Release of neuropeptides during intracellular stimulation of single identified Aplysia neurons in culture.

Lloyd, Philip E.; Schacher, Samuel; Kupfermann, Irving; Weiss, Klaudiusz R.

doi:10.1073/pnas.83.24.9794

Cited by 32 publications

(45 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…USA 87 (1990) . We characterized firing patterns of neuron B15 during normal feeding behavior and found that when animals made responses to ingest food, neuron B16 fired first, for 0.5-1 sec at [15][16][17][18][19][20] Hz; then the two ARC motor neurons fired together, with neuron B15 firing at half the frequency of neuron B16, i.e., at 7-12 Hz (Fig. 2A).…”

Section: Resultsmentioning

confidence: 99%

Release of peptide cotransmitters from a cholinergic motor neuron under physiological conditions.

Cropper

Price

Tenenbaum

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

In previous studies, we demonstrated that B15, one of the two cholinergic motor neurons of the accessory radula closer muscle ofAplysia, synthesizes two peptides, small cardioactive peptides A and B (SCPA and SCPB), that, when exogenously applied, increase the size and relaxation rate of muscle contractions elicited by motor neuron stimulation. In the present experiments, we obtained evidence that the SCPs are released under physiological conditions. Specifically, we characterized firing patterns of motor neuron B15 during normal behavior, simulated them in vitro, and demonstrated that this type of neuronal activity produces decreases in SCP levels in neuronal processes and terminals. We also obtained evidence that suggests that enough SCP is released under physiological conditions to modulate neuromuscular activity in the accessory radula closer. We demonstrated that physiological activity of neuron B15 produces significant increases in muscle cAMP levels. Furthermore, increases in the size and relaxation rate of muscle contractions can be produced by changes in stimulation parameters that are also likely to maximize effects of released endogenous SCPA and SCPB.In the marine mollusc Aplysia californica, the food arousal state is manifested both as alterations in appetitive feeding behaviors and as increases in the efficiency of consummatory responses (1, 2). Manifestations of arousal in consummatory biting responses are partially produced by modulatory effects of the serotonergic metacerebral cells (MCCs), which have both central and peripheral actions (3)(4)(5). The central actions of the MCCs are exerted on motor neurons utilized in feeding behavior and on the biting central pattern generator. Peripheral effects of the MCCs are exerted directly on the feeding musculature; they increase the size and relaxation rate of muscle contractions elicited by motor neuron stimulation. However, manifestations of arousal in biting responses are not produced exclusively by the MCCs, since effects of arousal can still be partially seen in animals in which the MCCs have been destroyed (5).We have used the accessory radula closer (ARC), an experimentally advantageous muscle, to explore other sources of modulation of the biting musculature. The two cholinergic motor neurons of the ARC synthesize a number of myoactive peptides that are present in fibers and varicosities in the muscle. For example, buccal neuron B15 synthesizes two peptides, small cardioactive peptides A and B (SCPA and SCPB; ref. 6), that, when exogenously applied, exert actions similar to those ofthe MCCs; they increase both the size (7) and relaxation rate (8) of motor neuron-elicited muscle contractions. We have hypothesized that SCPA and SCPB are released as cotransmitters and are at least partially responsible for producing the increase in the efficiency of biting responses that is seen during arousal (6).In the present study, we obtained evidence that the SCPs are released under physiological conditions. Specifically, we recorded B15 synaptic acti...

show abstract

Section: Resultsmentioning

confidence: 99%

Release of peptide cotransmitters from a cholinergic motor neuron under physiological conditions.

Cropper

Price

Tenenbaum

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, it is clear that the stimulation frequencies required to produce peptide release is specified primarily by the properties of the neurons and not the transmitters themselves. For example, release of the SCPs from B15 requires considerably higher firing frequencies than the 2-to 3-Hz stimulation that effectively release the SCPs from B1 and B2 neurons in culture (17).…”

Section: Discussionmentioning

confidence: 99%

“…Immunoreactive fibers and varicosities are present at both central and peripheral sites where the SCPs have been shown to potently modulate the efficacy of synaptic transmission (12,15,16). Finally, the SCPs are released from identified neurons in culture in a stimulation-and calcium-dependent manner (17).…”

Section: Introductionmentioning

confidence: 97%

Frequency-dependent release of peptide cotransmitters from identified cholinergic motor neurons in Aplysia.

