Physiological and morphological effects of post-ganglionic axotomy on presynaptic nerve terminals.

1. Electrophysiological and electron microscope studies were done on cells in the ciliary ganglion of chickens which had been axotomized on the day of hatching. 2. By the third day after post-ganglionic axotomy both electrical and chemical transmission through the ganglion were severely depressed; by the fifth day ganglionic transmission had disappeared. 3. Action potential initiation and conduction in axotomized cells and in their associated presynaptic nerve terminals were unimpaired 3-4 days after axotomy. 4. Depression of ganglionic transmission in 3-4 day axotomized preparations was due to a reduction in amplitude of both the excitatory post-synaptic potential (e.p.s.p.) and the electrical coupling potential in individual ganglion cells. 5. In addition to being reduced in amplitude, e.p.s.p.s in axotomized cells were more subject to fatigue during low frequency (1/sec) stimulation. 6. The reduction in e.p.s.p. amplitude was due to a reduction in both the mean quantal content of the e.p.s.p.s and the calculated depolarization produced by an individual quantum of transmitter. On the average the e.p.s.p. was reduced by a factor of about 4, the mean quantum content to about two thirds normal and the quantal size to about a third normal, compared with responses in unaxotomized cells of the same age. 7. Ultrastructural studies revealed a progressive maturation of pre-synaptic terminals in normal ganglia between 0 and 9 days after hatching. Over this period the content of synaptic vesicles and mitochondria in the terminals increased and the background matrix became more dense. 8. After axotomy these signs of maturation was abolished or reversed, particularly from the third day onward. In addition there was an increase in the number of cell sections in which no synaptic terminals were observed. 9. It was concluded that loss of synaptic transmission was due to at least three factors: a reduction in release of transmitter from presynaptic terminals, a reduction in quantal size, probably due to a loss of post-synaptic sensitivity, and a partial loss of presynaptic contact.