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Functional roles of peptide cotransmitters at neuromuscular synapses inAplysia

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Abstract

Neuromuscular synapses inAplysia have been used as model systems to study peptidergic cotransmission. Here we describe neuromuscular preparations in which it has been possible to investigate the physiological consequences of peptide transmitter release in detail. In the first preparation, the release of peptide cotransmitters from identified motor neuron B15 has been shown to be sensitive to the pattern of stimulation. High frequencies and long burst durations evoke peptide release that modulates muscle contractions in a manner similar to that produced by exogenous cotransmitter. By contrast, the release of the same peptide transmitters from motor neuron B1 show little dependence on pattern. We conclude that there are no stimulation patterns that are prerequisites for peptide release. Peptide cotransmitter release from motor neuron B47 has also been studied. B47, depending on the stimulation pattern, uses either ACh, which acts as a conventional inhibitory transmitter, or Ach plus neuropeptides, which act as excitatory modulatory cotransmitters. Thus, neuropeptide cotransmitters have the capability to greatly increase synaptic plasticity at neuromuscular synapses.

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References

  • Alevizos A., Karagogeos D., Weiss K. R., Buck L., and Koester J. (1991) R15α1 and R15β2 peptides fromAplysia: comparison of bioactivity, distribution, and function of two peptides generated by alternative splicing.J. Neurobiol. 22, 405–417.

    Article  PubMed  CAS  Google Scholar 

  • Arch S. and Berry R. W. (1989) Molecular and cellular regulation of neuropeptide expression: the bag cell model system.Brain Res. Rev. 14, 181–201.

    Article  PubMed  CAS  Google Scholar 

  • Bartfai T., Iverfeldt K., Fisone G., and Serfozo P. (1988) Regulation of the release of coexisting transmitters.Ann. Rev. Pharmacol. Toxicol. 28, 285–310.

    Article  CAS  Google Scholar 

  • Brezina V., Cropper E. C., Evans C. G., Kupfermann I., and Weiss K. R. (1992) Enhancement of Ca and K currents by modulatory peptide cotransmitters correlated with potentiation and depression of contractions of the ARC muscle ofAplysia.Soc. Neurosci. Abstr. 18, 586.

    Google Scholar 

  • Calabrese R. L. (1989) Modulation of muscle and neuromuscular junctions in invertebrates.Sem. Neurosci. 1, 25–34.

    Google Scholar 

  • Cazalis M., Dayanthi G., and Nordmann J. J. (1985) The role of patterned burst and interburst interval on the excitation-coupling mechanism in the isolated rat neural lobe.J. Physiol. (Lond.) 369, 45–60.

    CAS  Google Scholar 

  • Ch'ng, J. L., Christofides N. D., Anand P., Gibson S. J., Allen Y. S., Su H. C., Tatemoto K., Morrison J. F. B., Polak J. M., and Bloom S. R. (1985) Distribution of galanin immunoreactivity in the central nervous system and the responses of galanin-containing neuronal pathways to injury.Neuroscience 16, 343–354.

    Article  PubMed  Google Scholar 

  • Church P. J. and Lloyd P. E. (1991) Expression of diverse neuropeptide cotransmitters by identified motor neurons inAplysia.J. Neurosci. 11, 618–625.

    PubMed  CAS  Google Scholar 

  • Church P. J., Whim M. D., and Lloyd P. E. (1993) Modulation of neuromuscular transmission by conventional and peptide transmitters released from excitatory and inhibitory motor neurons inAplysia.J. Neurosci. 13, 2790–2800.

    PubMed  CAS  Google Scholar 

  • Church P. J. and Lloyd P. E. (1993) Multiple intracellular recordings from identified neurons in Aplysia during evoked feeding-like activity.Soc. Neurosci. Abstr. 19, 1701.

    Google Scholar 

  • Cohen J. L., Weiss K. R., and Kupfermann I. (1978) Motor control of buccal muscles inAplysia.J. Neurophysiol. 41, 157–180.

    Article  PubMed  CAS  Google Scholar 

  • Cropper E. C., Lloyd P. E., Reed W., Tenenbaum R., Kupfermann I., and Weiss K. R. (1987a) Multiple neuropeptides in cholinergic motor neurons ofAplysia: evidence for modulation intrinsic to the motor circuit.Proc. Natl. Acad. Sci. USA 84, 3486–3490.

