Biomedical subjects

I Kupfermann

Publications and source records attributed to I Kupfermann.

At least 19 recordsLinked to original sources

PubMed2001

Further studies of bulk and orosensory decrement in producing satiation of feeding in Aplysia.

Prior evidence has suggested that meal satiation in the marine mollusk Aplysia is associated with stretch of the crop. The current data, however, suggest that under some conditions, bulk in the crop can be dissociated from the propensity to feed. The crop was hyper-distended 6 h after a satiating meal of rehydrated seaweed; that is, the crop took in water and therefore contained a greater volume than it had contained immediately after satiation. Animals presented with food 6 h after an initial satiating meal consumed a new meal despite the fact that their crop was distended beyond the level at which they had previously terminated feeding. This unexpected result led to additional experiments designed to study possible orosensory decrement during presentation of food. Orosensory input was assessed by recording from the metacerebral cell (MCC) in free-moving animals. The MCC receives excitatory input in response to chemosensory stimulation of the lips, and exhibited a slow decrement during the course of a meal or during repeated lip stimulation without ingestion. Lesions of the cerebro-buccal connectives abolished the long-term MCC response decrement to lip stimulation. This result suggests that the MCC long-term response decrement to lip stimulation is a product of buccal-ganglion feedback and may not reflect sensory decrement of chemosensory pathways. Therefore, satiation may not produce a change in lip sensitivity to chemosensory input. Our data suggest that one important factor that determines satiation is a stretch stimulus of the posterior esophagus/anterior crop. This stretch stimulus may subside over several hours as the crop contents are redistributed or as receptors slowly adapt.

Action Potentials↗

PubMed2001

Motor program selection in simple model systems.

In recent years, studies of molluscan and crustacean feeding circuits have greatly expanded our knowledge of how the nervous system selects specific behaviors. Increasing use of neurobehavioral studies, and examination of the roles of identified command-like or influential neurons have narrowed the gap between knowledge of circuit connectivity and understanding of the normal behavioral functions of these circuits.

Animals↗

PubMed2001

Cerebral-abdominal interganglionic coordinating neurons in Aplysia.

Three cerebral-abdominal interneurons (CAIs), CC2, CC3, and CC7, were identified in the cerebral ganglion C cluster. The cells send their axons to the abdominal ganglion via the pleural-abdominal connective. CC2 and CC3 are bilaterally symmetrical cells, whereas CC7 is a unilateral cell. CC3 is immunopositive for serotonin and may be the same cell (CB-1) previously described as located in the B cluster rather than the C cluster. We suggest that the full designation of CC3, be CC3(CB-1). All three cells respond to feeding-related inputs. Each CAI has a monosynaptic connection to at least one abdominal ganglion neuron involved in the control of various nonsomatic organs. The CAIs also exert widespread polysynaptic actions in the abdominal and head ganglia. The results suggest that the CAIs may act as interneurons that coordinate visceral responses mediated by the abdominal ganglion, with behaviors such as feeding and head withdrawal, that are controlled by neurons located in the head ganglia of the animal.

Abdomen↗

PubMed2000

Peptide cotransmitter release from motorneuron B16 in aplysia californica: costorage, corelease, and functional implications.

Many neurons contain multiple peptide cotransmitters in addition to their classical transmitters. We are using the accessory radula closer neuromuscular system of Aplysia, which participates in feeding in these animals, to define the possible consequences of multiple modulators converging on single targets. How these modulators are released onto their targets is of critical importance in understanding the outcomes of their modulatory actions and their physiological role. Here we provide direct evidence that the partially antagonistic families of modulatory peptides, the myomodulins and buccalins, synthesized by motorneuron B16 are costored and coreleased in fixed ratios. We show that this release is calcium-dependent and independent of muscle contraction. Furthermore, we show that peptide release is initiated at the low end of the physiological range of motorneuron firing frequency and that it increases with increasing motorneuron firing frequency. The coordination of peptide release with the normal operating range of a neuron may be a general phenomenon and suggests that the release of peptide cotransmitters may exhibit similar types of regulation and plasticity as have been observed for classical transmitters. Stimulation paradigms that increase muscle contraction amplitude or frequency also increase peptide release from motor neuron B16. The net effect of the modulatory peptide cotransmitters released from motorneuron B16 would be to increase relaxation rate and therefore allow more frequent and/or larger contractions to occur without increased resistance to antagonist muscles. The end result of this modulation could be to maximize the efficiency of feeding.

