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. 1987 Dec;84(23):8730–8734. doi: 10.1073/pnas.84.23.8730

Tail shock produces inhibition as well as sensitization of the siphon-withdrawal reflex of Aplysia: possible behavioral role for presynaptic inhibition mediated by the peptide Phe-Met-Arg-Phe-NH2.

S L Mackey 1, D L Glanzman 1, S A Small 1, A M Dyke 1, E R Kandel 1, R D Hawkins 1
PMCID: PMC299620  PMID: 3120198

Abstract

Recent studies have shown that, in addition to being modulated by presynaptic facilitation, the sensory neurons of the gill- and siphon-withdrawal reflex of Aplysia are also capable of being modulated by transient presynaptic inhibition produced by the peptide Phe-Met-Arg-Phe-NH2. These two modulatory effects involve different second-messenger systems: the facilitation is mediated through cAMP-dependent protein phosphorylation, and the inhibition is mediated through the lipoxygenase pathway of arachidonic acid. To explore the behavioral function of this inhibition, we have carried out a parametric analysis of the effect of tail shock on the siphon-withdrawal reflex. In addition to producing sensitization of the withdrawal reflex, tail shock also transiently inhibits the reflex. The inhibition is produced by relatively weak shock, whereas sensitization is more prominent and may mask the inhibition with stronger shock. Furthermore, inhibition is not observed after habituation training. Cellular studies suggest that the behavioral inhibition is mediated, at least in part, by presynaptic inhibition of transmitter release from the siphon sensory neurons. Moreover, we have identified an interneuron within the left pleural ganglion (LPL16) that shows Phe-Met-Arg-Phe-NH2 immunoreactivity, is activated by tail shock, and simulates the presynaptic inhibitory actions produced by tail shock. Therefore, our results suggest that presynaptic inhibition mediated by Phe-Met-Arg-Phe-NH2 and its lipoxygenase second messenger contributes to behavioral inhibition of the siphon-withdrawal reflex.

