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Biomedical subjects

W J Davis

Publications and source records attributed to W J Davis.

At least 37 records · Page 2Linked to original sources

Neural mechanisms of motor program switching in the mollusc Pleurobranchaea. III. Role fo the paracerebral neurons and other identified brain neurons.

Identified neurons in the cerebropleural ganglion (brain) of the mollusc Pleurobranchaea were stimulated and recorded from intracellularly while recording the identified motor program from buccal muscles (reduced preparation) or nerves (isolated central nervous system). Neurons studied included the metacerebral giant neurons (MCGs), phasic paracerebral neurons (PCp's), polysynaptic excitors of the PCp's (PSEs), type II electrotonic neurons (ETII's), type I electrotonic neurons (ETI's) and several other identified neurons or neuronal classes. Intracellular stimulation of the above identified neurons generally elicited the ingestion motor program or its characteristic components, but never the egestion motor program and seldom its characteristic components. Intracellular recordings from these neurons in the isolated central nervous system preparation while eliciting the ingestion and egestion motor program generally showed cyclic membrane potential oscillations in phase with both motor programs, indicating that these neurons receive synaptic feedback from the ingestion and egestion central pattern generator(s). This study is therefore consistent with the view that an interrelated cluster of brain neurons is specialized to command the ingestion motor program. A neural model of motor program switching in the buccal motor system is formulated, comprising separate command pathways for ingestion and egestion that converge on a common central pattern generator(s).

Animals↗

Recurrent aphthous stomatitis.

Aphthous ulcers are of unknown etiology; both genetic and immunologic origins have been proposed. Lesions are painful, tend to recur and may last up to six weeks. Recurrent aphthous stomatitis must be differentiated from herpesvirus infections and herpangina. No treatment has been uniformly successful, but levamisole shows promise.

Adult↗

Fenoterol dose-response study in children with asthma.

We have studied the effect of fenoterol, a selective beta-2 adrenergic agent, on airway obstruction in children with asthma. The drug was administered orally in single doses of 2.5, 5, and 7.5 mg to 20 children with chronic stable asthma of moderate severity. The mean age of the children was 11.6 yr. Pulmonary function tests were performed as baseline at zero time and at intervals over a 6-hour period after drug administration. Onset of action for all doses was within 1 hr with a peak effect noted at 1.5 to 3 hr, and sustained improvement was observed over the entire 6 hr. The doses of 5 mg and 7.5 mg were equally effective in producing significant improvement of pulmonary function compared to 2.5 mg (p less than 0.05). Side effects remained acceptable for all patients. The 5 and 7.5 mg doses produced significant adverse effects that involved the central nervous and musculoskeletal systems, whereas the 7.5 mg dose caused a significant incidence of tachycardia. Our findings indicate: (1) fenoterol is a potent oral bronchodilator for large and small airways in children, (2) the 7.5 mg dose does not achieve any additive effect over a 5 mg dose; and (3) 5 mg is the optimal oral dose of fenoterol for children from age 8 to 12 yr.

Adolescent↗

Brain oscillator(s) underlying rhythmic cerebral and buccal motor output in the mollusc, Pleurobranchaea californica.

Tonic (d.c.) intracellular depolarization of the previously identified phasic paracerebral feeding command interneurones (PCps) in the brain of the carnivorous gastropod Pleurobranchaea causes oscillatory neural activity in the brain, both before and after transecting the cerebrobuccal connectives. Therefore, cycle-by-cycle ascending input from the buccal ganglion is not essential to cyclic brain activity. Instead the brain contains an independent neural oscillator(s), in addition to the oscillator(s) demonstrated previously in the buccal ganglion (Davis et al. 1973). Transection of the cerebrobuccal connectives immediately reduces the previously demonstrated (Kovac, Davis, Matera & Croll, 1983) long-latency polysynaptic excitation of the PCps by the polysynaptic excitors (PSEs) of the PCps. Therefore polysynaptic excitation of the PCps by the PSEs is mediated by an ascending neurone(s) from the buccal ganglion. The capacity of feeding command interneurones to induce neural oscillation in the isolated brain declines to near zero within 1 h after transection of the cerebrobuccal connectives, suggesting that this capacity is normally maintained by ascending information from the buccal ganglion. The results show that this motor system conforms to a widely applicable general model of the neural control of rhythmic behaviour, by which independent neural oscillators distributed widely in the central nervous system are coupled together to produce coordinated movement.