Action Potentials↗

PubMed2000

Diverse synaptic connections between peptidergic radula mechanoafferent neurons and neurons in the feeding system of Aplysia.

The buccal ganglion of Aplysia contains a heterogeneous population of peptidergic, radula mechanoafferent (RM) neurons. To investigate their function, two of the larger RM cells (B21, B22) were identified by morphological and electrophysiological criteria. Both are low-threshold, rapidly adapting, mechanoafferent neurons that responded to touch of the radula, the structure that grasps food during ingestive and egestive feeding movements. Sensory responses of the cells consisted of spike bursts at frequencies of 8-35 Hz. Each cell was found to make chemical, electrical, or combined synapses with other sensory neurons, motor neurons and interneurons involved in radula closure and/or protraction-retraction movements of the odontophore. Motor neurons receiving input included the following: B8a/b, B15, and B16, which innervate muscles contributing to radula closing; and B82, a newly identified neuron that innervates the anterodorsal region of the I1/I3 muscles of the buccal mass. B21 and B22 can affect buccal motor programs by way of their connections to interneurons such as B19 and B64. Fast, chemical, excitatory postsynaptic potentials (EPSPs) produced by RM neurons, such as B21, exhibited strong, frequency-dependent facilitation, a form of homosynaptic plasticity. Firing B21 also produced a slow EPSP in B15 that increased the excitability of the cell. Thus a sensory neuron mediating a behavioral response may have modulatory effects. The data suggest multiple functions for RM neurons including 1) triggering of phase transitions in rhythmic motor programs, 2) adjusting the force of radula closure, 3) switching from biting to swallowing or swallowing to rejection, and 4) enhancing food-induced arousal.

Animals↗

PubMed2000

Outputs of radula mechanoafferent neurons in Aplysia are modulated by motor neurons, interneurons, and sensory neurons.

The gain of sensory inputs into the nervous system can be modulated so that the nature and intensity of afferent input is variable. Sometimes the variability is a function of other sensory inputs or of the state of motor systems that generate behavior. A form of sensory modulation was investigated in the Aplysia feeding system at the level of a radula mechanoafferent neuron (B21) that provides chemical synaptic input to a group of motor neurons (B8a/b, B15) that control closure and retraction movements of the radula, a food grasping structure. B21 has been shown to receive both excitatory and inhibitory synaptic inputs from a variety of neuron types. The current study investigated the morphological basis of these heterosynaptic inputs, whether the inputs could serve to modulate the chemical synaptic outputs of B21, and whether the neurons producing the heterosynaptic inputs were periodically active during feeding motor programs that might modulate B21 outputs in a phase-specific manner. Four cell types making monosynaptic connections to B21 were found capable of heterosynaptically modulating the chemical synaptic output of B21 to motor neurons B8a and B15. These included the following: 1) other sensory neurons, e.g. , B22; 2) interneurons, e.g., B19; 3) motor neurons, e.g., B82; and 4) multifunction neurons that have sensory, motor, and interneuronal functions, e.g., B4/5. Each cell type was phasically active in one or more feeding motor programs driven by command-like interneurons, including an egestive motor program driven by CBI-1 and an ingestive motor program driven by CBI-2. Moreover, the phase of activity differed for each of the modulator cells. During the motor programs, shifts in B21 membrane potential were related to the activity patterns of some of the modulator cells. Inhibitory chemical synapses mediated the modulation produced by B4/5, whereas excitatory and/or electrical synapses were involved in the other instances. The data indicate that modulation is due to block of action potential invasion into synaptic release regions or to alterations of transmitter release as a function of the presynaptic membrane potential. The results indicate that just as the motor system of Aplysia can be modulated by intrinsic mechanisms that can enhance its efficiency, the properties of primary sensory cells can be modified by diverse inputs from mediating circuitry. Such modulation could serve to optimize sensory cells for the different roles they might play.

Animals↗

PubMed2000

Multifunctional neuron CC6 in Aplysia exerts actions opposite to those of multifunctional neuron CC5.

