Search PubMed⌕ Search

Biomedical subjects

S C Rosen

Publications and source records attributed to S C Rosen.

At least 19 recordsLinked to original sources
PubMed2004

Regulation of afferent transmission in the feeding circuitry of Aplysia.

Although feeding in Aplysia is mediated by a central pattern generator (CPG), the activity of this CPG is modified by afferent input. To determine how afferent activity produces the widespread changes in motor programs that are necessary if behavior is to be modified, we have studied two classes of feeding sensory neurons. We have shown that afferent-induced changes in activity are widespread because sensory neurons make a number of synaptic connections. For example, sensory neurons make monosynaptic excitatory connections with feeding motor neurons. Sensori-motor transmission is, however, regulated so that changes in the periphery do not disrupt ongoing activity. This results from the fact that sensory neurons are also electrically coupled to feeding interneurons. During motor programs sensory neurons are, therefore, rhythmically depolarized via central input. These changes in membrane potential profoundly affect sensori-motor transmission. For example, changes in membrane potential alter spike propagation in sensory neurons so that spikes are only actively transmitted to particular output regions when it is behaviorally appropriate. To summarize, afferent activity alters motor output because sensory neurons make direct contact with motor neurons. Sensori-motor transmission is, however, centrally regulated so that changes in the periphery alter motor programs in a phase-dependent manner.

Animals↗
PubMed2000

A proprioceptive role for an exteroceptive mechanoafferent neuron in Aplysia.

Afferent regulation of centrally generated activity is likely to be more complex than has been established. We show that a neuron that is an exteroceptor can also function as a proprioceptor. We study the Aplysia neuron B21. Previous data suggest that B21 functions as an exteroceptor during the radula closing/retraction phase of ingestive feeding. We show that the tissue innervated by B21, the subradula tissue (SRT), is innervated by a motor neuron (B66) and that B66-induced SRT contractions trigger centripetal spikes in B21. Thus, B21 is also a proprioceptor. To determine whether exteroceptive and proprioceptive activities occur during the same phase of ingestive feeding, we further characterize B66. We show that B66 stimulation does not close or retract the radula. Instead it opens it. Moreover, B66 is electrically coupled to other opening/protraction neurons. Finally, we elicit motor programs in semi-intact preparations and show that during radula opening/protraction we observe B66 activity, SRT contractions, and spikes in B21 that can be eliminated if B66 is indirectly hyperpolarized. B21 is, therefore, likely to act as an exteroceptor during one phase of ingestive feeding and as a proprioceptor during the antagonistic phase. Previous experiments have shown that centripetal spikes in B21 are only transmitted to one follower if they are "gated in" by depolarization. During ingestive programs B21 is centrally depolarized during closing/retraction, but it is not depolarized during opening/protraction. We sought to determine whether there are other followers that receive B21 input when it is not centrally depolarized. We found one such cell. Moreover, we found that stimulation of B21 during radula opening/protraction significantly decreases the duration of this phase of behavior. Thus, proprioceptive activity in B21 is likely to have an impact on motor programs.

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↗
PubMed1998

Effect of a serotonergic extrinsic modulatory neuron (MCC) on radula mechanoafferent function in Aplysia.

