ACTIVITY-DEPENDENT DEPRESSION OF MECHANOSENSORY DISCHARGE IN APLYSIA

1. Inhibition of action potential discharge in Aplysia mechanosensory neurons after noxious stimulation has not been described previously. The present studies investigated depressive effects of prolonged noxious stimulation and repetitive intracellular activation on the number and latency of action potentials evoked by test stimuli applied to the tail or the nerve innervating the tail. Action potential discharge was monitored in the somata of mechanonociceptors in the pleural ganglia. 2. Repeated brief pinches delivered at 5-s intervals to a sensory neuron's receptive field on the tail initially caused intense activation (10-25 spikes recorded in the soma) followed by a progressive decrease or ''winddown'' of spike number during subsequent pinches. 3. Repeated application to the tail of noxious shock that caused intense activation of sensory neurons (10-22 spikes during the initial shock) produced progressive winddown of discharge similar to that produced by repeated tail pinch. However, sensory neurons that showed lower activation (1-9 spikes) to the same shock displayed windup of discharge during the 10 shocks. These results suggested that prolonged, intense activation depresses subsequent action potential discharge. 4. Changes in the time required for spikes evoked in the tail to reach the central soma were used as an indicator of changes in the excitability and/or conduction velocity of peripheral branches. Repeated pinch within a sensory neuron's receptive field caused an increase in the latency of discharge elicited by test shocks within the receptive field that lasted greater-than-or-equal-to 10 min. Repetitive intracellular stimulation of the sensory neuron soma caused a similar increase in latency. 5. Repetitive soma activation decreased the number of spikes evoked 10 s later by a test shock in the sensory neuron's receptive field, indicating that spike activity depresses the initiation and/or conduction of spikes in peripheral branches. Surprisingly, repeated pinch to the receptive field caused no significant change in the number of spikes evoked by the same test shock. This difference suggests that tail pinch produces concomitant facilitatory effects that oppose the depressive effects of intense spike activity. 6. Depressive effects of repeated pinch and repetitive soma activation were expressed in the axon between the receptive field and the CNS. Spikes evoked by brief test shocks delivered to the nerve containing the axon of the recorded sensory neuron showed a transient increase in latency (perhaps due to a decrease in conduction velocity) after either procedure. Repeated pinch, but not repetitive soma activation, also caused an increase in spike threshold in the nerve. The increases in latency and threshold were not affected by desheathing the nerve or treating it with glutaraldehyde, indicating that these effects were not due to contractions of the nerve sheath. 7. Although repeated tail pinch did not depress the number of action potentials evoked by tail stimulation, it did depress discharge evoked by stimulating the nerve containing the axons of the tested sensory neurons. This depression appears to involve modulation of spike conduction in regions central to the nerve test site because the depression occurred even when the intensity of the nerve test stimulus was tripled. Tail pinch outside the tested sensory neuron's receptive field had little effect on discharge evoked by nerve stimulation. 8. Repeated stimulation of the test nerve (containing axons of the tested sensory neurons) in the isolated nervous system caused winddown of evoked discharge. Neuromodulators released by stimulation of an ''extrinsic'' nerve lacking axons of the tested sensory neuron did not affect test discharge evoked by stimulation of the sensory neuron's axon. Test discharge was depressed for 15 min after repeated intracellular activation of the sensory neuron soma and greater-than-or-equal-to 20 min after pairing repeated soma activation with extrinsic nerve stimulation. This difference suggests that extrinsic neuromodulators may prolong activity-dependent intrinsic depression of discharge. 9. The duration of activity-dependent depression of discharge in the isolated CNS was shortened from greater-than-or-equal-to 20 min to <5 min by reducing Ca2+ influx. Therefore Ca2+ influx and/or Ca2+-dependent neuromodulator release appear to be important for long-lasting depression of sensory discharge but unnecessary for activity-dependent depression of sensory discharge lasting only 10 s. 10. Depression of discharge produced by repeated soma activation did not require activation of the classical Na+-K+ adenosinetriphosphatase because depression was enhanced rather than reduced by bathing the nervous system with ouabain or cooling it to 5-degrees-C. 11. Noxious stimulation that did not produce activation of the tested sensory neuron rarely produced inhibition of action potential discharge. However, extrinsic inhibition lasting only a few seconds was seen in a small number of preparations. 12. Activity-dependent intrinsic depression of discharge builds up with cumulative spike activity, opposing rapid activity-dependent facilitation of discharge that occurs during brief noxious stimulation. Depression of discharge may contribute to escape behavior by transiently reducing sensitivity near a wound, increasing the threshold of withdrawal responses that interfere with locomotion. Depression of discharge may also have homeostatic functions, protecting the sensory neuron or its postsynaptic targets from potentially deleterious effects of excessive activation.