CHAPTER 6
Synaptic & Junctional Transmission 119
CLINICAL BOX 6–1
Botulinum and Tetanus Toxins
Several deadly toxins which block neurotransmitter release
are zinc endopeptidases that cleave and hence inactivate pro-
teins in the fusion–exocytosis complex.
Tetanus toxin
and
botulinum toxins
B, D, F, and G act on synaptobrevin, and
botulinum toxin C acts on syntaxin. Botulinum toxins A and B
act on SNAP-25. Clinically, tetanus toxin causes spastic paraly-
sis by blocking presynaptic transmitter release in the CNS, and
botulism causes flaccid paralysis by blocking the release of
acetylcholine at the neuromuscular junction. On the positive
side, however, local injection of small doses of botulinum
toxin (botox) has proved effective in the treatment of a wide
variety of conditions characterized by muscle hyperactivity.
Examples include injection into the lower esophageal sphinc-
ter to relieve achalasia and injection into facial muscles to re-
move wrinkles.
FIGURE 6–6
Excitatory and inhibitory synaptic connections mediating the stretch reflex provide an example of typical circuits within the
CNS. A)
The stretch receptor sensory neuron of the quadriceps muscle makes an excitatory connection with the extensor motor neuron of the same muscle
and an inhibitory interneuron projecting to flexor motor neurons supplying the antagonistic hamstring muscle.
B)
Experimental setup to study excitation and
inhibition of the extensor motor neuron. Top panel shows two approaches to elicit an excitatory (depolarizing) postsynaptic potential or EPSP in the extensor
motor neuron–electrical stimulation of the whole Ia afferent nerve using extracellular electrodes and intracellular current passing through an electrode in-
serted into the cell body of a sensory neuron. Bottom panel shows that current passing through an inhibitory interneuron elicits an inhibitory (hyperpolariz-
ing) postsynaptic potential or IPSP in the flexor motor neuron.
(From Kandel ER, Schwartz JH, Jessell TM [editors]:
Principles of Neural Science,
4th ed. McGraw-Hill, 2000.)
Quadriceps
(extensor)
Hamstring
(flexor)
Inhibitory
interneuron
Spinal
cord
Extensor
motor
neuron
Current passing
Recording
Extracellular Recording
stimulating
electrodes
Ia afferent fibers
from muscle
spindles of
quadriceps
Sensory neuron
Extensor
motor neuron
Sensory
neuron
Muscle
spindle
AStretch reflex circuit for knee jerk
BExperimental setup for recording from cells in the circuit
IPSP
Motor neuron
Interneuron
Motor neuron
Sensory neuron
EPSP
Recording Current passing
EPSP
EPSP
IPSP
Ia afferent fibers
from muscle
spindles of
quadriceps
Inhibitory
interneurons
Flexor
motor
neuron
Recording
Flexor
motor
neuron