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Stimulate
1
2
2
1
2
Neuron 1
2 nA
20 ms
stim 2
Muscle
6
Neuron 2
Neuron 1
Neuron 2
0
0
20
40
Time (min)
B
Loss of AChRs under unstimulated synapse
Before stimulation
After stimulation
C
Model
Active
terminal
Inactive
terminal
P
P
PKC
P
P
PKA
FIGURE 9.25 Heterosynaptic depression at the neuron-muscle synapse in vitro. A. Whole-cell recordings
were made from Xenopus muscle cells that were co-innervated by two neurons (left). Evoked synaptic cur-
rents (ESCs) were measured in response to stimulation of each neuron. A strong stimulus was then applied
to neuron 2 (red), and the strength of each neuron was tested again. This procedure leads to smaller evoked
synaptic currents from the unstimulated neuron (green) but no change to neuron 2 (top right). The graph of
ESC amplitude before and after stimulation of neuron 2 shows that the depression is long-lasting (bottom
right). B. Heterosynaptic depression is associated with a loss of postsynaptic AChRs. Muscle cells are co-
innervated by two neurons in vitro, as above. When one neuron is stimulated for 1-2 hours, the nonstimu-
lated neuron displays heterosynaptic depression and a loss of AChRs beneath its synapse. The images show
staining for nerve (green) and AChR clusters (red) beneath the unstimulated synapse before (left) and after
(right) heterosynaptic depression. AChR aggregates are stained with rhodamine-bungarotoxin. C. Model of
activity-dependent synapse elimination. The active terminal increases PKA and PKC locally. PKC phospho-
rylates AChRs beneath the inactive terminal, leading to their loss. However, PKA activity can protect the
AChRs beneath the active terminal. PKC may become activated by calcium influx, whereas PKA may become
activated by a ligand that is released along with ACh. (From Lo and Poo, 1992; Li et al., 2001; Nelson et al.,
2003)
 
 
 
 
 
 
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