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Biomedical subjects

A I Selverston

Publications and source records attributed to A I Selverston.

At least 19 recordsLinked to original sources

Pattern generation.

The study of rhythmic motor pattern generation continues to be dominated by preparations in which cellular and circuit mechanisms can be bridged. Using these preparations, basic questions such as how circuits can be modified in order to generate a large number of patterns have begun to be answered. The action of neuromodulators on second messengers and channel proteins can provide a link between molecular studies and behavior. There has been a large increase in the use of computer simulations, and their usefulness as a way of studying pattern generation is growing.

Animals

Mechanisms of gastric rhythm generation in the isolated stomatogastric ganglion of spiny lobsters: bursting pacemaker potentials, synaptic interactions, and muscarinic modulation.

1. The gastric central pattern generator (CPG), located in the stomatogastric ganglion (STG) of the spiny lobster (Panulirus interruptus), is nonrhythmic when deprived of neuromodulatory inputs from anterior ganglia. Leaving these inputs intact in vitro can sustain a gastric rhythm but also introduces numerous, uncontrolled and largely unknown modulatory and synaptic influences that greatly complicate analysis of this CPG. 2. Here we induced gastric rhythms in the isolated STG, by superfusing a specific modulator, the muscarinic agonist, pilocarpine. Muscarinic agents sustain vigorous gastric rhythms in the isolated STG. Our aim was to analyze the pattern-generating functions of the restricted gastric circuit, free of complicating influences from other ganglia, and under specific (muscarinic) modulation. 3. We used combinations of multiple cell hyperpolarizations, photodeletions, and synaptic blockade by picrotoxin to assess the pattern-generating role of individual gastric neurons and to study the activity of subcircuits. 4. Four identified gastric neurons [lateral gastric (LG), dorsal gastric (DG), 2 electrically coupled lateral posterior gastric (2LPGs)] acted as pattern-generating cells. They showed bursting pacemaker potentials (BPPs), i.e., plateau (or driver) potentials that underlay bursts of axonal spikes and slow, interburst depolarizing potentials that underlay repetitive burst activity. LG and DG, at least, became conditional bursters, able to burst repetitively because of intrinsic oscillations. The other gastric neurons behaved mainly as follower cells and derived their rhythmic bursting from synaptic coupling to the pattern-generator cells and from their own intrinsic (but nonoscillatory) properties. 5. The pattern-generating neurons form a novel "kernel" circuit that works by the cooperative interaction of cellular properties and synaptic connectivity. 6. This study constitutes the first complete and fully consistent analysis of pattern generation in the gastric network of the isolated STG. These mechanisms pertain to muscarinic rhythms in particular but also, we suggest, to gastric rhythm generation and CPG function in general. We suggest that 1) rhythmicity normally depends on the induction of bursty membrane properties in at least some component neurons; 2) different subcircuits can produce rhythmic patterns and may be activated by different modulators; and 3) the gastric network shares several important "building blocks" with CPGs that have been analyzed in other systems. 7. Muscarinic inputs are implicated as an important gastric regulator. We compare these responses with the reported modulatory actions of the anterior pyloric modulator (AMP), an identified, putatively cholinergic input interneuron that may act via muscarinic mechanisms.

Animals

Distribution of cholecystokinin-like immunoreactivity within the stomatogastric nervous systems of four species of decapod crustacea.

The distribution of cholecystokinin-like immunoreactivity was studied in the stomatogastric nervous systems, pericardial organs, and haemolymph of four species of decapod crustacea, by using immunocytochemical and radioimmunoassay techniques. Whereas cholecystokinin-like immunoreactivity was found within the stomatogastric nervous systems of all four species, its distribution in each is unique. Two species (Panulirus interruptus and Homarus americanus) have cholecystokinin-like immunoreactivity within fibers and neuropil of the stomatogastric ganglion (STG); two other species (Cancer antenarius and Procambarus clarkii) do not. Further, the cholecystokinin-like immunoreactivity within the STGs of Panulirus and Homarus arise from distinct structures; from a projection of anterior ganglia in Panulirus, and from somata within the posterior motor nerves in Homarus. The staining in the other ganglia of the stomatogastric nervous system also shows some interspecies variability, although it appears to be more highly conserved than staining within the STG. These differences in staining were confirmed by measuring the amount of CCK-like peptide present in tissue extracts of ganglia by radioimmunoassay. In contrast to the variable staining within the STG, all four species have cholecystokinin-like immunoreactivity within the neurosecretory pericardial organs and thoracic segmental nerves. This cholecystokinin-like immunoreactivity is contained within fibers and within varicosities that coat the surface of these structures. The location of this staining and the presence of detectible levels of CCK-like peptide in the haemolymph suggests that CCK-like peptides in decapod crustacea may be utilized as neurohormones.