The controls of somatic and autonomic functions often appear to be organized into antagonistic systems. This issue was explored in the bilaterally paired C cluster neuron, CC6, which was found to have properties that suggested that it might function antagonistically to the previously identified multiaction neuron, CC5. Similar to CC5, CC6 is an interganglionic neuron that sends its sole axon to the ipsilateral and contralateral pedal and pleural ganglia. Synaptic inputs to CC6 were opposite to those of CC5. For example, CC6 receives inhibitory inputs from mechanical touch to the lips and tentacles and is excited by firing of C-PR, a neuron involved in the control of a head extension response. Also during rhythmic buccal mass movements CC6 receives synaptic inputs that are out of phase with those received by CC5. CC6 is inhibited during a fictive locomotor program, whereas CC5 is excited, but unlike CC5, the inputs to CC6 are not rhythmic. CC6 has extensive mono- and polysynaptic outputs to many identified and unidentified neurons located in various central ganglia. Firing of CC6 evoked ipsilateral contraction of the transverse muscles of the neck, whereas CC5 contracts longitudinal neck muscles. CC6 monosynaptically inhibits the pedal artery shortener neuron, whereas CC5 monosynaptically excites the pedal artery shortener neuron. Specific motor neurons in the pedal ganglion receive synaptic inputs of opposite sign from CC5 and CC6. Although the inputs and most of the effects of CC6 were opposite to those of CC5, both cells were found to produce polysynaptic excitation of the abdominal ganglion neuron RBhe, a cell whose activity excites the heart. CC5 and CC6 appear to be multifunctional neurons that form an antagonist pair.

Action Potentials↗

PubMed2000

Serotonergic and peptidergic modulation of the buccal mass protractor muscle (I2) in aplysia.

Plasticity of Aplysia feeding has largely been measured by noting changes in radula protraction. On the basis of previous work, it has been suggested that peripheral modulation may contribute to behavioral plasticity. However, peripheral plasticity has not been demonstrated in the neuromuscular systems that participate in radula protraction. Therefore in this study we investigated whether contractions of a major radula protraction muscle (I2) are subject to modulation. We demonstrate, first, that an increase in the firing frequency of the cholinergic I2 motoneurons will increase the amplitude of the resulting muscle contraction but will not modulate its relaxation rate. We show, second, that neuronal processes on the I2 muscle are immunoreactive to myomodulin (MM), RFamide, and serotonin (5-HT), but not to small cardioactive peptide (SCP) or buccalin. The I2 motoneurons B31, B32, B61, and B62 are not immunoreactive to RFamide, 5-HT, SCP, or buccalin. However, all four cells are MM immunoreactive and are capable of synthesizing MMa. Third, we show that the bioactivity of the different modulators is somewhat different; while the MMs (i.e., MMa and MMb) and 5-HT increase I2 muscle relaxation rate, and potentiate muscle contraction amplitude, MMa, at high concentrations, depresses muscle contractions. Fourth, our data suggest that cAMP at least partially mediates effects of modulators on contraction amplitude and relaxation rate.

Acetylcholine↗

PubMed1999

Insulin prohormone processing, distribution, and relation to metabolism in Aplysia californica.

The first Aplysia californica insulin gene is characterized and its proteolytic processing from prohormone to final peptides elucidated using a combination of biochemical and mass spectrometric methods. Aplysia insulin (AI) is one of the largest insulins found, with a molecular weight of 9146 Da, and an extended A chain compared with other invertebrate and vertebrate insulins. The AI prohormone produces a series of C peptides and also a unique N-terminally acetylated D peptide. AI-producing cells are restricted to the central region of the cerebral ganglia mostly within the F and C clusters, and AI is transported to neurohemal release sites located on the upper labial and anterior tentacular nerves. The expression of AI mRNA decreases when the animal is deprived of food, and injections of AI reduce hemolymph glucose levels, suggesting that the function of insulin-regulating metabolism has been conserved.

Amino Acid Sequence↗

PubMed1999

Decrement of the response of a serotonergic modulatory neuron (the metacerebral cell) in Aplysia, during repeated presentation of appetitive (food) stimuli.

Application of food (seaweed, SW) stimuli to the lips evokes a burst of metacerebral cell (MCC) spikes, and it was found in free-moving animals that repeated presentation of the stimulus was associated with a rapid decrement of the evoked responses, even in the absence of ingestion of the food. To aid in discriminating between mechanisms that may be responsible for this decrement, SW was applied repeatedly to the lip ipsilateral or contralateral to one of the paired MCCs, and then generalization of the response decrement was tested by applying a SW stimulus to the opposite (non-stimulated) receptive field. There was statistically significant generalization of response decrement and the amount of generalization appeared to be a function of whether the decrementing stimuli were presented on the side ipsilateral vs. contralateral to the recorded MCC. The overall data suggest that MCC response decrement to repeated food stimuli results in a process analogous to behavioral habituation, and the data are consistent with a simple neural model.