    Article  PubMed  CAS  Google Scholar 

  • Cropper E. C., Tenenbaum R., Gawinowicz Kolks M. A., Kupfermann I., and Weiss K. R. (1987b) Myomodulin: a bioactive neuropeptide present in an identified cholinergic buccal motor neuron ofAplysia.Proc. Natl. Acad. Sci. USA 84, 5483–5486.

    Article  PubMed  CAS  Google Scholar 

  • Cropper E. C., Miller M. W., Tenenbaum R., Gawinowicz Kolks M. A., Kupfermann I., and Weiss K. R. (1988) Structure and action of buccalin: a modulatory neuropeptide localized to an identified small cardioactive peptide-containing cholinergic motor neuron ofAplysia californica.Proc. Natl. Acad. Sci. USA 85, 6177–6181.

    Article  PubMed  CAS  Google Scholar 

  • Cropper E. C., Kupfermann I., and Weiss K. R. (1990a) Differential firing patterns of the peptide-containing cholinergic motor neurons B15 and B16 during feeding behavior inAplysia.Brain Res. 522, 176–179.

    Article  PubMed  CAS  Google Scholar 

  • Cropper E. C., Price D., Tenenbaum R., Kupfermann I., and Weiss K. R. (1990b) Release of peptide cotransmitters from a cholinergic motor neuron under physiological conditions.Proc. Natl. Acad. Sci. USA 87, 933–937.

    Article  PubMed  CAS  Google Scholar 

  • Cropper E. C., Vilim F., Vitek A., Miller M. W., Kupfermann I., and Weiss K. R. (1991) RFa peptides are present in the ARC neuromuscular system ofAplysia.Soc. Neurosci. Abstr. 17, 1305.

    Google Scholar 

  • Dale N. and Kandel E. R. (1990) Facilitatory and inhibitory transmitters modulate spontaneous transmitter release at culturedAplysia sensorimotor synapses.J. Physiol. (Lond.) 421, 203–222.

    CAS  Google Scholar 

  • DeCamilli P. and Jahn R. (1990) Pathways to regulated exocytosis in neurons.Ann. Rev. Physiol. 52, 625–645.

    Article  CAS  Google Scholar 

  • Dutton D. and Dyball R. E. J. (1979) Phasic firing enhances vasopressin release from the rat neuro-hypophysis.J. Physiol. (Lond.) 290, 433–440.

    CAS  Google Scholar 

  • Fisher J. M., Sossin W., Newcomb R., and Scheller R. H. (1988) Multiple neuropeptides derived from a common precursor are differentially packaged and transported.Cell 54, 813–822.

    Article  PubMed  CAS  Google Scholar 

  • Fox L. E. and Lloyd P. E. (1993) Evidence that L-glutamate is the excitatory transmitter to buccal muscle I3 inAplysia.Soc. Neurosci. Abstr. 19, 490.

    Google Scholar 

  • Gibson S. J., Polak J. M., Bloom S. R., Sabate I. M., Muldberry P. M., Ghatel M. A., McGrego G. P., Morrison J. F. B., Kelly J. S., Evans R. M., and Rosenfeld M. G. (1984) Calcitonin gene-related peptide immunoreactivity in the spinal cord of man and eight other species.J. Neurosci. 4, 3101–3111.

    PubMed  CAS  Google Scholar 

  • Hall Z. W. and Sanes J. R. (1993) Synaptic structure and development: the neuromuscular junction.Neuron 10, 99–121.

    Article  Google Scholar 

  • Holz G. G., IV, Kream R. M., Spiegel A., and Dunlap K. (1989) G proteins couple α-adrenergic and GABAb receptors to inhibition of peptide secretion from peripheral sensory neurons.J. Neurosci. 9, 657–666.

    PubMed  CAS  Google Scholar 

  • Hooper S. L., Cropper E. C., Probst W. C., Kupfermann I., and Weiss K. R. (1992) Effects of neuron B16 stimulation and myomodulin application on cAMP and PKA levels in ARC muscle ofAplysia.Soc. Neurosci. Abstr. 18, 1105.

