PubMed Health⌕ Search

Biomedical subjects

P A Getting

Publications and source records attributed to P A Getting.

At least 19 recordsLinked to original sources

Parametric features of habituation of swim cycle number in the marine mollusc tritonia diomedea.

When repeatedly elicited, the oscillatory escape swim of the marine mollusc Tritonia diomedea undergoes habituation of the number of cycles per swim. Because the neural circuit for this behavior is reasonably well understood, a cellular analyses of habituation in Tritonia is feasible. Since such a study must ultimately relate cellular correlates to behavioral modifications, we have sought to increase our understanding of the parametric features of cycle number habituation in Tritonia. Habituation was compared when using different intertrial intervals, repeated training sessions, and different stimulus locations. Stimulus site generalization of habituation was demonstrated, suggesting that at least one site of plasticity underlying habitation is located postsynaptic to the sensory neurons for the response. Dishabituation from an above-zero baseline response level was not obtained. An isolated brain preparation was tested as a potential simplified system for cellular studies of habituation mechanisms. Repeated stimulation of a nerve containing sensory afferent processes resulted in a progressive reduction of swim motor program cycle number, with a rate similar to that seen in the behavior. Together, these findings: (1) establish a set of parametric features of cycle numbers habituation to be explained by physiological studies; (2) suggest that at least one circuit modification underlying the habituation is located among the circuit interneurons; and (3) indicate that the isolated brain preparation may serve as a useful neural analogue for studies of the cellular mechanisms of cycle number habituation in Tritonia.

Animals↗

Habituation and iterative enhancement of multiple components of the Tritonia swim response.

To understand the relationship between memory storage sites in the brain and learned changes in behavior, the learned behavior must be characterized. However, even simple types of learning may be quite complex. Repeated elicitation of the Tritonia swim produced multiple changes in the response. Several types of acquisition curves were observed in a single experiment depending on the response component measured. Habituation (response decrement) and iterative enhancement (response facilitation) occurred simultaneously in different swim components. The acquisition curve for one component could be modulated by stimulus strength. Because the Tritonia swim neural network is well studied, it may be possible to causally relate experience-dependent behavioral changes to the underlying memory trace in this marine mollusk.

Animals↗

Dynamic neuromodulation of synaptic strength intrinsic to a central pattern generator circuit.

Motor circuits are often thought to be physically separate from their neuromodulatory systems. We report here a counter example, where neurons within a circuit appear to modulate synaptic properties of that same circuit during its normal operation. The dorsal swim interneurons (DSIs) are members of the central pattern generator circuit for escape swimming in the mollusc Tritonia diomedea. However, DSI stimulation also rapidly enhances the synaptic potentials evoked by another neuron in the same circuit onto its follower cells. This modulatory action appears to be mediated by serotonin (5-hydroxytryptamine); the DSIs are serotonin-immunoreactive, and bath-application of serotonin mimics and occludes the effect of DSIs. These results indicate that during the escape swim, circuit connection strengths are dynamically controlled by the activity of neurons within the circuit itself. This 'intrinsic neuromodulation' may be important for the animal's initial decision to swim, the generation of the swim motor programme itself, and certain types of learning.

Animals↗

Modulation of swimming in Tritonia: excitatory and inhibitory effects of serotonin.

1. In the mollusc Tritonia escape swimming is produced by a network of central pattern generator (CPG) neurons. The purpose of this study was to determine which neurotransmitters might be involved in the swim system. 2. Injection of serotonin (5HT) into whole animals elicited swimming followed by a long-lasting inhibition of swimming. In isolated brain preparations, bath-applied 5HT elicited a swim pattern at short latency and also caused a long-lasting inhibition of the swim pattern. The activation of swimming by 5HT was associated with a tonic depolarization of cerebral cell 2 (C2) and the dorsal swim interneurons (DSI) which form part of the swim CPG network. 3. In isolated brain preparations, bath applied glycine, histamine, proctolin, and FMFRamide had no effect on the swim motor pattern elicited by electrical stimulation of a peripheral nerve. Aspartate, carbacol, dopamine, glutamate, octopamine, pilocarpine, and small cardioactive peptide-B (SCPB) inhibited the activation of swimming by nerve stimulation. 4. The 5HT antagonists cyproheptidine, tryptamine, and 7-methyltryptamine had no effect on swimming, but methysergide and fenfluramine inhibited swimming to both normal sensory stimuli and exogenously applied 5HT. 5. Staining with a polyclonal antibody indicated that one class of CPG neurons, the dorsal swim interneurons (DSI), was immunoreactive for 5HT.