Animals

A cholecystokinin-like hormone activates a feeding-related neural circuit in lobster.

The peptide hormone cholecystokinin (CCK) contributes to the production of feeding-related behaviour in mammals, but the mechanism by which it exerts its effects remains unclear. The gastric mill neural circuit of lobster is an experimentally accessible model system for studying the hormonal control of feeding-related behaviour. Composed of 11 identified neurons, this circuit produces rhythmic movement of teeth within the stomach. We have previously shown that the gastric mill motor pattern can be modulated by a cholecystokinin-like peptide in vitro. We report here that (1) after feeding, levels of CCK-like peptide in haemolymph increase with the activation of the gastric mill, (2) injections of CCK activate the gastric mill, and (3) a specific CCK antagonist inhibits feeding-induced gastric mill activity. This neatly demonstrates a casual link between in vivo release of a peptide hormone and activation of a neural circuit.

Animals

Cholecystokinin-like peptide is a modulator of a crustacean central pattern generator.

The presence, release, and physiological effects of a cholecystokinin(CCK)-like peptide within the stomatogastric ganglion (STG) of the lobster, Panulirus interruptus, are described. Indirect immunofluorescence with 2 antisera raised against CCK8 was used to determine the distribution of CCK-like immunoreactivity (CCKLI) in the stomatogastric nervous system. CCKLI was demonstrated in the input nerve and the neuropil of the STG and in neuropil and somata in the commissural ganglia (CGs), brain, and eyestalks. None of the somata within the STG displayed CCKLI. The cross-reactivities of the CCK antisera with several peptides were determined using either a radioimmunoassay or an immunoblot assay; the antisera recognized peptides homologous to CCK but did not cross-react significantly with several unrelated peptides. The STG contains 2 central pattern generators (CPGs), the pyloric and the gastric mill CPGs. Bath application of CCK8 to the STG had modulatory effects on both CPGs, which were dose dependent and reversible. CCK increased the spike frequencies and number of spikes per burst of the pyloric rhythm but had little effect on the period. CCK increased the period of the gastric rhythm and produced changes in the spike frequencies, burst lengths, and phases of gastric units. High concentrations of peptide were needed to produce these effects (10(-6) to 10(-4) M). Finally, stimulation of the stomatogastric nerve (stn), which contains fibers immunoreactive to CCK, produced calcium-dependent release of CCK molar equivalents (CCKE) into the STG. The stn was electrically stimulated and the superfusate around the ganglion was collected and assayed for CCKE using a radioimmunoassay. Stimulation produced the release of 37.1 +/- 7.1 fmol (mean +/- SEM), compared to 13.7 +/- 4.9 fmol for unstimulated controls and 4.9 +/- 2.9 fmol in the absence of calcium. These data suggest that a CCK-like peptide is an endogenous modulator of the stomatogastric ganglion of P. interruptus.

Animals

Gastric mill activity in the lobster. III. Effects of proctolin on the isolated central pattern generator.