    Google Scholar 

  • Jan Y. N. and Jan L. Y. (1983) A LHRH-like peptidergic neurotransmitter capable of ‘action at a distance’ in autonomic ganglia.Trends Neurosci. 6, 320–325.

    Article  Google Scholar 

  • Kow L.-M. and Pfaff D. W. (1988) Neuromodulatory actions of peptides.Ann. Rev. Pharmacol. Toxicol. 28, 163–168.

    Article  CAS  Google Scholar 

  • Kuhlman, J. R., Li C., and Calabrese R. L. (1985) FMRF-amide-like substances in the Leech. I. Immunocytological localization.J. Neurosci. 5, 2301–2309.

    PubMed  CAS  Google Scholar 

  • Kupfermann I. (1991) Functional studies of cotransmission.Physiol. Rev. 71, 683–731.

    PubMed  CAS  Google Scholar 

  • Laufer R. and Changeux J.-P. (1989) Calcitonin generelated peptide and cyclic AMP stimulate phosphoinositide turnover in skeletal muscle cells.J. Biol. Chem. 264, 2683–2689.

    PubMed  CAS  Google Scholar 

  • Lloyd P. E. (1988) Fast axonal transport of modulatory neuropeptides from central ganglia to components of the feeding system inAplysia.J. Neurosci. 8, 3507–3514.

    PubMed  CAS  Google Scholar 

  • Lloyd P. E., Kupfermann I., and Weiss K. R. (1984) Evidence for parallel actions of a molluscan neuropeptide and serotonin in mediating arousal inAplysia.Proc. Natl. Acad. USA 81, 2934–2937.

    Article  CAS  Google Scholar 

  • Lloyd P. E., Mahon A. C., Kupfermann I., Cohen J. L., Scheller R. H., and Weiss K. R. (1985) Biochemical and immunocytological localization of molluscan small cardioactive peptides (SCPs) in the nervous system ofAplysia californica.J. Neurosci. 5, 1851–1861.

    PubMed  CAS  Google Scholar 

  • Lloyd P. E., Frankfurt M., Stevens P., Kupfermann I., and Weiss K. R. (1987a) Biochemical and immunocytological localization of the neuropeptides cytological localization of the neuropeptides FMRFamide, SCPA, and SCPB, to neurons involved in the regulation of feeding inAplysia.J. Neurosci. 7, 1123–1132.

    PubMed  CAS  Google Scholar 

  • Lloyd P. E., Kupfermann I., and Weiss K. R. (1987b) The sequence of small cardioactive peptide A: a second member of a class of neuropeptides inAplysia.Peptides 8, 179–184.

    Article  PubMed  CAS  Google Scholar 

  • Lloyd P. E., Kupfermann I., and Weiss K. R. (1988) Central peptidergic neurons regulate gut motility inAplysia.J. Neurophysiol. 59, 1613–1626.

    PubMed  CAS  Google Scholar 

  • Lopez V., Wickham L., and Desgroseillers L. (1993) Molecular cloning of myomodulin cDNA, a neuropeptide precursor gene expressed in neuron L10 ofAplysia californica.DNA Cell Biol. 12, 53–61.

    Article  PubMed  CAS  Google Scholar 

  • Lotshaw D. P. and Lloyd P. E. (1990) Peptidergic and serotonergic facilitation of a neuromuscular synapse inAplysia.Brain Res. 526, 81–94.

    Article  PubMed  CAS  Google Scholar 

  • Mahon A. C., Lloyd P. E., Weiss K. R., Kupfermann I., and Scheller R. H. (1985) The small cardioactive peptides A and B ofAplysia are derived from a common precursor molecule.Proc. Natl. Acad. Sci. USA 82, 3925–3929.

    Article  PubMed  CAS  Google Scholar 

  • Mayeri E., Rothman B. S., Brownell P. H., Branton W. D., and Padgett L. (1985) Nonsynaptic characteristics of neurotransmission mediated by egglaying hormone in the abdominal ganglion ofAplysia.J. Neurosci. 5 2060–2077.