Animals↗

Respiratory-modulated and phrenic afferent-driven neurons in the cervical spinal cord (C4-C6) of the fluorocarbon-perfused guinea pig.

The potential contributions of cervical spinal interneurons to the neural control of respiration have been investigated by extracellularly recording the patterns of activity of neurons in the C4-C6 spinal cord during fictive respiration in the fluorocarbon-perfused, adult guinea pig. Two types of neurons were recorded: respiratory-modulated neurons, whose activity was modulated with respiration, and phrenic-driven neurons, which were excited by electrical stimulation of the phrenic nerve. Respiratory-modulated neurons (n = 20) could be divided into inspiratory, expiratory, and phase-spanning neurons, based on their patterns of activity during fictive respiration. Respiratory-modulated neurons showed varying dependencies on the type of breathing; during spontaneous augmented breaths, one-half exhibited patterns of activity that were significantly different to those seen during normal, fictive respiration, whereas the other half of the respiratory-modulated neurons showed similar patterns of activity during both normal and augmented breaths. Phrenic-driven neurons (n = 22) could be divided into short-latency (7-12 ms), moderate-latency (12-25 ms), and inhibited neurons, but were only occasionally and weakly modulated with respiration. The results suggest that respiratory-modulated C4-C6 spinal neurons may contribute to the neural control of respiration, with different subpopulations specialized for different types of respiratory tasks, and that phrenic-driven neurons may be interposed in sensory or reflex pathways, such as the spinothalamic tract or phrenic-to-phrenic inhibitory reflex.

Animals↗

Medullary respiratory neurons in the guinea pig: localization and firing patterns.

The location and firing patterns of medullary respiratory neurons have been described in a small number of species. The cat has been the most widely studied species, but some potentially important differences have recently been noted in others. A more complete survey of species is required to determine the significance of these differences. We describe the location and firing patterns of respiratory neurons in the medulla of anesthetized, paralyzed and mechanically ventilated adult guinea pigs. Extracellular single-unit recordings were made from the medulla, their phase relationship with phrenic nerve activity used to define them as respiratory and their location marked with fast green. Respiratory units were concentrated ventrolateral to the nucleus tractus solitarius (NTS) and within and surrounding the nucleus ambiguus (NA), corresponding to the dorsal respiratory group (DRG) and ventral respiratory group (VRG) of the cat, respectively. Most DRG respiratory units were inspiratory, while the VRG contained equal numbers of inspiratory and expiratory units. The DRG and VRG both contained early, late and constant-frequency inspiratory and expiratory units. In general, these findings are similar to those in other mammalian species examined, consistent with these basic aspects of the respiratory network being highly conserved.

Action Potentials↗

Excitatory effects of thyrotropin-releasing hormone on neurons within the nucleus ambiguus of adult guinea pigs.

The electrophysiological effects of thyrotropin-releasing hormone (TRH) on neurons within the nucleus ambiguus (NA) of adult guinea pigs were studied using an in vitro brain stem slice preparation. In 0.01-1.0 micron TRH, NA neurons depolarized (25/39), expressed enhanced postinhibitory rebound (8/8 tested), or exhibited oscillations of the membrane potential (17/39). Because the amplitude of postinhibitory rebound in tetrodotoxin (TTX) at various membrane potentials was not altered by TRH, it suggests that TRH enhanced postinhibitory rebound indirectly by depolarizing the cell membrane. The membrane potential oscillations in NA neurons were persistent in TTX and their frequency was dependent on the membrane potential, suggesting that these oscillations were due to intrinsic membrane properties and not to synaptic inputs. The excitation of NA neurons in vitro by TRH suggests that endogenous TRH may modulate the activity of neurons involved in the regulation of respiratory and autonomic function.

