Home LiteratureArticle Details
PMID: 1924365 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Reversal of synaptic depression by serotonin at Aplysia sensory neuron synapses involves activation of adenylyl cyclase.

Goldsmith BA, Abrams TW

Abstract

Facilitation of the monosynaptic connection between siphon sensory neurons and gill and siphon motor neuron contributes to sensitization and dishabituation of the gill and siphon withdrawal reflex in Aplysia. The facilitatory transmitter serotonin (5-HT) initiates two mechanisms that act in parallel to increase transmitter release from siphon sensory neurons. 5-HT acts, at least partly through cAMP, to broaden the presynaptic action potential. 5-HT also initiates a second process that facilitates depressed sensory neuron synapses by a mechanism independent of changes in action potential duration. Recent experiments indicated that either of two protein kinases, cAMP-dependent protein kinase A and protein kinase C, are capable of effectively activating this second facilitatory mechanism, restoring synaptic transmission in depressed synapses. We have used the adenylyl cyclase inhibitor SQ 22,536 [9-(tetrahydro-2-furyl)adenine or THFA] to explore the contribution of cAMP to the reversal of synaptic depression. THFA effectively inhibited both adenylyl cyclase activity in vitro and known cyclase-mediated effects in intact sensory neurons. THFA also completely blocked facilitation of depressed synapses by 5-HT. These results suggest that adenylyl cyclase plays a critical role in the reversal of synaptic depression that contributes to dishabituation in this system.