    PubMed  CAS  Google Scholar 

  • Miller M. W., Cropper E. C., Eisinger K., Vilim F., Tenenbaum R., Beushausen S., Brosius J., Kupfermann I., and Weiss K. R. (1989) The buccalin neuropeptide family inAplysia: purification of buccalin C and sequence of additional peptides predicted by a cDNA clone.Soc. Neurosci. Abstr. 15, 665.

    Google Scholar 

  • Miller M. W., Alevizos A., Cropper E. C., Vilim F., Karagogeos D., Kupfermann I., and Weiss K. R. (1991a) Localization of myomodulin-like immuno-reactivity in the central nervous system and peripheral tissues ofAplysia californica.J. Comp. Neurol. 314, 627–641.

    Article  PubMed  CAS  Google Scholar 

  • Miller M. W., Stamm S., Cropper E. C., Vilim F., Beushausen S., Brosius J., Kupfermann I., and Weiss K. R. (1991b) Characterization of a cDNA clone encoding multiple myomodulin-related neuropeptides inAplysia.Soc. Neurosci. Abstr. 17, 1305.

    Google Scholar 

  • Miller M. W., Alevizos A., Cropper E. C., Kupfermann I., and Weiss K. R. (1992) Distribution of buccalinlike immunoreactivity in the central nervous system and peripheral tissues ofAplysia californica.J. Comp. Neurol. 320, 182–195.

    Article  PubMed  CAS  Google Scholar 

  • Morris, H. R., Panico M., Karplus A., Lloyd P. E., and Riniker B. (1982) Elucidation by FAB-MS of the structure of a new cardioactive peptide fromAplysia.Nature 300, 643–645.

    Article  PubMed  CAS  Google Scholar 

  • Morton D. W. and Chiel H. J. (1993)In vivo buccal nerve activity that distinguishes ingestion from rejection can be used to predict behavioral transitions inAplysia.J. Comp. Physiol. A. 172, 17–32.

    Article  PubMed  CAS  Google Scholar 

  • Mudge A., Leeman S. E., and Fischbach G. D. (1979) Enkephalin inhibits release of substance P from sensory neurons in culture and decreases action potential duration.Proc. Natl. Acad. Sci. USA 76, 526–530.

    Article  PubMed  CAS  Google Scholar 

  • Mulle C., Benoit P., Pinset C., Roa M., and Changeux J.-P. (1988) Calcitonin gene-related peptide enhances the rate of desensitization of the nicotinic acetylcholine receptor in cultured mouse muscle cells.Proc. Natl. Acad. Sci. USA 85, 5728–5732.

    Article  PubMed  CAS  Google Scholar 

  • Ohhashi T. and Jacobowitz D. M. (1988) Effects of calcitonin gene-related peptide on neuromuscular transmission in the isolated rat diaphragm.Peptides 9, 613–617.

    Article  PubMed  CAS  Google Scholar 

  • O'Shea M., Bishop C. A. (1982) Neuropeptide proctolin associated with an identified skeletal motoneuron.J. Neurosci. 4, 521–529.

    Google Scholar 

  • Peng Y. and Horn J. P. (1991) Continuous repetitive stimuli are more effective than bursts for evoking LHRH release in bullfrog sympathetic ganglia.J. Neurosci. 11, 85–95.

    PubMed  CAS  Google Scholar 

  • Price D. A. and Greenberg M. J. (1977) Structure of a molluscan cardioexcitatory neuropeptide.Science 197, 670,671.

    Article  PubMed  CAS  Google Scholar 

  • Probst W. C., Cropper E. C., Hooper S. L., Kupfermann I., and Weiss K. R. (1992) Convergent peptidergic phosphorylation of proteins in the ARC muscle ofAplysia Soc.Neurosci. Abstr. 18, 1104.

    Google Scholar 

  • Rosen S. C., Teyke T., Miller M. W., Weiss K. R., and Kupfermann I. (1991) Identification and characterization of cerebral-to-buccal interneurons implicated in the control of motor programs associated with feeding inAplysia.J. Neurosci. 11, 3630–3655.

    PubMed  CAS  Google Scholar 

  • Schwarz T. L., Lee G. M. H., Siwicki K. K., Standaert D. G., and Kravitz E. A. (1984) Proctolin in the lobster: the distribution, release, and characterization of a likely neurohormone.J. Neurosci. 4, 1300–1311.