Action Potentials↗

Electrophysiological properties of neurons within the nucleus ambiguus of adult guinea pigs.

1. The purpose of this study was to determine the electrophysiological properties of neurons within the region of the nucleus ambiguus (NA), an area that contains the ventral respiratory group. By the use of an in vitro brain stem slice preparation, intracellular recordings from neurons in this region (to be referred to as NA neurons, n = 235) revealed the following properties: postinhibitory rebound (PIR), delayed excitation (DE), adaptation, and posttetanic hyperpolarization (PTH). NA neurons were separated into three groups on the basis of their expression of PIR and DE: PIR cells (58%), DE cells (31%), and Non cells (10%). Non cells expressed neither PIR nor DE and no cells expressed both PIR and DE. 2. PIR was a transient depolarization that produced a single action potential or a burst of action potentials when the cell was released from hyperpolarization. In the presence of tetrodotoxin (TTX), the maximum magnitude of PIR was 7-12 mV. Under voltage-clamp conditions, hyperpolarizing voltage steps elicited a small inward current during the hyperpolarization and a small inward tail current on release from hyperpolarization. These currents, which mediate PIR, were most likely due to Q-current because they were blocked with extracellular cesium and were insensitive to barium. 3. DE was a delay in the onset of action potential firing when cells were hyperpolarized before application of depolarizing current. When cells were hyperpolarized to -90 mV for greater than or equal to 300 ms, maximum delays ranged from 150 to 450 ms. The transient outward current underlying DE was presumed to be A-current because of the current's activation and inactivation characteristics and its elimination by 4-aminopyridine (4-AP). 4. Adaptation was examined by applying depolarizing current for 2.0 s and measuring the frequency of evoked action potentials. Although there was a large degree of variability in the degree of adaptation, PIR cells tended to express less adaptation than DE and Non cells. Nearly three-fourths of all NA neurons adapted rapidly (i.e., 50% adaptation in less than 200 ms), but PIR cells tended to adapt faster than DE and Non cells. PTH after a train of action potentials was relatively rare and occurred more often in DE cells (43%) and Non cells (33%) than in PIR cells (13%). PTH had a magnitude of up to 18 mV and time constants that reflected the presence of one (1.7 +/- 1.4 s, mean +/- SD) or two components (0.28 +/- 0.13 and 4.1 +/- 2.2 s).(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Preservation of integrative function in a perfused guinea pig brain.

The mammalian brain has been one of the most difficult organs to maintain using artificial perfusion. Normal biochemistry, histology, and electrophysiology of the brain have been demonstrated for limited periods in vitro, but it has been more difficult to maintain complex, integrative neuronal activity such as the electroencephalogram (EEG) or programmed motor output. Normal motor output, other than reflex activity, has not previously been demonstrated in a perfused brain preparation. This paper reports the first preservation of normal function in a complete motor network, including intact afferent and efferent pathways, during perfusion of the mammalian brain. The brain, rostral spinal cord and peripheral nervous system of the guinea pig were perfused in situ using an artificial blood containing the oxygen carrier, perfluorotributylamine (FC-43). This preparation was maintained normothermic, whereas many other perfused brain preparations have been maintained hypothermic to prolong viability. Survival was enhanced by the addition of HEPES buffer to the perfusion medium, probably by increasing carbon dioxide transport. The duration of normal EEG was extended to 8 h. Spontaneous respiratory motor output with normal waveform and temporal pattern was recorded from the phrenic nerve for an average of 6 h. The respiratory motor output responded appropriately to blood pCO2, temperature, blood flow, drug concentrations, and electrical stimulation of vagal afferent fibers. This preparation represents a significant advance in the ability to preserve neural function during perfusion, and should offer advantages for studying cellular electrophysiology of intact, functioning neural networks, as well as neurochemistry and neuropharmacology.

Animals↗

Biophysical properties of hypoglossal neurons in vitro: intracellular studies in adult and neonatal rats.