1. The response of the isolated gastric central pattern generator (CPG) to bath application of proctolin is characterized and compared with the previously analyzed behavioral response. 2. Proctolin had an excitatory effect on the ongoing spontaneous rhythm of "combined" preparations, in which the stomatogastric ganglion (STG) is connected to the esophageal and commissural ganglia by the stomatogastric nerve (STN). The effect started between 20 s and 5 min and was characterized by strongly increased burst durations as well as increased spike rates in all units except the two lateral posterior gastric (LPG) motoneurons. The effect was strongest in the dorsal gastric (DG) and lateral gastric (LG) motoneurons and was accompanied by a phase change of the DG burst. DG continued spiking throughout large parts of the burst of LG and of the gastric mill (GM) motoneurons, which are antagonists of DG. 3. The threshold concentration was approximately 10(-10) M, and the effects were dose dependent and reversible. 4. LG and DG were identified as target cells for the action of proctolin. In LG regenerative plateau properties were induced, as revealed by its long-lasting plateau potentials, sensitivity for triggering inputs, and the occurrence of oscillatory prepotentials. An induction of endogenous bursting in DG was concluded from preparations, in which DG was cycling alone or bursting with a much shorter period duration than other gastric neurons. Hyperpolarization of DG, which normally has no or weak driving power within the gastric network, demonstrated that under the influence of proctolin, firing of DG can accelerate the gastric rhythm from a 27- to a 9-s period duration. 5. Proctolin does not only have a modulatory influence on an ongoing rhythm, but it also can trigger gastric activity. This function was first concluded from proctolin-treated STGs, which, unlike normal preparations, continue bursting if inputs via the STN are blocked. Finally, triggering was demonstrated directly, since isolated STGs that were not oscillating started a gastric rhythm after 20-30 min of perfusion with proctolin. 6. The proctolin-induced changes of the CPG activity in isolated preparations are in agreement with the effect on gastric mill chewing in the intact animal, in which, depending on the dose, different modes of chewing could be elicited.

Animals

Substance P-like immunoreactivity is present in the central nervous system of Limulus polyphemus.

The distribution of substance P-like immunoreactivity (substance P-li) in the central nervous system of Limulus polyphemus was studied by using indirect immunocytochemical techniques. Six bilaterally symmetrical pairs of cell clusters in the circumesophageal connectives and the subesophageal mass contain substance P-li. Two of those pairs are the source of a system of efferent fibers that is involved in the expression of circadian rhythms of photosensitivity by the lateral eye. Substance P-li-containing cells were also observed scattered along the length of the circumesophageal connectives, which contain abundant stained fibers and some terminals. Substance P-li fibers leave through the ventral and dorsal nerves of the posterior circumesophageal ring. The neuropil of the subesophageal mass contains an abundance of stained terminals. Immunoreactive fibers can be seen throughout the length of the two longitudinal connectives of the ventral cord, in discrete fiber tracts in the lateral edges of the interganglionic connectives, and in the dorsal and ventral nerves of abdominal ganglia 1-4. Each of these ganglia contains three pairs of substance P-immunoreactive cell body clusters: an anterolateral, a medial longitudinal, and a medial posterior cluster. Substance P-li fibers entering through the ventral (posterior) nerves form very distinctive fascicles in each side of the ganglia, giving off fibers throughout their length. The neuropil is filled with immunoreactive terminals distributed homogeneously. The anterolateral clusters of the abdominal ganglia may be involved in cardioregulation. The six pairs of clusters in the posterior circumesophageal ring, and perhaps some of those in the abdominal ganglia, are believed to constitute a neurosecretory system, projecting to multiple targets throughout the organism. This system is postulated to modulate various sensory inputs and motor activity, and could be driven by a circadian clock, as well as by other systems responsible for integrated organismic responses.

Animals

Oscillatory neural networks.