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Selected References

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  1. Abrams T. W. Activity-dependent presynaptic facilitation: an associative mechanism in Aplysia. Cell Mol Neurobiol. 1985 Jun;5(1-2):123–145. doi: 10.1007/BF00711089. [DOI] [PubMed] [Google Scholar]
  2. Abrams T. W., Castellucci V. F., Camardo J. S., Kandel E. R., Lloyd P. E. Two endogenous neuropeptides modulate the gill and siphon withdrawal reflex in Aplysia by presynaptic facilitation involving cAMP-dependent closure of a serotonin-sensitive potassium channel. Proc Natl Acad Sci U S A. 1984 Dec;81(24):7956–7960. doi: 10.1073/pnas.81.24.7956. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Advokat C. Modulation of defensive reflexes in Aplysia californica by appetitive stimulation. Behav Neural Biol. 1980 Mar;28(3):253–265. doi: 10.1016/s0163-1047(80)92259-1. [DOI] [PubMed] [Google Scholar]
  4. Belardetti F., Kandel E. R., Siegelbaum S. A. Neuronal inhibition by the peptide FMRFamide involves opening of S K+ channels. Nature. 1987 Jan 8;325(7000):153–156. doi: 10.1038/325153a0. [DOI] [PubMed] [Google Scholar]
  5. Brezina V., Eckert R., Erxleben C. Suppression of calcium current by an endogenous neuropeptide in neurones of Aplysia californica. J Physiol. 1987 Jul;388:565–595. doi: 10.1113/jphysiol.1987.sp016632. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Brown R. O., Gusman D., Basbaum A. I., Mayeri E. Identification of Aplysia neurons containing immunoreactive FMRFamide. Neuropeptides. 1985 Dec;6(6):517–526. doi: 10.1016/0143-4179(85)90113-1. [DOI] [PubMed] [Google Scholar]
  7. Carew T. J., Hawkins R. D., Kandel E. R. Differential classical conditioning of a defensive withdrawal reflex in Aplysia californica. Science. 1983 Jan 28;219(4583):397–400. doi: 10.1126/science.6681571. [DOI] [PubMed] [Google Scholar]
  8. Carew T. J., Walters E. T., Kandel E. R. Classical conditioning in a simple withdrawal reflex in Aplysia californica. J Neurosci. 1981 Dec;1(12):1426–1437. doi: 10.1523/JNEUROSCI.01-12-01426.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Castellucci V., Kandel E. R. Presynaptic facilitation as a mechanism for behavioral sensitization in Aplysia. Science. 1976 Dec 10;194(4270):1176–1178. doi: 10.1126/science.11560. [DOI] [PubMed] [Google Scholar]
  10. Castellucci V., Pinsker H., Kupfermann I., Kandel E. R. Neuronal mechanisms of habituation and dishabituation of the gill-withdrawal reflex in Aplysia. Science. 1970 Mar 27;167(3926):1745–1748. doi: 10.1126/science.167.3926.1745. [DOI] [PubMed] [Google Scholar]
  11. Dunlap K., Fischbach G. D. Neurotransmitters decrease the calcium conductance activated by depolarization of embryonic chick sensory neurones. J Physiol. 1981 Aug;317:519–535. doi: 10.1113/jphysiol.1981.sp013841. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fredman S. M., Jahan-Parwar B. Intra- and interganglionic synaptic connections in the CNS of Aplysia. Brain Res Bull. 1979 May-Jun;4(3):393–406. doi: 10.1016/s0361-9230(79)80017-9. [DOI] [PubMed] [Google Scholar]
  13. Frost W. N., Castellucci V. F., Hawkins R. D., Kandel E. R. Monosynaptic connections made by the sensory neurons of the gill- and siphon-withdrawal reflex in Aplysia participate in the storage of long-term memory for sensitization. Proc Natl Acad Sci U S A. 1985 Dec;82(23):8266–8269. doi: 10.1073/pnas.82.23.8266. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Goldberg J., Colmers W., Edstrom J., Lukowiak K. Suppression of sensory to motor synaptic transmission and narrowing of the sensory neurone action potential by arginine vasotocin in Aplysia californica. J Exp Biol. 1987 Mar;128:47–62. doi: 10.1242/jeb.128.1.47. [DOI] [PubMed] [Google Scholar]
  15. Hawkins R. D., Abrams T. W., Carew T. J., Kandel E. R. A cellular mechanism of classical conditioning in Aplysia: activity-dependent amplification of presynaptic facilitation. Science. 1983 Jan 28;219(4583):400–405. doi: 10.1126/science.6294833. [DOI] [PubMed] [Google Scholar]
  16. Hawkins R. D., Carew T. J., Kandel E. R. Effects of interstimulus interval and contingency on classical conditioning of the Aplysia siphon withdrawal reflex. J Neurosci. 1986 Jun;6(6):1695–1701. doi: 10.1523/JNEUROSCI.06-06-01695.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hawkins R. D., Castellucci V. F., Kandel E. R. Interneurons involved in mediation and modulation of gill-withdrawal reflex in Aplysia. II. Identified neurons produce heterosynaptic facilitation contributing to behavioral sensitization. J Neurophysiol. 1981 Feb;45(2):315–328. doi: 10.1152/jn.1981.45.2.315. [DOI] [PubMed] [Google Scholar]
  18. Hawkins R. D., Kandel E. R. Is there a cell-biological alphabet for simple forms of learning? Psychol Rev. 1984 Jul;91(3):375–391. [PubMed] [Google Scholar]
  19. Hochner B., Klein M., Schacher S., Kandel E. R. Additional component in the cellular mechanism of presynaptic facilitation contributes to behavioral dishabituation in Aplysia. Proc Natl Acad Sci U S A. 1986 Nov;83(22):8794–8798. doi: 10.1073/pnas.83.22.8794. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Jessell T. M., Iversen L. L. Opiate analgesics inhibit substance P release from rat trigeminal nucleus. Nature. 1977 Aug 11;268(5620):549–551. doi: 10.1038/268549a0. [DOI] [PubMed] [Google Scholar]
  21. Klein M., Kandel E. R. Mechanism of calcium current modulation underlying presynaptic facilitation and behavioral sensitization in Aplysia. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6912–6916. doi: 10.1073/pnas.77.11.6912. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Longley R. D., Longley A. J. Serotonin immunoreactivity of neurons in the gastropod Aplysia californica. J Neurobiol. 1986 Jul;17(4):339–358. doi: 10.1002/neu.480170408. [DOI] [PubMed] [Google Scholar]
  23. Lukowiak K. CNS control over gill reflex behaviors in Aplysia: satiation causes an increase in the suppressive control in older but not young animals. J Neurobiol. 1980 Nov;11(6):591–611. doi: 10.1002/neu.480110609. [DOI] [PubMed] [Google Scholar]
  24. Lukowiak K., Freedman L. The gill withdrawal reflex is suppressed in sexually active Aplysia. Can J Physiol Pharmacol. 1983 Jul;61(7):743–748. doi: 10.1139/y83-115. [DOI] [PubMed] [Google Scholar]
  25. Mudge A. W., Leeman S. E., Fischbach G. D. Enkephalin inhibits release of substance P from sensory neurons in culture and decreases action potential duration. Proc Natl Acad Sci U S A. 1979 Jan;76(1):526–530. doi: 10.1073/pnas.76.1.526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Ocorr K. A., Byrne J. H. Membrane responses and changes in cAMP levels in Aplysia sensory neurons produced by serotonin, tryptamine, FMRFamide and small cardioactive peptideB (SCPB). Neurosci Lett. 1985 Apr 9;55(2):113–118. doi: 10.1016/0304-3940(85)90004-7. [DOI] [PubMed] [Google Scholar]
  27. Pinsker H. M., Hening W. A., Carew T. J., Kandel E. R. Long-term sensitization of a defensive withdrawal reflex in Aplysia. Science. 1973 Dec 7;182(4116):1039–1042. doi: 10.1126/science.182.4116.1039. [DOI] [PubMed] [Google Scholar]
  28. Pinsker H., Kupfermann I., Castellucci V., Kandel E. Habituation and dishabituation of the gill-withdrawal reflex in Aplysia. Science. 1970 Mar 27;167(3926):1740–1742. doi: 10.1126/science.167.3926.1740. [DOI] [PubMed] [Google Scholar]
  29. Piomelli D., Volterra A., Dale N., Siegelbaum S. A., Kandel E. R., Schwartz J. H., Belardetti F. Lipoxygenase metabolites of arachidonic acid as second messengers for presynaptic inhibition of Aplysia sensory cells. Nature. 1987 Jul 2;328(6125):38–43. doi: 10.1038/328038a0. [DOI] [PubMed] [Google Scholar]

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