A brain stem slice preparation from adult and neonatal (less than or equal to 12 days old) rats and intracellular recordings were used to examine the cellular properties of neurons within the hypoglossal (HYP) nucleus. Resting membrane potential (Vm) for adult hypoglossal neurons was -80 +/- 2 (SE) mV. Rheobase was 2.1 +/- 0.4 nA, and input resistance (RN) was 20.8 +/- 1.5 M omega and decreased during the hyperpolarizing period ("sag"). Compared with adult HYP cells, newborn HYP neurons had significantly lower resting potentials (Vm = -73 +/- 2 mV), lower rheobase (0.7 +/- 0.2 nA), and higher RN (27.6 +/- 3.9 M omega). Single action potentials, elicited by short depolarizing-current pulses, were followed by a slow afterhyperpolarization in adult [6.4 +/- 0.3 mV, time constant (tc) 31.0 +/- 1.2 ms] and newborn cells (7.4 +/- 0.2 mV, tc 37.2 +/- 8.2 ms). Prolonged outward current (2 s) produced little spike frequency adaptation in either adult or newborn neurons. Onset of spike activity was not delayed by hyperpolarizing pulses preceding depolarizations. In addition, pharmacological experiments showed that HYP neurons have a tetrodotoxin-sensitive Na+ current and a delayed and an inward rectifier current but no major Ca2+ current. We conclude the following. 1) Electrophysiological membrane properties mature postnatally in HYP neurons; some of these developmental changes can be ascribed to an increase in soma size and dendritic outgrowth but others cannot. 2) Adult HYP neurons, compared with other brain stem neurons (i.e., vagal cells or cells in the nucleus tractus solitarius), are not endowed with major Ca2+ currents or K+ currents such as the A current and the Ca2(+)-activated K+ current.

Aging↗

A graphics-oriented personal computer-based microscope charting system for neuroanatomical and neurochemical studies.

This report describes a computerized microscope charting system based on the IBM personal computer or compatible. Stepping motors are used to control the movement of the microscope stage and to encode its position by hand manipulation of a joystick. Tissue section contours and the location of cells labeled with various compounds are stored by the computer, plotted at any magnification and manipulated into composites created from several charted sections. The system has many advantages: (1) it is based on an industry standardized computer that is affordable and familiar; (2) compact and commercially available stepping motor microprocessors control the stage movement. These controllers increase reliability, simplify implementation, and increase efficiency by relieving the computer of time consuming control tasks; (3) the system has an interactive graphics interface allowing the operator to view the image during data collection. Regions of the graphics display can be enlarged during the charting process to provide higher resolution and increased accuracy; (4) finally, the digitized data are stored at 0.5 micron resolution and can be routed directly to a multi-pen plotter or exported to a computer-aided design (CAD) program to generate a publication-quality montage composed of several computerized chartings. The system provides a useful tool for the acquisition and qualitative analysis of data representing stained cells or chemical markers in tissue. The modular design, together with data storage at high resolution, allows for potential analytical enhancements involving planimetric, stereologic and 3-D serial section reconstruction.

Computer Graphics↗

Repetitive firing properties of neurons in the ventral region of nucleus tractus solitarius. In vitro studies in adult and neonatal rat.