Action Potentials↗

Organization of synaptic inputs to paracerebral feeding command interneurons of Pleurobranchaea californica. I. Excitatory inputs.

Neurons presynaptic to the phasic paracerebral feeding command interneurons (PCP's; Ref. 55) of Pleurobranchaea were located in the isolated central nervous system (CNS) and studied anatomically by lucifer yellow injection and physiologically by current injection and intracellular recording in normal and ion-substituted seawater during quiescence and fictive feeding. The present paper describes excitatory inputs to PCP's, while the accompanying paper (54) reports inhibitory inputs. Monosynaptic excitors (MSEs) are a group of at least three monopolar neurons per hemiganglion. Two have similar dendritic structures and functional effects. Each MSE monosynaptically excites the PCP's and fires action-potential bursts in phase with PCP bursts during fictive feeding. The class I electrotonic neuron (ETI) is a single, identified monopolar neuron per hemiganglion with a sparse dendritic arborization and no descending axon in the cerebrobuccal connective (CBC). The ETI is coupled with PCP's only by means of a non-rectifying electrical synapse. Paradoxically, ETI receives opposite synaptic inputs from PCP's and fires in antiphase with PCP's during fictive feeding. Class II electrotonic neurons (ETII's) are a group of at least two identified multipolar neurons per hemiganglion with indistinguishable dendritic architectures and similar but distinguishable functional effects. Each cell is coupled with PCP's by means of a nonrectifying electrical synapse. One of the ETII's also delivers graded, long-latency poly-synaptic chemical inputs to PCP's. ETII's have descending axons in the CBC, elicit fictive feeding when depolarized, and fire cyclically and in phase with PCP's during fictive feeding. Polysynaptic excitors (PSEs) are a group of at least two identified monopolar neurons per hemiganglion with similar elaborate dendritic fields and functional effects. Each cell excites PCP's by a long-latency, relatively nongraded polysynaptic pathway. PSEs also have descending axons in the ipsilateral CBC, elicit fictive feeding when depolarized, and fire in phase with PCP's during fictive feeding. PSEs and ETII's are here recognized as subclasses of neurons previously identified as paracerebral neurons. They are inhibited by the same neurons that supply recurrent inhibition to PCP's (47), share excitatory inputs with PCP's, and exhibit a similar "command" capacity. This study thus documents redundancy and functional specialization within a command system controlling a relatively complex rhythmic motor behavior.

Afferent Pathways↗

Organization of synaptic inputs to paracerebral feeding command interneurons of Pleurobranchaea californica. III. Modifications induced by experience.

Phasic paracerebral feeding command interneurons (PCP's) were studied in whole-animal preparations of Pleurobranchaea drawn from four populations with different behavioral histories: food avoidance conditioned, yoked controls, food satiated, and naive. PCP responses to chemosensory food stimuli (liquefied squid) and mechanosensory touch stimuli (tactile stimulation of anterior and posterior structures) were recorded intracellularly, scored blind, and compared quantitatively across the four populations. PCP's from avoidance-conditioned specimens (10, 18, 19) showed decreased excitatory and increased inhibitory responses to food and touch in comparison with naive (untrained) specimens. Control animals did not show these effects. PCP's from satiated specimens showed decreased excitatory and increased inhibitory responses to food and touch in comparison with PCP's from control, naive, and conditioned specimens. Inhibitory postsynaptic potentials (IPSPs) induced in PCP's of conditioned and satiated specimens by food and touch are indistinguishable in amplitude and waveform from IPSPs produced in the same PCP's by the previously described cyclic inhibitory network (CIN; Ref. 13). In addition, tonic paracerebral neurons (PCT's) that lack input from the CIN, are not inhibited but rather are excited in trained and satiated animals. Therefore the inhibitory responses to food and touch by PCP's of conditioned and satiated specimens appear to be mediated by the CIN. This study demonstrates that associative and nonassociative processes (learning and food satiation, respectively) manifest similarly at the level of command interneurons. The findings furnish a neurophysiological explanation for behavioral motivation in Pleurobranchaea, namely, modulation of the balance of excitation/inhibition in command neurons controlling the corresponding behavior. A cellular model of food avoidance learning and food satiation is formulated to account for these data, based on the identified neural circuitry of the paracerebral command system (15, 17).

Animals↗

Theophylline blood levels as a guide to intravenous therapy in children.