The serotonergic metacerebral cells (MCCs) and homologous neurons in related mollusks have been extensively investigated within the context of feeding. Although previous work has indicated that the MCCs exert widespread actions, MCC modulation of sensory neurons has not been identified. We characterized interactions between the MCCs and a cell that is part of a recently described group of buccal radula mechanoafferents. The cell, B21, has a peripheral process in the tissue underlying the chitinous radula [the subradula tissue (SRT)]. Previous studies have shown that B21 can fire phasically during ingestive motor programs and provide excitatory drive to the circuitry active during radula closing/retraction. We now show that activity of B21 can be modulated by serotonin (5-HT) and the MCCs. Centrally, although a slow depolarization is typically recorded in B21 as a result of MCC stimulation, this depolarization does not cause B21 to spike. It can, however, increase B21 excitability enabling a pulse that was previously subthreshold to elicit an action potential in B21. B21 is in fact rhythmically depolarized during the radula closing/retraction phase of ingestive motor programs. Thus central effects of the MCCs on radula mechanoafferent activity are only likely to be apparent while B21 is receiving input from the feeding central pattern generator. Peripherally, radula mechanoafferent neurons can be activated 1) when a mechanical stimulus is applied to the biting surface of the SRT and 2) when the SRT contracts. MCC stimulation and 5-HT modulate B21 responses to both types of stimuli. For example, MCC stimulation and low concentrations of 5-HT cause subthreshold mechanical stimuli applied to the SRT to become suprathreshold. 5-HT and MCC stimulation also enhance SRT contractility. Peripheral effects of MCC activity are also likely to be phase dependent. For example, MCC stimulation does not cause B21 to respond to peripheral stimuli with an afterdischarge. Consequently, radula mechanoafferents are likely to be activated when food is present between the radula halves during radula closing/retraction but are not likely to continue to fire as opening/protraction is initiated. In a similar vein, MCC effects on the contractility of the SRT will only be apparent when contractions are elicited by motor neuron activity. SRT motor neurons are rhythmically activated during ingestive motor programs. Thus we have shown that radula mechanoafferent activity can be modulated by the MCCs and that this modulation is likely to occur in a phase-dependent manner.

Animals↗
PubMed1996

Characterization of buccal motor programs elicited by a cholinergic agonist applied to the cerebral ganglion of Aplysia californica.

Applying the non-hydrolyzable cholinergic agonist carbachol (CCh) to the cerebral ganglion of Aplysia elicits sustained, regular bursts of activity in the buccal ganglia resembling those seen during biting. The threshold for bursting is approximately 10(-4) M. Bursting begins after a 2 to 5 min delay. The burst frequency increases over the first 5 bursts, reaching a plateau value of approximately 3 per minute. Bursting is maintained for over 10 min. Some of the effects of CCh may be attributed to its ability to depolarize and fire CBI-2, a command-like neuron in the cerebral ganglion that initiates biting. CBI-2 is also depolarized by ACh, and by stimulating peripheral sensory nerves. Excitation of CBI-2 caused by carbachol is partially blocked by the muscarinic antagonist atropine. We examined whether CCh-induced bursting is modified in ganglia taken from Aplysia that previously experienced treatments inhibiting feeding, such as satiation, head shock contingent or non-contingent with food, and training animals with an inedible food. No treatment consistently and repeatedly affected the latency, the peak burst period, the length of time that bursting was maintained, or the threshold CCh concentration for eliciting bursting. However, there was a decrease in the rate of the build-up of the buccal ganglion program in previously satiated animals.

Animal Feed↗
PubMed1996

Multiple mechanisms for peripheral activation of the peptide-containing radula mechanoafferent neurons B21 and B22 of Aplysia.

1. Recently a cluster of sensory neurons (peptidergic radula mechanoafferents) has been identified in the buccal ganglion of Aplysia that is likely to play an important role in influencing the activity of feeding motor programs. All of the neurons of this cluster, which includes the identified cells B21 and B22, send axons via the radula nerve to a layer of tissue that lies under the chitinous radula (the subradula tissue). 2. We show that the subradula tissue has contractile properties. In the absence of the CNS, contractions of the subradula tissue are elicited if the subradula tissue is stretched. Alternatively, contractions are elicited when extracellular suction electrodes are used to stimulate buccal nerve 3 or the radula nerve. 3. Previous studies have shown that neurons of the B21/B22 cluster respond to peripherally applied mechanical stimuli. We show that these neurons are also activated when the subradula tissue contracts. Axon spikes (A spikes) can be intracellularly recorded from radula mechanoafferent neurons when contractions of the subradula tissue are elicited either by stretch or by extracellular stimulation of buccal nerve 3. 4. Mechanical stimuli that are subthreshold when applied alone elicit A spikes if they are applied while the subradula tissue is contracting. We postulate that this type of interaction may play an important role in gating sensory input to the feeding central pattern generator.

Action Potentials↗
PubMed1994

Structure, localization, and action of buccalin B: a bioactive peptide from Aplysia.