    PubMed  CAS  Google Scholar 

  • Simmons L. K., Schuetze S. M., and Role L. W. (1990) Substance P modulates single-channel properties of neuronal nicotinic acetylcholine receptors.Neuron 2, 393–403.

    Article  Google Scholar 

  • Sossin W. S., Sweet C. A., and Scheller R. H. (1990) Dale's hypothesis revisited: different neuropeptides derived from a common prohormone are targeted to different processes.Proc. Natl. Acad. Sci. USA 87, 4845–4848.

    Article  PubMed  CAS  Google Scholar 

  • Taussig, R., Kaldany R.-R., Rothbard J. B., Schoolnik G., and Scheller R. H. (1985) Expression of the L11 neuropeptide gene in theAplysia central nervous system.J. Comp. Neurol. 238, 53–64.

    Article  PubMed  CAS  Google Scholar 

  • Vilim F. S., Kupfermann I., and Weiss K. R. (1990) Ultrastructural localization of SCP and buccalin-like immunoreactivity in the accessory radula closer muscle ofAplysia.Soc. Neurosci. Abstr. 16, 306.

    Google Scholar 

  • Vilim F. S., Price D. A., Lesser W., Kupfermann I., and Weiss K. R. (1991) Direct measurement of peptide co-transmitter release following intracellular stimulation of a single identified motor neuron inAplysia.Soc. Neurosci. Abstr. 17, 1305.

    Google Scholar 

  • Weiss K. R., Cohen J. L., and Kupfermann I. (1978) Modulatory control of buccal musculature by a serotonergic neuron (metacerebral cell) inAplysia.J. Neurophysiol. 41, 181–203.

    PubMed  CAS  Google Scholar 

  • Weiss K. R., Mandelbaum D. E., Schonberg M., and Kupfermann I. (1979) Modulation of buccal muscle contractility by serotonergic metacerebral cells inAplysia: evidence for a role of cyclic adenosine monophosphate.J. Neurophysiol. 42, 791–803.

    PubMed  CAS  Google Scholar 

  • Weiss K. R., Lloyd P. E., Cropper E. C., Frankfurt M., and Kupfermann I. (1986) FMRF-amide is present in the ARC muscle ofAplysia and depresses its contractions.Soc. Neurosci. Abstr. 12, 947.

    Google Scholar 

  • Weiss K. R., Brezina V., Cropper E. C., Hooper S. L., Miller M. W., Probst W. C., Vilim F. S., and Kupfermann I. (1992) Peptidergic co-transmission inAplysia: functional implications for rhythmic behaviors.Experientia 48, 456–463.

    Article  PubMed  CAS  Google Scholar 

  • Whim M. D. and Lloyd P. E. (1989) Frequency-dependent release of peptide cotransmitters from identified cholinergic motor neurons inAplysia.Proc. Natl. Acad. Sci. USA 86, 9034–9038.

    Article  PubMed  CAS  Google Scholar 

  • Whim M. D. and Lloyd P. E. (1990) Neuropeptide cotransmitters released from an identified cholinergic motor neuron modulate neuromuscular efficacy inAplysia.J. Neurosci. 10, 3313–3322.

    PubMed  CAS  Google Scholar 

  • Whim M. D. and Lloyd P. E. (1992) Modulation of peptide release from single identifiedAplysia neurons in culture.J. Neurosci. 12, 3545–3553.

    PubMed  CAS  Google Scholar 

  • Whim M. D. and Lloyd P. E. (1993) Parameters which determine the release of peptide cotransmitters (SCPs) vary betweenAplysia motor neurons.Soc. Neurosci. Abstr. 19, 30.

    Google Scholar 

  • Willard A. (1990) A vasoactive intestinal peptide-like cotransmitter at cholinergic synapses between rat myenteric neurons in cell culture.J. Neurosci. 10, 1025–1034.

    PubMed  CAS  Google Scholar 

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Whim, M.D., Church, P.J. & Lloyd, P.E. Functional roles of peptide cotransmitters at neuromuscular synapses inAplysia . Mol Neurobiol 7, 335–347 (1993). https://doi.org/10.1007/BF02769181

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