A retrospective analysis of the records of 56 children admitted in status asthmaticus was done to assess the impact of serum theophylline levels on subsequent therapeutic decisions. In 39% of the cases, levels obtained following the initial theophylline bolus were below therapeutic range and in 6% they were above therapeutic range. In 31% of instances of theophylline levels obtained during the phase of continuous aminophylline infusion, the physician decided to administer additional theophylline. The median hospital stay was 2.65 days. Monitoring serum theophylline levels following intravenous loading and during continuous infusion provides the physician with a valuable clinical tool and may help to shorten the period of hospitalization for patients in status asthmaticus.

Adolescent↗

Chemoreception in gastropod molluscs: electron microscopy of putative receptor cells.

Scanning and transmission electron microscopy of the external surface of the gastropod mollusc Pleurobranchaea californica has revealed a new exteroreceptor, characterized by dense cilia (ac.200/cell) that project from an intraepithelial soma and exhibit dilated, discoid-shaped tips. The exteroreceptor is found in high densities (up to 5000/mm2) in areas of the body determined by behavioral assay to be chemosensitive, but nowhere else, suggesting that it is a chemoreceptor.

Chemoreceptor Cells↗

Paddle cilia (discocilia) in chemosensitive structures of the gastropod mollusk Pleurobranchaea californica.

Scanning electron microscopy of various regions of the body of the marine gastropod Pleurobranchaea californica (McFarland) has revealed a characteristic cell type that bears cilia with dilated discoid-shaped tips. The tips of the cilia consist of an expansion of the ciliary membrane around a looped distal extension of the axoneme. These kinocilia have been observed in numerous other marine invertebrates and are generally referred to as paddle cilia (Tamarin et al. 1974) or discocilia (Heimler 1978). Although many functions have been proposed for paddle cilia, little empirical evidence supports any of the proposals. In Pleurobranchaea we have found that the distribution of this ciliated cell type corresponds exactly to areas of the body known from behavioral studies (Lee et al. 1974; Davis and Matera 1981) to mediate chemoreception. Transmission electron microscopy of the epithelium lining the rhinophores and tentacles of Pleurobranchaea revealed details of the ultrastructure of these ciliated cells and showed that they are primary receptors. These ciliated receptors lie in a yellow-brown pseudostratified columnar epithelium that superficially resembles the olfactory mucosa of vertebrates.

Animals↗

Interaction between nutrition and theophylline metabolism in children.

The influences on theophylline metabolism are multifactorial, resulting in significant inter- and intrapatient variability in drug responsiveness. Clinical investigations with adult patients have demonstrated the influence of diet on theophylline metabolism following a single drug dose. We have undertaken this study to examine the effect of nutritional factors on theophylline pharmacokinetics in 14 asthmatic children receiving the drug on a chronic basis. For 12-day periods each patient received three separate diets with different proportions of protein and carbohydrate but with constant fat and caloric intake. Significant differences were detected for theophylline half-life, apparent volume of distribution, and metabolic clearance rate. The high-protein diet markedly shortened the drug-elimination half-life relative to a normal diet, and high carbohydrate significantly increased it (both p less than 0.001). Other kinetic parameters confirmed this pattern. Our findings in children clearly establish that nutritional factors have a significant environmental influence on theophylline metabolism during the drug's steady-state pharmacokinetics.

Adolescent↗

Control of feeding motor output by paracerebral neurons in brain of Pleurobranchaea californica.

