Time course of repetitive heterosynaptic facilitation in Aplysia californica.

The conditioning effect of a strong priming afferent stimulation of one nerve on the excitatory postsynaptic potential (EPSP) which follows a weaker test stimulus of another nerve was demonstrated in single nerve cells of the abdominal ganglion of Aplysia by Kandel and Tauc z-4. This was termed heterosynaptic facilitation (HSF). The present paper focuses on the exhaustion-recovery cycle of HSF and presents support for the view that some of the test neurons can be exhausted by stimulation of the priming nerve alone. The experiments were conducted in over 50 specimens of Aplysia cal(fornica. Intracellular recordings were made from the giant cell of the right upper quadrant of the visceral ganglion in the usual way with micropipettes. For the test and printing stimulation, a combination of two of the five nerves or connectives of the ganglion were used and the stimulus polarity reversed after each stimulus. I f the preparation was allowed to rest for 15 min between the periods of stimulation and if the single priming periods did not exceed 1 min, HSF could be repeated over 25 times without gross decay. After 5-10 rain, continuous paired stimulation without intervals of rest led to a reversible exhaustion, during which the priming effect on the test response decreased to almost zero. Exhaustion could also be obtained by continuous priming alone, i.e. without stimulating the test nerve. A comparatively strong and frequent priming stimulus continuously applied for 15 rain was able to prevent subsequent HSF completely (Fig. 1). A continuous priming stimulation of submaximal strength, producing excitation of a smaller number of afferent and internuncial fibres, had a different effect. The amplitude of the HSF in this case was initially even larger than the effect of pairing in the fresh preparation or the first test response after a long period of rest, but the duration during which the peak amplitude was maintained was significantly shortened (Fig. 2). The test response increased again as soon as the test stimulation or the priming stimulation or both were temporarily stopped. Exhaustion of the priming unit as an explanation for the exhaustion of the HSF seems to be unlikely for several reasons: (1) Switching the priming stimulation to another 'fresh' nerve did not restore an already exhausted HSF. (2) The priming shock still produced spikes at the recorded neuron. (3) After prolonged priming, the test response finally failed or fell beneath control levels, it appears more probable that test units were fired by collaterals from the priming side and an exhaustive amount of transmitter was consumed. Under the circumstances of long periods of submaximal priming, some of the test terminals apparently escaped being fired and exhausted, but were potentiated instead perhaps under the influence of presynaptic graded events. Since the amplitude of the test response is an indicator of transmitter release 1, it could be assumed that within the terminals of these test units transmitter was mobilized from a prestage into a more active form during the prolonged priming period. This accumulated transmitter would then be fully activated and liberated at once during subsequent paired stimulation, causing a large but short-lived increment of the test response.