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inject curare onto
chorioallantoic membrane
A
Ca 2+
Ca 2+
Shell
Ca 2+
Ca 2+
anti-BDNF
Yolk sac
Control
Depolarize (KCI)
Depolarize (KCI)
& anti-BDNF
B
100
20,000
18,000
Curare
16,000
50
14,000
Control
12,000
0
10,000
Control
Depolarize
Depolarize &
anti-BDNF
5
10
15
20
Age (days)
Curare
FIGURE 7.30 Electrical activity enhances the survival of embry-
onic cortex neurons by way of a neurotrophic signal. When the cul-
tures are depolarized by adding KCl to the culture media, calcium
enters the neurons, and the level of BDNF expression increases,
leading to greater neuron survival compared to control media. The
trophic influence of depolarization is eliminated by adding a func-
tion-blocking anti-BDNF antibody to the growth medium. (Adopted
from Ghosh et al., 1994)
FIGURE 7.29 Blocking synaptic transmission prevents normal
motor neuron cell death. A. Neuromuscular transmission can be
blocked by applying curare onto the chorioallantoic membrane of
chick embryos. B. In control animals, over 30% of motor neurons die
after embryonic day 5. When animals are treated with curare from
E6-9, the magnitude of normal cell death is greatly diminished.
(Panel B adopted from Pittman and Oppenheim, 1979)
The activity-dependent expression of BDNF has
been shown to support embryonic cortex neuron sur-
vival in a culture dish (Figure 7.30). BDNF expression
and survival depend on the entry of calcium into the
neurons when they are depolarized in a medium con-
taining a high potassium ion concentration. When
function-blocking antibodies directed against BDNF
are added to these cultures, the trophic effect of depo-
larization is eliminated (Ghosh et al., 1994). Therefore,
neurons may have some influence over the survival
factors that they seek from a target: increased branch-
ing may provide better access, and synaptic transmis-
sion can regulate the amount of factor produced.
Thus, neuron survival may depend on proper access
to the target-derived survival factor rather than on the
total amount of factor produced by the target (Oppen-
heim, 1989). Access could result from a greater number
of synapses. In fact, several observations suggest that
synapse activity and survival factor expression are
entwined with one another. Embryonic hippocampal
neurons grown in dissociated culture for seven days
make numerous synaptic contacts with each other, and
the expression of NGF and BDNF mRNA gradually
increases over this period. This neurotrophin expres-
sion is influenced by synaptic activity: NMDA receptor
blockade decreases neurotrophin expression, whereas
GABA A receptor blockade increases it (Zafra et al.,
1991). Muscle cell expression of the neurotrophin, NT-
4, is also regulated by synaptic activity, and the mor-
phology and function of neuromuscular synapses
depends on this signal (Funakoshi et al., 1995; Bellu-
ardo et al., 2001; Gonzalez et al., 1999). It is possible that
activity-dependent regulation of this neurotrophin
permits motor neuron synapses to obtain access to a
second factor that mediates survival.
AFFERENT REGULATION
OF CELL SURVIVAL
Neuron growth and differentiation occur without
synaptic contacts at first, but maturation and survival
quickly become dependent on neurotransmission and
 
 
 
 
 
 
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