SUMMARY1. Intracellular records from post-ganglionic neurones of the rat superior cervical ganglion revealed two non-synaptic potentials dependent upon Ca2+, a hyperpolarizing afterpotential (h.a.p.) and a tetrodotoxin (TTX)-insensitive spike.2. The h.a.p. followed regenerative discharge of the membrane potential in normal and TTX-containing Locke solution.3. The h.a.p. appeared to arise from an increased K+ conductance because it was associated with a decrease in input resistance, reversed at -90 mV, and was proportional in magnitude to the extracellular K+ concentration.4. Tetraethylammonium (TEA) and 4-aminopyridine (4-AP) apparently antagonized a voltage-sensitive K+ conductance because they broadened the action potential. However, these substances reduced only slightly the peak amplitude and earliest phases of the h.a.p.5. The TTX-insensitive spike was most apparent when TEA was present and was invariably followed by an h.a.p. with a magnitude proportional to that of the spike.6.

SUMMARY1. Brief tetanic stimulation of the preganglionic nerve induced a persistent potentiation ofnicotinic synaptic transmission in the rat superior cervical sympathetic ganglion.2. Quantitative measurements of the post-tetanic increase in synaptic efficacy revealed two distinct time courses. The early, rapidly decaying component, termed post-tetanic potentiation (p.t.p.), had a decay time constant of 2-3 min, as reported elsewhere. The duration of the more persistent component, called long-term potentiation (l.t.p.), was extremely temperature dependent, lasting much longer at 32 0C than at 22 'C. In half of the experiments performed at 32 'C, l.t.p. showed no detectable decay over the course of 1 h or more after a brief tetanic stimulation. Other experiments were conducted at 22 'C.3. The induction of l.t.p. was dependent on the extracellular [Ca2+]. Transient elevation of the extracellular [K+] also produced a long-term enhancement of synaptic efficacy, and this effect was also Ca2+ dependent.4. The tetani that were effective in inducing l.t.p. (5-20 Hz for 5-20 s) were well within the physiological range of preganglionic activity. The magnitude and time course were related to frequency and duration of stimulation.5. The occurrence of l.t.p. was restricted to those preganglionic fibres that were tetanically stimulated. This lack of heterosynaptic or generalized effects was demonstrated by splitting the preganglionic nerve into two branches that could be independently tested and conditioned.6. Physiological activation of muscarinic or nicotinic receptors apparently does not play an essential role in causing ganglionic l.t.p., which is expressed as an enhancement of nicotinic transmission. A muscarinic antagonist (2 /LM-atropine) did not block l.t.p.Preganglionic stimulation induced l.t.p. even when a high concentration of a nicotinic antagonist (3 mM-hexamethonium) was present during the tetanic stimulation.Furthermore, bath application of a cholinergic agonist (100-1000 /M-carbachol) could not substitute for tetanic stimulation in provoking l.t.p.7. Activation of adrenergic receptors also appeared not to play an essential role.Neither a fl-adrenergic antagonist (10 /M-sotolol or 1 /LM-propranolol) nor an aadrenergic antagonist (1 liM-phentolamine) had any significant effect on the magnitude or duration of l.t.p.

SUMMARY1. Post-ganglionic neurones of the rat superior cervical ganglion were studied in vitro (21-26 'C) using single intracellular micro-electrode methods.2. Three Ca2+-dependent potentials were studied: the shoulder on the normal action potential, the hyperpolarizing afterpotential (h.a.p.), and the Ca2+ spike.3. Bath-applied noradrenaline reversibly inhibited these Ca2+-dependent poten- 4. Noradrenaline (10OIM) hyperpolarized most neurones (1-6 mV) studied, with no detectable change in resting membrane conductance.5. Superfusion with low external Ca2+ and high Mg2+ mimicked the effect of noradrenaline. Either procedure alone antagonized the h.a.p. conductance increase but did not alter the h.a.p. reversal potential. However, in the presence of low Ca2+, high Mg2+, the remaining action potential and h.a.p. were not further reduced by noradrenaline.6. The Ca2+-dependent shoulder of the action potential did appear dependent upon GE. Noradrenaline and low Ca2+ antagonized the shoulder when enhanced by TEA+ or Ba +.7. Both the rate of rise and amplitude of the Ca2+ spike were antagonized by noradrenaline.8. We propose that activation of an a-adrenoceptor inhibits a voltage-sensitive Ca2+ conductance (GC&(v)), thereby reducing the inward Ca2+ current which may generate the normal action potential shoulder and the rising phase of the Ca2+ spike.

Synaptic potentials and changes in resting membrane potentials of superior cervical ganglia of the rabbit were measured in the presence of adenosine 3',5'-monophosphate and agents that affect its metabolism. Adenosine 3',5'-monophosphate and its mono- and dibutyryl derivatives caused a hyperpolarization of the postganglionic neurons. Theophylline potentiated the slow inhibitory postsynaptic potential that follows synaptic transmission, as well as the hyperpolarization of postganglionic neurons caused by exogenous dopamine. Conversely, prostaglandin E(1) inhibited both the slow inhibitory postsynaptic potential and the dopamine-induced hyperpolarization. We hypothesize that the slow inhibitory postsynaptic potential as well as the dopamine-induced hyperpolarization result from increased amounts of adenosine 3'5'-monophosphate in the postganglionic neurons. The dibutyryl derivative of guanosine 3'5'-monophosphate caused a depolarization of the postganglionic neurons, which is consistent with the possibility that guanosine 3'5'-monophosphate mediates synaptic transmission at muscarinic cholinergic synapses.

Brief tetanic stimulation of the preganglionic nerves to the superior cervical ganglion enhances the postganglionic response to single preganglionic stimuli for 1 to 3 hours. This long-term potentiation of transmission through the ganglion is apparently not attributable to a persistent muscarinic action of the preganglionic neurotransmitter, acetylcholine, since neither the magnitude nor the time course of the phenomenon is reduced by atropine. The decay of long-term potentiation can be described by a first-order kinetic process with a mean time constant of 80 minutes. We conclude that long-term potentiation, once considered a unique property of the hippocampus, is in fact a more general feature of synaptic function. This form of synaptic memory may significantly influence information processing and control in other regions of the nervous system, including autonomic ganglia.