1. A brain stem slice preparation and intracellular techniques were used to examine the cellular properties of neurons within the ventral and ventrolateral region of the nucleus tractus solitarius (v-NTS) in adult and neonatal (3-12 days old) rats. These neurons are believed to be involved in the control of respiratory function. 2. On the basis of their active and passive electrophysiologic properties, cells in the v-NTS of adult rats were categorized into type A and type B neurons. Type A neurons fired spontaneously with rates ranging from 0.5 to 5 spikes/s at resting potential (-59.0 +/- 6 mV, mean +/- SD). When depolarized, type A cells responded with an initial high rate of firing, which rapidly declined to a steady state level. Spike-frequency adaptation (SFA) index (defined as steady state firing divided by peak activity x 100) was 40%, with a time constant for adaptation of 100-280 ms. When depolarized from membrane potentials more negative than resting, these neurons exhibited a silent period (up to 900 ms) before any spiking was observed (delayed excitation). The delay depended on the duration and magnitude of the hyperpolarizing prepulse that preceded depolarization. The action potentials of type A cells had a shoulder on the repolarization phase, measured 2-3 ms at one-half height, and increased in duration during repetitive firing. 3. At resting potential, type B neurons fired three to five times faster than type A. Although both type A and type B neurons showed spike-frequency adaptation, type B neurons adapted at a much faster rate than type A. The time constant for adaptation was 2-14 ms in type B cells. These cells displayed no delayed excitation on depolarization from membrane potentials more negative than rest. Some type B cells exhibited postinhibitory rebound (PIR) and depolarizing afterpotentials (DAPs). Both types A and B v-NTS neurons had comparable input resistance and showed inward rectification. 4. Neonatal v-NTS cells, in contrast to adult cells, belonged to a single population of neurons. Their resting membrane potential was -58 +/- 6.3 mV (mean +/- SD). The majority of these cells (30/34) were active (5-10 spikes/s) at rest. When depolarized, they showed an immediate increase in firing rate, which gradually slowed down to reach a steady state. Spike-frequency adaptation index was 59%, with a time constant for adaptation of 300-750 ms.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Diversity of the transient outward potassium current in somata of identified molluscan neurons.

We have undertaken a quantitative study of the differences in the properties of the fast transient outward current (A-current) between identified neurons of 2 species of nudibranch mollusc. Somata from identifiable neurons of Archidoris montereyensis and Anisodoris nobilis were isolated and voltage-clamped with a 2-microelectrode voltage clamp at 11 degrees C. We examined diversity in the expression of the time- and voltage-dependent properties of A-current by measuring the following parameters: (1) current magnitude, (2) current density, (3) inactivation kinetics, (4) the voltage dependence of steady-state activation and inactivation. We first characterized A-current in each cell type by measuring these parameters for each identified neuron in a series of animals of a given species. The results of these measurements were used to describe the A-current properties of an identified neuron in terms of a mean and SD. The SD measured diversity within the animal population for any given cell type, while the mean values could be compared to measure diversity in the expression of A-current between identified neurons. When we compared mean values for A-current properties between identified neurons of a given species, we did not detect statistically significant differences in the steady-state voltage dependence of activation and inactivation. However, there were statistically significant differences in peak A-current magnitude, density, and inactivation kinetics between identified neurons. We examined differences between the species by comparing the A-current properties of homologous neurons. The major difference between the species was that outward current magnitude and density were significantly greater in Anisodoris than in Archidoris. We conclude that the magnitude and density of A-current differ between identified nudibranch neurons. The neurons also differentially express A-current inactivation kinetics in a cell-specific manner.

Animals↗

Phrenic motor nucleus of the guinea pig: dendrites are bundled without clustering of cell somas.

In this study, the phrenic motor nucleus of adult guinea pigs was characterized following retrograde transport of horseradish peroxidase. The phrenic motor nucleus was localized to cervical sections C4-C7 in the ventromedial portion of the ventral horn. We further analyzed the internal organization of the phrenic motor nucleus by calculating the spatial interval distribution for the labeled motor neurons and their dorsally projecting dendrites which extended perpendicular to the longitudinal axis of the nucleus. Although the phrenic motor neurons were not clustered, the dendrites occurred in bundles with a mean longitudinal distance between bundles of 165 micron (range, 40-350 micron).

Animals↗

Maintenance of complex neural function during perfusion of the mammalian brain.

A perfused brain preparation was developed utilizing non-pulsatile flow of artificial blood. Cortical electrical activity and respiratory motor output were maintained for as long as 7-8 h. This preparation permits stable intracellular recordings from CNS neurons displaying ongoing respiratory activity, and should permit analysis of synaptic and intrinsic cellular mechanisms involved in producing the respiratory output. A similar approach may be useful for electrophysiology throughout the CNS, and for other fields in which control of the blood composition and/or mechanical stability are required.

Animals↗

In vitro characterization of neurons in the ventral part of the nucleus tractus solitarius. I. Identification of neuronal types and repetitive firing properties.