Animals↗

PubMed1999

Actions of a pair of identified cerebral-buccal interneurons (CBI-8/9) in Aplysia that contain the peptide myomodulin.

A combination of biocytin back-fills of the cerebral-buccal connectives and immunocytochemistry of the cerebral ganglion demonstrated that of the 13 bilateral pairs of cerebral-buccal interneurons in the cerebral ganglion, a subpopulation of 3 are immunopositive for the peptide myomodulin. The present paper describes the properties of two of these cells, which we have termed CBI-8 and CBI-9. CBI-8 and CBI-9 were found to be dye coupled and electrically coupled. The cells have virtually identical properties, and consequently we consider them to be "twin" pairs and refer to them as CBI-8/9. CBI-8/9 were identified by electrophysiological criteria and then labeled with dye. Labeled cells were found to be immunopositive for myomodulin, and, using high pressure liquid chromatography, the cells were shown to contain authentic myomodulin. CBI-8/9 were found to receive synaptic input after mechanical stimulation of the tentacles. They also received excitatory input from C-PR, a neuron involved in neck lengthening, and received a slow inhibitory input from CC5, a cell involved in neck shortening, suggesting that CBI-8/9 may be active during forward movements of the head or buccal mass. Firing of CBI-8 or CBI-9 resulted in the activation of a relatively small number of buccal neurons as evidenced by extracellular recordings from buccal nerves. Firing also produced local movements of the buccal mass, in particular a strong contraction of the I7 muscle, which mediates radula opening. CBI-8/9 were found to produce a slow depolarization and rhythmic activity of B48, the motor neuron for the I7 muscle. The data provide continuing evidence that the small population of cerebral buccal interneurons is composed of neurons that are highly diverse in their functional roles. CBI-8/9 may function as a type of premotor neuron, or perhaps as a peptidergic modulatory neuron, the functions of which are dependent on the coactivity of other neurons.

Animals↗

PubMed1999

C-PR neuron of Aplysia has differential effects on "Feeding" cerebral interneurons, including myomodulin-positive CBI-12.

Head lifting and other aspects of the appetitive central motive state that precedes consummatory feeding movements in Aplysia is promoted by excitation of the C-PR neuron. Food stimuli activate C-PR as well as a small population of cerebral-buccal interneurons (CBIs). We wished to determine if firing of C-PR produced differential effects on the various CBIs or perhaps affected all the CBIs uniformly as might be expected for a neuron involved in producing a broad undifferentiated arousal state. We found that when C-PR was fired, it produced a wide variety of effects on various CBIs. Firing of C-PR evoked excitatory input to a newly identified CBI (CBI-12) the soma of which is located in the M cluster near the previously identified CBI-2. CBI-12 shares certain properties with CBI-2, including a similar morphology and a capacity to drive rhythmic activity of the buccal-ganglion. Unlike CBI-2, CBI-12 exhibits myomodulin immunoreactivity. Furthermore when C-PR is fired, CBI-12 receives a polysynaptic voltage-dependent slow excitation, whereas, CBI-2 receives relatively little input. C-PR also polysynaptically excites other CBIs including CBI-1 and CBI-8/9 but produces inhibition in CBI-3. In addition, firing of C-PR inhibits plateau potentials in CBI-5/6. The data suggest that activity of C-PR may promote the activity of one subset of cerebral-buccal interneurons, perhaps those involved in ingestive behaviors that occur during the head-up posture. C-PR also inhibits some cerebral-buccal interneurons that may be involved in behaviors in which C-PR activity is not required or may even interfere with other feeding behaviors such as rejection or grazing, that occur with the head down.

Animals↗

PubMed1999

Modulation of radula opener muscles in Aplysia.