Despite the fact that a large number of neuronal oscillators have been described, there are only a few good examples that illustrate how they operate at the cellular level. For most, there is some isolated information about different aspects of the oscillator network, but too little to explain the whole mechanism. Two quite remarkable features do seem to be emerging from ongoing studies, however. One is that there are very few generalizable features common to neural oscillators. Many utilize reciprocal inhibitory circuits and endogenous burst-generating currents to some extent. All that have been well worked out utilize a combination of both cellular and network properties, but little else in the way of common mechanism is noteworthy. Perhaps the most interesting aspect of recent work is the ability of a particular oscillator to produce a large repertoire of different outputs. This is separate and in addition to changes occurring via phasic sensory feedback. It is in fact a radical functional "rewiring" of the network in response to neuromodulators. The CPG circuits represent only the most basic form of a given pattern. Finally, concerning the role of sensory feedback in generating oscillatory patterns, the concept of the CPG as a group of neurons able to produce oscillatory patterns without any sensory feedback is, in our opinion, still valid. There is no doubt that some oscillators may be quite weak when isolated, but they can still produce bursts with firing sequences similar to those seen in vivo. The fact that sensory feedback can both control and enhance the oscillations has never been in doubt. Similarly, entrainment of the pattern by sensory feedback does not mean that the receptor is part of the generator, only that it has access to it (as do command and coordinating fibers). The real question remains: Can a group of cells produce an oscillatory pattern without phasic sensory input? We must answer this affirmatively even for the insect-flight motor CPG, while emphasizing the fact that for this system sensory feedback plays a larger role than in most other CPGs. Most neural oscillators will probably fall on some continuum between those like insect flight, which need and use a large amount of phasic feedback, and those that can oscillate in a near-normal manner without it.

Animals

Synaptic connectivity between cricket auditory interneurons as studied by selective photoinactivation.

Sound detection and localization are important for crickets. Interneurons located in the prothoracic ganglion play a crucial role in the initial processing of the auditory inputs. Two of the most readily recorded and dye-marked auditory interneurons in the prothoracic ganglion of the cricket are the omega cells (ON/1) and the ascenders (AN/2). By using a new photoinactivation technique to selectively inactivate these cells, the synaptic relationship between them could be studied. Our results indicate that the ON/1 cells are connected to each other with reciprocal inhibitory synapses. An ON/1 cell responds to contralateral stimulation with strong inhibition mediated by the other ON/1 cell. When one cell is killed, this inhibition is removed, and a weak excitatory response is unmasked. Unlike the ON/1 cell, AN/2 produces an inhibitory response when stimulated ipsilaterally to the cell body side, and this response is also removed when the ipsilateral ON/1 cell is killed, providing strong evidence that ON/1 is the source of the inhibition. As with the ON/1, the inhibition is replaced by weak excitation.

Animals

Histamine as a neurotransmitter in the stomatogastric nervous system of the spiny lobster.

Histamine is a putative neurotransmitter in mammals and molluscs, but its role in the nervous systems of other animals is not known. This study examines the possibility that histamine is a neurotransmitter in an arthropod. Results show that first, 14 neurons in the stomatogastric ganglion of the spiny lobster respond to histamine. The response is inhibitory, is mediated by an increased conductance to chloride, and desensitizes with repeated applications of histamine. These same 14 neurons receive one type of synaptic potential from two extrinsic neurons, the "through-fibers" of the inferior ventricular nerve. This synaptic potential is also inhibitory, is mediated by an increased conductance to chloride, and is blocked when histamine receptors are desensitized. Second, assays of endogenous histamine indicate that histamine is distributed nonuniformly throughout the stomatogastric nervous system and that its distribution correlates with the axonal pathways and terminal arborizations of the inferior ventricular nerve through-fibers. Lastly, histamine is present in relatively high concentrations in the cell bodies of the through-fibers, whereas it is not detectable in other neurons in the stomatogastric system. These results suggest that histamine may be a transmitter in the lobster.

Action Potentials

Neuropeptide modulation of photosensitivity. II. Physiological and anatomical effects of substance P on the lateral eye of Limulus.

