kitten muscle
(Redfern, 1970; Bagust et al., 1973; Bennett and
Pettigrew, 1974). The elimination of convergent motor
axons at the rat soleus muscle results in a decrease
Stimulate one afferent
Record Postsynaptic Potentials
Stimulate two afferents
Stimulate three afferents
FIGURE 9.2 An electrophysiological method for determining the
number of inputs converging onto a neuron. A stimulating electrode
is placed on the afferent population while an intracellular recording
is obtained from the postsynaptic cell. As the stimulation current is
increased, the afferent inputs are recruited to become active. When
a single afferent is active (top), the postsynaptic potential (PSP) is
small. When two (middle), and then three afferents are activated
(bottom), the PSP become quantally larger. One can estimate the
number of inputs by counting the number of quantal increases in
PSP amplitude, in this case three.
The developmental loss of synaptic contacts has
been observed throughout the nervous system, from
the nerve-muscle junction of invertebrates to the cere-
bral cortex of primates. These changes are not obvious
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