We observed fibers immunoreactive (IR) to serotonin (5-HT), the myomodulins (MMs), and FMRFamide on the I7-I10 complex in the marine mollusk Aplysia californica. The I7-I10 muscle complex, which produces radula opening, is innervated primarily by one motor neuron, B48. B48 is MM-IR and synthesizes authentic MM(A). When B48 is stimulated in a physiological manner, cAMP levels are increased in opener muscles. cAMP increases also are seen when the MMs are applied to opener muscles but are not seen with application of the B48 primary neurotransmitter acetylcholine (ACh). Possible physiological sources of 5-HT and FMRFamide are discussed. When modulators are applied to resting opener muscles, changes in membrane potential are observed. Specifically, 5-HT, MM(B), and low concentrations of MM(A) all depolarize muscle fibers. This depolarization is generally not sufficient to elicit myogenic activity in the absence of neural activity under "rest" conditions. However, if opener muscles are stretched beyond rest length, stretch- and modulator-induced depolarizations can summate and elicit contractions. This only occurs, however, if "depolarizing" modulators are applied alone. Thus other modulators (i.e., FMRFamide and high concentrations of MM(A)) hyperpolarize opener muscle fibers and can prevent depolarizing modulators from eliciting myogenic activity. All modulators tested affected parameters of motor neuron-elicited contractions of opener muscles. MM(B) and 5-HT increased contraction size over the range of concentrations tested, whereas MM(A) potentiated contractions when it was applied at lower concentrations but decreased contraction size at higher concentrations. FMRFamide decreased contraction size at all concentrations and did not affect relaxation rate. Additionally, the MMs and 5-HT increased muscle relaxation rate, decreased contraction latency, and decreased the rate at which tension was developed during motor neuron-elicited muscle contractions. Thus these modulators dramatically affect the ability of opener muscles to follow activity in the opener motor neuron B48. The possible physiological significance of these findings is discussed.

Animals↗

PubMed1998

Evidence that hemolymph glucose in Aplysia californica is regulated but does not affect feeding behavior.

Hemolymph glucose increased following a meal of a commercially available dried seaweed (laver) in Aplysia californica (Aplysia). Glucose injected into the hemocoel did not affect meal size, bite latencies, swallowing rate, or 24-hr food intake. The authors found that injection of a homogenate of nerves containing a putative Aplysia insulin-like substance decreased hemolymph glucose. The nerve homogenate, however, did not affect feeding behavior. Injection of 2-deoxy-D-glucose was found to increase hemolymph glucose, an indication of gluco-privation, but instead of increasing feeding it either had no effect or, at high doses, debilitated animals and interfered with feeding. These studies suggest that glucose may be physiologically regulated in Aplysia, but it does not appear to play a role in the control of feeding behavior.

Analysis of Variance↗

PubMed1997

Ganglionic distribution of inputs and outputs of C-PR, a neuron involved in the generation of a food-induced arousal state in Aplysia.

Cerebral neuron C-PR is thought to play an important role in the appetitive phase of feeding behavior of Aplysia. Here, we describe the organization of input and output pathways of C-PR. Intracellular dye fills of C-PR revealed extensive arborization of processes within the cerebral and the pedal ganglia. Numerous varicosities of varying sizes may provide points of synaptic inputs and outputs. Blocking polysynaptic transmission in the cerebral ganglion eliminated the sensory inputs to C-PR from stimuli applied to the rhinophores or tentacles, indicating that this input is probably mediated by cerebral interneurons. Identified cerebral mechanoafferent sensory neurons polysynaptically excite C-PR. Stimulation of the eyes and rhinophores with light depresses C-PR spike activity, and this effect also appears to be mediated by cerebral interneurons. C-PR has bilateral synaptic actions on numerous pedal ganglion neurons, and also has effects on cerebral neurons, including the MCC, Bn cells, CBIs and the contralateral C-PR. Although the somata of these cerebral neurons are physically close to C-PR, experiments using high divalent cation-containing solutions and cutting of various connectives indicated that the effects of C-PR on other cerebral ganglion neurons (specifically Bn cells and the MCC) are mediated by interneurons that project back to the cerebral ganglion via the pedal and pleural connectives. The indirect pathways of C-PR to other cerebral neurons may help to ensure that consummatory motor programs are not activated until the appropriate appetitive motor programs, mediated by the pedal ganglia, have begun to be expressed.

Action Potentials↗

PubMed1997

Different roles of neurons B63 and B34 that are active during the protraction phase of buccal motor programs in Aplysia californica.