A system of efferent substance P-like immunoreactive fibers innervates the ommatidia of the Limulus lateral eye. Thus, we tested the physiological effects of substance P on the lateral eye by measuring the electroretinogram, a population potential reflecting the photoreceptors' response to light, under different experimental conditions. Substance P had no direct effect on the photoreceptors, but it induced an increase in their responsiveness to test flashes of light. The latency, magnitude, and duration of this reversible modulatory effect was dose-dependent. The lateral eye displays an endogenous circadian rhythm in its responsiveness to light. Application of exogenous substance P in the daytime causes an immediate rise as well as an increase in the nocturnal peak, while injection of one of its antagonists (D-Pro2, D-Phe7, D-Trp9 substance P) in the afternoon retards the normal rise in sensitivity and reduces the nighttime levels. Passive incubation with substance P antibodies at midnight caused a drop to diurnal levels of photosensitivity. Short-term changes in photosensitivity, similar in their nature to the substance P-induced ones, were caused by arousing the subjects. Arousal had an effect on the ongoing circadian rhythm similar to that of substance P application. Thus, the substance P efferent system may regulate neural responsiveness in both a short-term, environmentally induced manner, as well as for level setting in a circadian fashion. The mechanism for substance P-induced increases in photosensitivity involves changes in ommatidial structure: contraction of distal pigment cells, resulting in an increased aperture, and contraction of the retinular cells and rhabdom, resulting in a wider diameter of the latter. These structural modifications result in a greater angle of acceptance and increased light quantum catch.

Animals

Synaptic control of an endogenous pacemaker network.

1. The present study consists of an analysis of the coordinating effects of monosynaptic EPSPs and IPSPs on the discharge of the endogenous pacemaker neurons which drive the pyloric motor system of the spiny lobster. The experiments were performed on isolated nervous systems. 2. An analysis of the characteristic phase response curves to both classes of input (fig. 1) shows that the pyloric oscillator possesses the necessary characteristic for entrainment: i.e. a periodically varying sensitivity to synaptic drive. 3. By repetitive stimulation of either input at frequencies near the endogenous frequency of the PD slow wave, it was possible to entrain the discharge of the pacemaker system to the cyclic stimulus (figs. 2b and 3b). The pyloric discharge tends to occur at different characteristic phase relations in response to the two inputs (figs. 2c and 3c), which reflect features of the corresponding phase response curves (fig. 1). 4. It is argued that the periodic sensitivity of these neurons to synaptic input reflects interactions between the synaptically induced currents and the endogenous currents which underlie the slow wave.

Action Potentials

Neural circuitry underlying oscillatory motor output.

1. The stomatogastric nervous system of lobsters can be used as a model network with which to study the mechanisms involved in the generation of rhythmic behaviour. 2. The stomatogastric ganglion contains about thirty neurons and produces two rhythms, the gastric and the pyloric. 3. The gastric rhythm appears to be derived from the global properties of a twelve-cell network. 4. The pyloric rhythm is driven by a group of three endogenous bursters. 5. Both rhythms are assisted by phasic excitatory input from the two commissural ganglia. 6. Synapses found in this network appear to be located on the finest dendritic branches and are multiterminal.

Animals

Ultrastructure of barnacle giant muscle fibers.

Increasing use of barnacle giant muscle fibers for physiological research has prompted this investigation of their fine structure. The fibers are invaginated by a multibranched system of clefts connecting to the exterior and filled with material similar to that of the basement material of the sarcolemmal complex. Tubules originate from the surface plasma membrane at irregular sites, and also from the clefts They run transversely, spirally, and longitudinally, making many diadic and some triadic contacts with cisternal sacs of the longitudinal sarcoplasmic reticulum. The contacts are not confined to any particular region of the sarcomere. The tubules are wider and their walls are thicker at points of contact with Z material. Some linking of the Z regions occurs across spaces within the fiber which contain large numbers of glycogen particles. A-band lengths are extremely variable, in the range 2.2 microm-20.3 microm (average 5.2 microm) Individual thick filaments have thin (110 A) hollow regions alternating with thick (340 A) solid ones. Bridges between thick filaments occur at random points and are not concentrated into an M band The thin:thick filament ratio is variable in different parts of a fiber, from 3:1 to 6:1. Z bands are basically perforated, but the number of perforations may increase during contraction.

Animals

Neuronal circuit mediating escape responses in crayfish.

The neuronal circuit underlying rapid abdominal flexion in response to phasic tactile stimulation comprises identified afferents, interneurons of two orders, a decision unit, and several motor neurons. The circuit is organized hierarchically as a " cascade" in which electrical synapses predominate at higher levels. Behavioral habituation results from lability at chemical junctions early in the pathway.

Abdomen