MeSH Terms
Adenine/analogs & derivatives,pharmacology Adenylyl Cyclase Inhibitors Adenylyl Cyclases/metabolism Animals Aplysia Enzyme Activation Evoked Potentials/drug effects Ganglia/physiology In Vitro Techniques Kinetics Neurons, Afferent/drug effects,enzymology,physiology Phorbol 12,13-Dibutyrate/pharmacology Serotonin/pharmacology Synapses/drug effects,enzymology,physiology
Chemicals
Adenylyl Cyclase Inhibitors 9-(tetrahydro-2-furyl)-adenine Serotonin Phorbol 12,13-Dibutyrate Adenylyl Cyclases Adenine
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Goldsmith B A
Department of Biology, University of Pennsylvania, Philadelphia 19104.
Abrams T W
References (38)
38 references, click to expand
  1. Cyclic AMP-dependent protein kinase closes the serotonin-sensitive K+ channels of Aplysia sensory neurones in cell-free membrane patches.
    Nature. 1985 Jan 31-Feb 6;313(6001):392-5 PMID: 2578623
  2. Mechanism of calcium current modulation underlying presynaptic facilitation and behavioral sensitization in Aplysia.
    Proc Natl Acad Sci U S A. 1980 Nov;77(11):6912-6 PMID: 6256770
  3. 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):113-8 PMID: 2987761
  4. Structural studies on a family of cAMP-binding proteins in the nervous system of Aplysia.
    J Cell Biol. 1986 Jan;102(1):320-31 PMID: 3941158
  5. A potent synthetic peptide inhibitor of the cAMP-dependent protein kinase.
    J Biol Chem. 1986 Jan 25;261(3):989-92 PMID: 3511044
  6. 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):8794-8 PMID: 2430300
  7. Distribution of cAMP and cAMP-dependent protein kinases in Aplysia sensory neurons.
    J Neurosci. 1987 Jan;7(1):291-301 PMID: 3027275
  8. Protein kinase C contains a pseudosubstrate prototope in its regulatory domain.
    Science. 1987 Dec 18;238(4834):1726-8 PMID: 3686012
  9. Biochemical correlates of short-term sensitization in Aplysia: temporal analysis of adenylate cyclase stimulation in a perfused-membrane preparation.
    Proc Natl Acad Sci U S A. 1987 Dec;84(24):9285-9 PMID: 2892199
  10. Dishabituation and sensitization emerge as separate processes during development in Aplysia.
    J Neurosci. 1988 Jan;8(1):197-211 PMID: 3339408
  11. Parallel processing of short-term memory for sensitization in Aplysia.
    J Neurobiol. 1988 Jun;19(4):297-334 PMID: 3288711
  12. Intracellular injection of cAMP induces a long-term reduction of neuronal K+ currents.
    Science. 1988 Jun 17;240(4859):1664-6 PMID: 2837826
  13. cAMP evokes long-term facilitation in Aplysia sensory neurons that requires new protein synthesis.
    Science. 1988 Jun 17;240(4859):1667-9 PMID: 2454509
  14. The molecular heterogeneity of protein kinase C and its implications for cellular regulation.
    Nature. 1988 Aug 25;334(6184):661-5 PMID: 3045562
  15. Site and mechanism of activation of proton-induced sodium current in chick dorsal root ganglion neurones.
    J Physiol. 1988 Jun;400:159-87 PMID: 2458452
  16. Persistent and transcriptionally-dependent increase in protein phosphorylation in long-term facilitation of Aplysia sensory neurons.
    Nature. 1989 May 4;339(6219):51-4 PMID: 2469963
  17. Serotonergic modulation of two potassium currents in the pleural sensory neurons of Aplysia.
    J Neurophysiol. 1989 Sep;62(3):665-79 PMID: 2549212
  18. Depletion of serotonin in the nervous system of Aplysia reduces the behavioral enhancement of gill withdrawal as well as the heterosynaptic facilitation produced by tail shock.
    J Neurosci. 1989 Dec;9(12):4200-13 PMID: 2592997
  19. Identified serotonergic neurons LCB1 and RCB1 in the cerebral ganglia of Aplysia produce presynaptic facilitation of siphon sensory neurons.
    J Neurosci. 1989 Dec;9(12):4227-35 PMID: 2592999
  20. Synaptic plasticity and the modulation of the Ca2+ current.
    J Exp Biol. 1980 Dec;89:117-57 PMID: 6110691
  21. Serotonin and cyclic AMP close single K+ channels in Aplysia sensory neurones.
    Nature. 1982 Sep 30;299(5882):413-7 PMID: 6289122
  22. Serotonin modulates a specific potassium current in the sensory neurons that show presynaptic facilitation in Aplysia.
    Proc Natl Acad Sci U S A. 1982 Sep;79(18):5713-7 PMID: 6957886
  23. Facilitatory transmitter causes a selective and prolonged increase in adenosine 3':5'-monophosphate in sensory neurons mediating the gill and siphon withdrawal reflex in Aplysia.
    J Neurosci. 1982 Dec;2(12):1682-91 PMID: 6292380
  24. Heterosynaptic facilitation and behavioral sensitization are inhibited by lowering endogenous cAMP in Aplysia.
    Brain Res. 1983 Dec 12;288(1-2):95-104 PMID: 6318891
  25. 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):7956-60 PMID: 6096869
  26. Adenylate cyclase system is essential for long-term facilitation at the crayfish neuromuscular junction.
    J Neurosci. 1989 Dec;9(12):4246-52 PMID: 2480401
  27. Sensitizing stimuli cause translocation of protein kinase C in Aplysia sensory neurons.
    Proc Natl Acad Sci U S A. 1990 Mar;87(5):2036-9 PMID: 2155431
  28. Second messengers involved in the two processes of presynaptic facilitation that contribute to sensitization and dishabituation in Aplysia sensory neurons.
    Proc Natl Acad Sci U S A. 1990 Mar;87(5):2040-4 PMID: 2155432
  29. Facilitatory and inhibitory transmitters modulate calcium influx during action potentials in aplysia sensory neurons.
    Neuron. 1990 Oct;5(4):487-99 PMID: 1976321
  30. Selective short- and long-term effects of serotonin, small cardioactive peptide, and tetanic stimulation on sensorimotor synapses of Aplysia in culture.
    J Neurosci. 1990 Oct;10(10):3286-94 PMID: 1698945
  31. Contributions of two types of calcium channels to synaptic transmission and plasticity.
    Science. 1990 Nov 23;250(4984):1142-7 PMID: 2174573
  32. Receptive fields and properties of a new cluster of mechanoreceptor neurons innervating the mantle region and the branchial cavity of the marine mollusk Aplysia californica.
    J Exp Biol. 1991 Mar;156:315-34 PMID: 1675656
  33. Cloning and characterization of Ca(2+)-dependent and Ca(2+)-independent PKCs expressed in Aplysia sensory cells.
    J Neurosci. 1991 Aug;11(8):2303-13 PMID: 1869917
  34. Habituation of the arousal reaction.
    Brain. 1956 Dec;79(4):655-80 PMID: 13396069
  35. Habituation: a model phenomenon for the study of neuronal substrates of behavior.
    Psychol Rev. 1966 Jan;73(1):16-43 PMID: 5324565
  36. Synaptic facilitation and behavioral sensitization in Aplysia: possible role of serotonin and cyclic AMP.
    Science. 1976 Dec 10;194(4270):1178-81 PMID: 186870
  37. Inhibition of adenylate cyclase in human blood platelets by 9-substituted adenine derivatives.
    J Cyclic Nucleotide Res. 1979;5(2):125-34 PMID: 221552
  38. Simulation of synaptic depression, posttetanic potentiation, and presynaptic facilitation of synaptic potentials from sensory neurons mediating gill-withdrawal reflex in Aplysia.
    J Neurophysiol. 1985 Mar;53(3):652-69 PMID: 2580065
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1991-10-15
Pages
9021-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC52643
Subset
IM
Grants
NINDS NIH HHS · NS 25788 · United States
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]