The buccal ganglion of Aplysia contains a central pattern generator (CPG) that organizes sequences of radula protraction and retraction during food ingestion and egestion. Neurons B63 and B34 have access to, or are elements of, the CPG. Both neurons are depolarized along with B31/B32 during the protraction phase of buccal motor programs. Both cells excite the contralateral B31/B32 neurons and inhibit B64 and other neurons active during the retraction phase. B63 and B34 also both have an axon exiting the buccal ganglia via the contralateral cerebrobuccal connective. Despite their similarities, B63 and B34 differ in a number of properties, which reflects their different functions. B63 fires during both ingestion and egestion-like buccal motor programs, whereas B34 fires only during egestion-like programs. The bilateral B63 neurons, along with the bilateral B31 and B32 neurons, act as a single functional unit. Sufficient depolarization of any of these neurons activates them all and initiates a buccal motor program. B63 is electrically coupled to both the ipsilateral and the contralateral B31/B32 neurons but monosynaptically excites the contralateral neurons with a mixed electrical and chemical excitatory postsynaptic potential (EPSP). Positive feedback caused by electrical and chemical EPSPs between B63 and B31/B32 contributes to the sustained depolarization in B31/B32 and the firing of B63 during the protraction phase of a buccal motor program. B34 is excited during the protraction phase of all buccal motor programs, but, unlike B63, it does not always reach firing threshold. The neuron fires in response to current injection only after it is depolarized for 1-2 s or after preceding buccal motor programs in which it is depolarized. Firing of B34 produces facilitating EPSPs in the contralateral B31/B32 and B63 neurons and can initiate a buccal motor program. Firing in B34 is strongly correlated with firing in the B61/B62 motor neurons, which innervate the muscle (I2) responsible for much of protraction. B34 monosynaptically excites these motor neurons. B34 firing is also correlated with firing in motor neuron B8 during the protraction phase of a buccal motor program. B8 innervates the I4 radula closer muscle, which in egestion movements is active during protraction and in ingestion movements is active during retraction. B34 has a mixed, but predominantly excitatory, effect on B8 via a slow conductance-decrease EPSP. Thus firing in B34 leads to amplification of radula protraction that is coupled with radula closing, a pattern characteristic of egestion.

Animals↗

PubMed1996

Costorage and corelease of modulatory peptide cotransmitters with partially antagonistic actions on the accessory radula closer muscle of Aplysia californica.

Many neurons that contain a classical neurotransmitter also contain modulatory peptides, but it has been difficult to establish unequivocally that these peptides are functional cotransmitters. Here, we provide evidence for functional cotransmission in a neuromuscular system of Aplysia. Using immunocytochemical techniques, we localize members of two peptide families, the small cardioactive peptides (SCPs) and the buccalins (BUCs), to a single subset of dense-core vesicles in the terminals of the cholinergic motorneuron B15. We describe a new preparation and method for the direct detection of released peptides and show that the SCPs and BUCs are released when neuron B15 is intracellularly stimulated. Consistent with their subcellular localization, the SCPs and BUCs are released in a stoichiometric ratio that is constant across conditions that change the absolute amount of peptides released. Peptide release is calcium-dependent but does not require muscle contractions. Thus, the release cannot be attributed to a displacement of peptides that may be present in the extracellular space. In previous studies, we characterized the physiological firing patterns of neuron B15. Here, we simulate these firing patterns and show that peptide release occurs. Additionally, we find that significant quantities of material are released under behaviorally relevant conditions. We find that concentrations of released peptides in the muscle are in the concentration range in which exogenously applied peptides exert characterized modulatory actions on muscle contractions. Together, our findings provide strong support for the hypothesis that peptides contained in neuron B15 are functional cotransmitters.

Animals↗

PubMed1996

Release of peptide cotransmitters in Aplysia: regulation and functional implications.

To gain insights into the physiological role of cotransmission, we measured peptide release from cell B15, a motorneuron that utilizes ACh as its primary transmitter but also contains putative peptide cotransmitters, the small cardioactive peptides (SCPs) and the buccalins (BUCs). All stimulation parameters used were in the range in which B15 fires in freely moving animals. We stimulated neuron B15 in bursts and systematically varied the interburst interval, the intraburst frequency, and burst duration. Both peptides were preferentially released when B15 was stimulated at higher intra- or interburst frequencies or with longer burst durations. Across stimulation patterns, the amount of peptide released depended on the mean frequency of stimulation and was independent of the specific pattern of stimulation. The parameters of stimulation that produce a larger release of peptides correspond to those that evoke larger contractions. Large and frequent contractions are likely to fuse or summate, thus disrupting the rhythmic behavior mediated by the muscle innervated by motorneuron B15. Because the combined effect of the SCPs and BUCs is to accelerate the relaxation and shorten the duration of muscle contractions, these peptides reduce the probability of the disruptive fusion or summation of muscle contractions. Because these cotransmitters regulate an aspect of muscle contractions that is not controlled by acetylcholine (ACh), the primary transmitter of B15, we suggest that peptides and ACh form parallel but functionally distinct lines of transmission at the neuromuscular junction. Both types of transmission may be necessary to ensure that behavior remains efficient over a wide range of conditions.

Animals↗