CHAPTER 6
Synaptic & Junctional Transmission 119CLINICAL 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 ofacetylcholine 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
interneuronSpinal
cordExtensor
motor
neuronCurrent passing
Recording
Extracellular Recording
stimulating
electrodes
Ia afferent fibers
from muscle
spindles of
quadricepsSensory neuron
Extensor
motor neuronSensory
neuron
Muscle
spindleAStretch reflex circuit for knee jerkBExperimental setup for recording from cells in the circuitIPSP
Motor neuron
InterneuronMotor neuron
Sensory neuronEPSPRecording Current passingEPSPEPSPIPSPIa afferent fibers
from muscle
spindles of
quadricepsInhibitory
interneurons
Flexor
motor
neuronRecordingFlexor
motor
neuron