1. A population of interneurons that control feeding behavior in the mollusk Pleurobranchaea has been analyzed by dye injection and intracellular stimulation/recording in whole animals and reduced preparations. The population consists of 12-16 somata distributed in two bilaterally symmetrical groups on the anterior edge of the cerebropleural ganglion (brain). On the basis of their position adjacent to the cerebral lobes, these cells have been named paracerebral neurons (PCNs). This study concerns pme subset pf [MCs. the large, phasic ones, which have the strongest effect on the feeding rhythm (21). 2. Each PCN sends a descending axon via the ipsilateral cerebrobuccal connective to the buccal ganglion. Axon branches have not been detected in other brain or buccal nerves and hence the PCNs appear to be interneurons. 3. In whole-animal preparations, tonic intracellular depolarization of the PNCs causes them to discharge cyclic bursts of action potentials interrupted by a characteristic hyperpolarization. In all specimens that exhibit feeding behavior, the interburst hyperpolarization is invariably accompanied by radula closure and the beginning of proboscis retraction (the "bite"). No other behavorial effect of PCN stimulation has been observed. 4. In whole-animal preparations, the PCNs are excited by food and tactile stimulation of the oral veil, rhinophores, and tentacles. When such stimuli induce feeding the PCNs discharge in the same bursting pattern seen during tonic PCN depolarization, with the cyclic interburst hyperpolarization phase locked to the bit. When specimens egest an unpalatable object by cyclic buccal movements, however, the PCNs are silent. The PCNs therefore exhibit properties expected of behaviorally specific "command" neurons for feeding. 5. Silencing one or two PCNs by hyperpolarization may weaken but does not prevent feeding induced by natural food stimuli. Single PCNs therefore can be sufficient but are not necessary to induction of feeding behavior. Instead the PCNs presumably operate as a population to control feeding. 6. In isolated nervous system preparations tonic extracellular stimulation of the stomatogastric nerve of the buccal ganglion elicits a cyclic motor rhythm that is similar in general features to the PNC-induced motor rhythm. Bursts of PCN action potentials intercalated at the normal phase position in this cycle intensify the buccal rhythm. Bursts of PCN impulses intercalated at abnormal phase positions reset the buccal rhythm. The PCNs, therefore, also exhibit properties expected of pattern-generator elements and/or coordinating neurons for the buccal rhythm. 7. The PCNs are recruited into activity when the buccal motor rhythm is elicited by stomatogastric nerve stimulation or stimulation of the reidentifiable ventral white cell. The functional synergy between the PCNs and the buccal rhythm is therefore reciprocal. 8...

Animals↗

Functional and structural correlates of cell size in paracerebral neurons of Pleurobranchaea californica.

1. The paracerebral neurons (PCNs) in the brain of the mollusk Pleurobranchaea are a population of 12-16 interneurons that send axons to the buccal ganglion and control cyclic feeding behavior (9). In the present study we show that the PCNs differ in size and that a number of functional and structural properties of the PCNs are closely correlated with cell size. 2. PCN soma diameter varies from about 30 to 120 micrometers. The diameters segregate into two distinct but overlapping populations, which correspond to independently assigned functional classifications of "tonic" and "phasic" PCNs. The mean soma diameters of two populations were 63 and 84 micrometers, respectively. 3. Two morphological features vary systematically with PCN soma size. First, soma diameter, axonal conduction velocity, and extracellular spike amplitude were positively correlated; therefore, PCN axon diameter presumably increases with soma diameter. Second, intrasomatic injection of lucifer yellow revealed that the small, tonic PCNs are multipolar, while the large, phasic PCNs are generally monopolar neurons. 4. Small PCNs discharge tonically in response to sustained current injection and have a weak effect on cyclic motor output recorded from nerves that innervate feeding muscles. In contrast, the large PCNs discharge phasically in bursts of action potentials that are coordinated with the cyclic motor output and have a comparatively strong effect on the rhythm. The motor effects of simultaneous tonic and phasic PCN stimulation are additive. 5. Tonic and phasic PCNs innervate different but partially overlapping populations of feeding motor neurons. Phasic PCNs typically inhibit motor neurons exiting buccal root 3, while tonic PCNs either have no effect or are weakly excitatory. 6. Tonic and phasic PCNs exhibit different intrinsic properties. In comparison with phasic PCNs, tonic PCNs have higher input resistances, higher spontaneous discharge rates at rest potential, lower firing thresholds to intrasomatically injected current, lower absolute voltage thresholds, greater pacemaker sensitivity, and greater total capacitance. 7. Tonic and phasic PCNs exhibit different input properties. Tonic PCNs are recruited before phasic ones during cycylic buccal motor output induced by stomatogastric nerve stimulation. Phasic PCNs receive powerful, cycylic inhibition that is not shared by tonic PCNs. In addition, extracellular stimulation of the large oral veil nerve of the brain excites tonic PCNs but causes a biphasic postsynaptic potential (PSP) in phasic PCNs that has a net inhibitory effect. Some excitatory synaptic input to phasic and tonic PCNs is unshared, while some is shared. 8. It is concluded that these command interneurons obey the size principle discovered earlier in motor neurons (4, 13-16). Cell size per se is not the causal variable, however; instead the underlying causes of the differences between small and large PCNs include different input and output organizations as well as different intrinsic functional and morphological properties.

Animals↗