The cholinergic motor neurons for the accessory radula closer (ARC) contain several neuropeptides that affect muscle contractions. In the present study, we have purified and sequenced a sixth ARC neuropeptide, using a combination of high pressure liquid chromatography and bioassays. This neuropeptide, Gly-Leu-Asp-Arg-Tyr-Gly-Phe-Val-Gly-Gly-Leu-amide, has been named buccalin B (BUCb) because it is significantly homologous to the previously characterized neuropeptide buccalin A. BUCb was found to be two-three times more potent than buccalin A in depressing motor neuron induced contractions.

Amino Acid Sequence↗
PubMed1994

A population of SCP-containing neurons in the buccal ganglion of Aplysia are radula mechanoafferents and receive excitation of central origin.

The rostral cluster of SCP-immunoreactive cells, originally identified in each buccal hemiganglion of juvenile Aplysia, was examined in mature specimens. Immunohistochemical and dye-fill experiments showed that each rostral cluster consists of approximately 40 cells. Although these neurons exhibit heterogeneity of size and shape, all cells project an axon into the radula nerve. Tracing of dye-filled cells showed that they project to the layer of tissue that lines the inner surface of the food-grasping portion of the chitinous radula. This tissue contains SCP-immunoreactive nerve fibers and varicosities in regions corresponding to the projections of dye-filled neurons. Several observations indicate that rostral cluster neurons transduce tactile stimuli applied to the radula surface: (1) each cell responds to touch of a circumscribed receptive field with a rapidly adapting burst of action potentials, (2) the evoked spikes arise abruptly from the resting potential without prepotentials, and (3) the responses persist when central and peripheral synaptic transmission is blocked in high Mg2+, low Ca2+ artificial seawater solutions. These cells, designated radula mechanoafferent (RM) neurons, do not respond to chemical stimuli including NaCl, glutamate, and seaweed extract. The highest density of receptive fields is found on the posterodorsal edges of the radula halves, areas most directly involved in grasping food. The RM neurons are electrically coupled cells, with coupling coefficients ranging from 0.006 to 0.22. They fire phasically during buccal motor programs, even in the absence of peripheral feedback from the radula or other portions of the buccal mass. In radiolabeling studies the RM cells were found to synthesize authentic SCPA and SCPB. Sensorin-A, a peptide that is localized to other Aplysia mechanoafferent neurons, was not detected immunohistochemically in these cells.

Animals↗
PubMed1993

Dopaminergic neuron B20 generates rhythmic neuronal activity in the feeding motor circuitry of Aplysia.

We have identified a buccal neuron (B20) that exhibits dopamine-like histofluorescence and that can drive a rhythmic motor program of the feeding motor circuitry of Aplysia. The cell fires vigorously during episodes of patterned buccal activity that occur spontaneously, or during buccal programs elicited by stimulation of identified cerebral command-like neurons for feeding motor programs. Preventing B20 from firing, or firing B20 at inappropriate times, can modify the program driven by the cerebral feeding command-like neuron CBI-2. When B20 is activated by means of constant depolarizing current it discharges in phasic bursts, and evokes a sustained coordinated rhythmic buccal motor program. The program incorporates numerous buccal and cerebral neurons associated with aspects of feeding responses. The B20-driven program can be reversibly blocked by the dopamine-antagonist ergonovine, suggesting that dopamine may be causally involved in the generation of the program. Although firing of B20 evokes phasic activity in cerebral command-like neurons, the presence of the cerebral ganglion is not necessary for B20 to drive the program. The data are consistent with the notion that dopaminergic neuron B20 is an element within the central pattern generator for motor programs associated with feeding.

Animals↗
PubMed1993

Physiology and biochemistry of peptidergic cotransmission in Aplysia.

The marine mollusc Aplysia, whose simple nervous system facilitates study of the neural basis of behavior, was used to investigate the role of peptidergic cotransmission in feeding behavior. Several novel modulatory neuropeptides were purified and localized to identified cholinergic motoneurons. Physiological and biochemical studies demonstrated that these peptides are released when the motoneurons fire at frequencies that occur during normal behavior, and that the peptides modify the relationship between muscle contraction amplitude and relaxation rate so as to maintain optimal motor output when the intensity and frequency of feeding behavior change.

