Reduction of quantum contents of synaptic potentials after postsynaptic axotomy.
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Biomedical subjects
Publications and source records attributed to H R Brenner.
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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.
1. Isolated cell clusters from ciliary ganglia of 3- to 4-day-old chickens were used to examine the electrical characteristics and sensitivity to iontophoretically applied acetylcholine (ACh) of normal cells and cells that had been axotomized on the day of hatching. 2. Resting potentials, input resistances and capacitances were the same in axotomized cells as in normal cells. These averaged about 70 mV, 165 Momega and 35 pF respectively. 3. Sensitivity to iontophoretically applied ACh was lower in axotomized cells than in normal cells by a factor of about 8. The rise times of the ACh potentials were the same in the two groups; indicating that the reduced sensitivity was not due to a diffusion barrier. 4. The slopes of the dose-reponse curves, plotted on a double-logarithmic scale, suggested that the co-operative action of two ACh molecules was involved in activating a post-synaptic conductance channel. This relation was unaltered by axotomy. 5. The estimated reversal potential for the action of ACh was unchanged after axotomy. 6. Cells in isolated clusters were similar to those in intact ganlia with respect to threshold depolarization, amplitude and time course of action potentials and ability to generate repetitive action potentials. There were no differences in these characteristics between normal and axotomized cells. 7. Cells in the isolated clusters had input resistances which were larger by a factor of 2-3 and capacitances that were smaller by a factor of about 2 than those of cells in intact ganglia. It is suggested that these differences were due to loss of initial segments of axons from the isolated cells. 8. Normal cells in the isolated clusters displayed spontaneous miniature synaptic potentials, indicating that synaptic integrity was maintained during the isolation procedure. As in intact ganglia, no spontaneous activity was observed in axotomized cells.
Spontaneous and evoked release of transmitter at neuromuscular junctions in three different leg muscles of a tarantula (Dugesiella hentzi) was investigated. In most cases the spontaneous miniature potentials were released independently, although bursts from single synaptic junctions occasionally occurred. In contrast to recent findings in other arthropod muscles, focal extracellular recording from junctional areas revealed that the evoked release of transmitter quanta followed Poisson's theorem at low quantal content synaptic junctions in arachnid muscles.
The formation of a motor endplate is characterized by a complex series of changes in the properties of the subsynaptic acetylcholine receptors (AChRs). Among the last changes to occur are the shortening of the apparent mean open time of their ion channels from about 4 to 1 ms and an increase in the single-channel conductance. This conversion of channel gating at the endplate seems to be induced by the motor neurone. We report here that fast channel gating also develops at nerve-free endplate sites of fibres that had been denervated while gating was still slow. At such sites, junctional folds will develop in the absence of the nerve terminal. Although the conversion of channel gating and the formation of junctional folds are late events in endplate development, the neural signals inducing these changes must therefore act at the earliest stages of junctional development.
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