Whim

Lloyd

1989

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

145

110

View full text Add to dashboard Cite

We have investigated the release of two peptide cotransmitters from the terminals of a cholinergic motor neuron in Aplysia. Identified motor neuron B15 synthesizes the two small cardioactive peptides (SCP) A and B in addition to acetylcholine. A symmetrical pair of B15 neurons innervate symmetrical buccal muscles, termed 15, which are involved in generating biting movements. The amplitude of I5 contractions is enhanced by the SCPs. Intracellular stimulation of one B15 produces depletion of the SCPs from the stimulated muscle as compared to the unstimulated control muscle. Significant depletion requires either high-frequency stimulation or prolonged bursts at lower frequencies. A second cholinergic motor neuron, B16, also innervates I5 but does not synthesize the SCPs. Stimulation of B16 produced no depletion of the SCPs. Exogenous SCPs potently increase cAMP levels in the muscle. If depletion is a reflection of release, it should be possible to demonstrate an effect ofB15 stimulation on muscle cAMP levels. Indeed, stimulation of B15 did elevate cAMP levels in I5. Stimulation of B16 had no effect on cAMP levels. Increases in cAMP were observed only when B15 was stimulated in a manner that would produce significantly facilitated acetylcholine release. This facilitation could be produced by increased stiniulation frequency, longer burst durations, or shorter interburst intervals. However, B15 is capable of producing cholinergically mediated contractions with stimulation parameters that would not cause release of the SCPs. Thus, B15 appears to function as a purely cholinergic motor neuron when firing slowly, and as a cholinergic/peptidergic neuron when firing rapidly.Over the last decade, it has become clear that many neurons contain multiple transmitters, often one or more peptide transmitters with a single conventional transmitter (1, 2). Knowledge of the regulation of release of coexisting transmitters is crucial to our understanding of the physiological roles of each transmitter and the interactions between them (3-5). The metabolism of conventional transmitters and peptide transmitters differs significantly. Conventional transmitters are synthesized enzymatically at synaptic terminals and, once released, usually have high-affinity uptake systems. Thus, there are cellular mechanisms for maintaining homeostatic levels of conventional transmitters. In contrast, peptide transmitters are cleaved from precursors in the neuronal cell body and transported to remote terminals and there is little evidence for efficient reuptake of most peptides. Consequently, during sustained activation, either the rates of peptide release must be very low compared to total content in the terminals or the peptide content must decline.One class of peptides that have been commonly found to coexist with other transmitters in Aplysia neurons are the small cardioactive peptides (SCPs) (6-8). The SCPs are represented by two peptides, SCPA and SCPB, which are 11 and 9 amino acids in length, respectively. These peptides have similar se...

show abstract

“…The peptides are structurally dissimilar (Lloyd, 1982;Morris et al, 1982;Phares and Lloyd, 1996;Sweedler et al, 2002). Further, they derive from different precursor proteins (Mahon et al, 1985;Vilim et al, 2001;Sweedler et al, 2002). We show that egestive priming during EN stimulation is SCPb-mediated.…”

Section: Discussionmentioning

confidence: 87%

“…Excitability and occlusion experiments were conducted in high divalent ASW, (in mM: 368 NaCl, 10 KCl, 101 MgCl 2 , 13.8 CaCl 2 , and 10 HEPES, pH 7.6; Trudeau and Castellucci, 1992). FCAP (SynPep; Sweedler et al, 2002), CP2 (SynPep;Phares and Lloyd, 1996;Vilim et al, 2001), and SCPb (Lloyd et al, 1986; Anaspec) were superfused at 10 Ϫ6 M, a concentration that produces maximum effects (Koh et al, 2003). In all experiments, peptides were superfused at a rate of 0.3 ml/min.…”

Section: Methodsmentioning

confidence: 99%

Specificity of Repetition Priming: The Role of Chemical Coding

2015

View full text Add to dashboard Cite

We investigate stimulus specificity of repetition priming in a tractable model system; the feeding network of Aplysia. Previous studies primarily focused on an aspect of behavior that is altered during ingestive priming, radula opening. Priming of radula opening occurs when two modulatory peptides [feeding circuit activating peptide (FCAP) and cerebral peptide-2 (CP-2)] are released from the cholinergic command-like neuron cerebral buccal interneuron 2. Effects of FCAP/CP-2 on radula opening motor neurons are cAMP mediated. The present experiments sought to determine whether FCAP/CP-2 and cAMP are also involved in the priming of radula opening during an incompatible activity, i.e., during egestive motor programs. Egestive priming is induced when motor programs are triggered by afferents with processes in the esophageal nerve. We demonstrate that egestive priming is not FCAP/CP-2 mediated. Instead, it is induced by an unrelated peptide (small cardioactive peptide), which exerts PKC-mediated effects. Our data, therefore, suggest that different feeding motor programs are primed via actions of different sets of intercellular and intracellular substances. We suggest that this accounts for the stimulus specificity that can be characteristic of repetition priming. Different stimuli activate different central pattern generator inputs. These inputs release different modulators, which induce functionally distinct motor programs.

show abstract

Release of neuropeptides during intracellular stimulation of single identified Aplysia neurons in culture.

Cited by 32 publications

References 17 publications

Release of peptide cotransmitters from a cholinergic motor neuron under physiological conditions.

Release of peptide cotransmitters from a cholinergic motor neuron under physiological conditions.

Frequency-dependent release of peptide cotransmitters from identified cholinergic motor neurons in Aplysia.

Specificity of Repetition Priming: The Role of Chemical Coding

Contact Info

Product

Resources

About