Amino Acid Sequence↗
PubMed1991

Identification and characterization of cerebral-to-buccal interneurons implicated in the control of motor programs associated with feeding in Aplysia.

We identified candidate neurons in the cerebral ganglion that regulate feeding responses mediated by the buccal ganglion. Backfilling the cerebral-buccal connectives revealed that each cerebral hemi-ganglion contains approximately 20 neurons that project axons to the buccal ganglion. Three M-cluster neurons (CBI-1, CBI-2, CBI-3) and one E-cluster neuron (CBI-4) were identified as cerebral-to-buccal interneurons (CBIs) based on position, morphology, synaptic connections, and ability to drive buccal motor programs (BMPs). CBI-1 responds to touch of the tentacles, lips, and buccal mass. It receives monosynaptic EPSPs from interganglionic, cerebral-to-buccal mechanoafferent (ICBM) neurons and monosynaptically excites buccal cells, some of which are also excited by the ICBMs. Tonic firing of CBI-1 usually evokes a single cycle of BMP activity. CBI-1 phase-shifts the rhythmic BMP driven by firing a dopaminergic neuron in the buccal ganglion. CBI-1 itself exhibits dopamine-like histofluorescence following formaldehyde-glutaraldehyde fixation. CBI-2 is excited by food stimuli applied to the lips. Constant-current intracellular stimulation of CBI-2 produces phasic firing of the cell that reliably evokes a rhythmic BMP that incorporates buccal and cerebral motor neurons, putative pattern-generating and pattern-initiating neurons, and neuromodulatory cells (metacerebral cells). CBI-4 also evokes a rhythmic BMP, but the details of its actions and synaptic effects differ from that of CBI-2. CBI-3 does not evoke a BMP, even though it is excited by food stimuli applied to the lips, and it makes monosynaptic connections (both excitatory and inhibitory) to many follower cells of the other CBIs. Firing of CBI-3 phase-delays the BMP driven by CBI-2. Since its activity is incorporated into BMPs and it provides direct inputs to elements of the feeding circuitry, it may play a role in pattern generation. The distinctive features of the CBIs suggest that the consummatory phase of feeding may be controlled by a population of interneurons that subserve different roles.

Animals↗
PubMed1989

Purification and sequencing of neuropeptides contained in neuron R15 of Aplysia californica.

R15 is a large identified neuron present in the abdominal ganglion of the mollusc Aplysia. Previous studies have indicated that this neuron may play a role in water balance and possibly renovascular functions. A peptidic factor contained in the neuron R15 has been shown to increase the water content of Aplysia. To determine the structure of the peptides contained in R15, we purified the extracts of 820 R15 cells by means of two steps of reverse-phase HPLC. The purification yielded a number of peptides, only one of which, R15 alpha 1, resulted in water uptake when injected into animals. Determination of the amino acid content and sequence analysis of the R15 alpha 1 peptide demonstrated that this peptide contains 38 residues, including two cysteines. The peptide failed to react with iodoacetate, indicating that the two cysteines are connected by a disulfide bridge. To confirm the assigned structure, the peptide was synthesized with a disulfide bridge. The chromatographic properties and bioactivity of the synthetic material were identical to those of the native peptide. Several other R15 peptides were inactive in the bioassay for water uptake. The sequence of one of these peptides (R15 beta) was determined, and it was established that the peptide contains 28 residues. Amino acid analysis of three other peaks was performed. One of these peaks contained a peptide (R15 beta f) whose amino acid composition suggests that it is a fragment of the R15 beta peptide. The other two peaks contained peptides with identical amino acid compositions, suggesting that they are variants of a single peptide (R15 gamma). The amino acid sequences of all the peptides identified in neuron R15 correspond to stretches of a polyprotein encoded by a recently sequenced R15 cDNA.

Amino Acid Sequence↗
PubMed1989

Selective modulation of spike duration by serotonin and the neuropeptides, FMRFamide, SCPB, buccalin and myomodulin in different classes of mechanoafferent neurons in the cerebral ganglion of Aplysia.