1. An in vitro brain stem slice preparation from adult guinea pigs was used to determine the properties of neurons located in the ventral part of the nucleus tractus solitarius (NTS), an area associated with the dorsal respiratory group. Based upon their morphology and their repetitive firing properties, three classes of ventral NTS neurons, termed types I, II, and III, were observed. 2. Type I neurons were multipolar with pyramidal-shaped cell bodies. These neurons responded to prolonged depolarizations from a resting level of -50 mV with a discrete, high-frequency burst of spikes, which rapidly adapted to a low steady-state level. When depolarized from levels more negative than -65 mV, the initial burst was diminished. 3. Type II neurons were multipolar with fusiform-shaped cell bodies. Type II neurons responded to depolarizations from -50 mV with an initial high spike frequency, which gradually adapted to a steady-state level. When depolarized from levels more negative than -60 mV, these neurons displayed a delay between the onset of the stimulus and the first spike. This delay has been termed "delayed excitation." The expression of delayed excitation was modulated by both the size and duration of hyperpolarizing prepulses that preceded depolarization. 4. Type III neurons were multipolar with spherical shaped-cell bodies. In response to depolarizations from -50 mV, these neurons displayed high-frequency firing with little adaptation. The repetitive firing properties of type III neurons were not modulated by hyperpolarization. 5. Bulbospinal neurons in the ventral NTS were identified using retrograde transport of rhodamine-labeled latex beads injected into the region of the phrenic motor nucleus at spinal cord levels C4 through C6. Only type I and type II neurons were labeled in the ventral NTS (0.2-1.0 mm rostral to the obex). Both contralateral and ipsilateral projections were observed. Contralaterally, type I and II neurons were evenly distributed. Ipsilaterally, however, type II neurons accounted for two-thirds of the labeled neurons. 6. Type I and II neurons had similar input resistances and time constants: 97.0 +/- 17.6 M omega and 14.4 +/- 2.2 ms (n = 5) for type I and 107.0 +/- 11.2 M omega and 13.7 +/- 1.6 ms for type II (n = 5).(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

In vitro characterization of neurons in the ventral part of the nucleus tractus solitarius. II. Ionic basis for repetitive firing patterns.

1. The ventral part of the nucleus tractus solitarius in guinea pigs comprises the dorsal respiratory group and is composed of three classes of neurons. These have been termed types I, II, and III. Each cell type possesses a unique set of repetitive firing properties. An in vitro brain stem slice preparation was used to study the ionic basis for these repetitive firing properties. 2. Three different membrane currents were shown to contribute to the repetitive firing properties. These were: a slow calcium current (ICa), an early, transient potassium current (IKA), and a calcium-activated potassium current (IKC). Type I and II neurons displayed physiologically significant amounts of these currents; type III neurons did not. 3. During depolarization from potential levels between -50 and -60 mV, the repetitive firing properties of type I and II neurons were determined primarily by ICa and IKC. IKA was inactivated in this potential range. The expression of IKC was greater in type I neurons than in type II neurons, and as a result, type I neurons exhibited a self-terminating burst of spike activity early in depolarization, whereas type II neurons displayed a gradual decline in spike frequency throughout depolarization. 4. The properties of IKA in type I and II neurons were studied using the single-electrode voltage-clamp technique. The kinetics of IKA in type I neurons was approximately twice as slow as those of type II neurons. In addition, the voltage dependence of activation and the removal of inactivation for IKA in type I neurons were shifted by about -10 mV with respect to type II neurons. 5. Depolarization of type I neurons from membrane potential levels where inactivation of IKA was removed caused a decrease in the frequency of the initial burst of spikes. This decrease in spike frequency was result of the coactivation of IKA with ICa. 6. Depolarization of type II neurons from membrane potentials where inactivation of IKA was removed caused a long delay between the onset of depolarization and the beginning of spike activity. The delay in excitation was modulated by both the magnitude and duration of the prestimulus hyperpolarization. This modulation of delayed excitation paralleled the time and voltage dependence for the removal of IKA inactivation in type II neurons.

4-Aminopyridine↗