An examination of the cellular properties and synaptic outputs of mechanoafferent neurons found on the ventrocaudal surface of the cerebral ganglion of Aplysia indicated that the cerebral mechanoafferent (CM) neurons are a heterogeneous population of cells. Based on changes in action potential duration in response to bath applications of 5-HT in the presence of TEA, CM neurons could be divided into 2 broad classes: mechanoafferents whose spikes broaden in response to 5-HT (CM-SB neurons) and mechanoafferents whose spikes narrow in response to 5-HT (CM-SN neurons). Morphological and electrophysiological studies of the CM-SN neurons indicated that they were comprised of previously identified interganglionic cerebral-buccal mechanoafferent (ICBM) neurons and a novel set of sensory neurons that send an axon into the LLAB cerebral nerve and have perioral zone receptive fields that are similar to those of ICBM neurons. Changes in spike width due to 5-HT were correlated with changes in synaptic output as indicated by the magnitudes of EPSPs evoked in postsynaptic neurons. Electrical stimulation of cerebral nerves and connectives also produced spike narrowing or broadening, and the sign of the effect was a function of the parameters of stimulation. Both heterosynaptic facilitation and heterosynaptic depression of EPSPs evoked in follower cells could be demonstrated. A variety of putative neuromodulators other than 5-HT were also found to affect the duration of action potentials in both classes of CM neurons. FMRFamide had effects opposite to that of 5-HT. SCPB and a recently characterized Aplysia neuropeptide, buccalin, broadened the spikes of both CM classes. Another neuropeptide, myomodulin, decreased the duration of CM-SB neuron spikes but had no effect on CM-SN spikes. Since the CM neurons appear to mediate a variety of competing behaviors, including feeding, locomotion, and defensive withdrawal, the various neuromodulator actions may contribute to the mechanisms whereby behaviors are selected and modified.

Action Potentials↗
PubMed1989

The role of a modulatory neuron in feeding and satiation in Aplysia: effects of lesioning of the serotonergic metacerebral cells.

Food-induced arousal in Aplysia is characterized by a progressive increase in the speed and strength of biting responses elicited by a seaweed stimulus. Data from semi-intact and dissected preparations suggest that the identified, serotonergic, metacerebral cells (MCCs) of the cerebral ganglion contribute to food-induced arousal by enhancing the strength of buccal muscle contractions, and by modulating the output of the central pattern generator for biting movements. In order to test this hypothesis in intact, free-moving animals and to determine if the MCCs play a role in satiation of feeding, the behavior of animals that had their MCCs destroyed by intracellular injection of proteases was compared with that of B Cell-Lesion and Dye injection control animals (Experiment 1) or surgical control animals (Experiment 2). Nonfeeding behaviors such as defensive withdrawal responses, locomotion, and righting reflexes were unaffected by MCC lesioning. Also unaffected by MCC lesioning were appetitive feeding behaviors and the amount of food needed to satiate animals. Significant behavioral deficits in consummatory feeding behaviors, which remained stable for periods exceeding 10 d, were observed in the MCC-lesioned animals but not in controls. Lesioned animals exhibited a slowing of rate of repetitive biting responses by 40% of controls and had reduced magnitudes of repetitive bites, particularly at the end of a testing run of 10 consecutive bites. The deficit in bite magnitude was minimally evident in food-deprived animals (Experiment 1) but became more pronounced as animals were fed to satiation (Experiment 2). MCC-lesioned animals still exhibited a residual build-up of the rate and magnitude of biting responses at the onset of feeding behavior. This suggests that, in addition to the MCCs, there are other sources of modulation that contribute to plasticity of consummatory responses during the food-induced arousal state.

Animals↗
PubMed1983

Lesion of a serotonergic modulatory neuron in Aplysia produces a specific defect in feeding behavior.

The serotonergic metacerebral cells (MCCs) of Aplysia were destroyed by intracellular injection of proteolytic enzyme. MCC-lesioned animals showed alterations of biting responses compared to MCC-sham and B-cell-lesioned control animals, as well as to their own preoperative behavior. The alterations of biting responses included a prolongation of the duration of radula protraction and a lengthening of interbite interval. No changes were observed in non-biting feeding responses and in behaviors unrelated to feeding.

Animals↗