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F M Clark

Publications and source records attributed to F M Clark.

10 recordsLinked to original sources
PubMed1993

The projections of noradrenergic neurons in the A5 catecholamine cell group to the spinal cord in the rat: anatomical evidence that A5 neurons modulate nociception.

Brainstem noradrenergic neurons located in the A5, A6, and A7 catecholamine cell groups provide the entire noradrenergic innervation of the spinal cord. We have previously demonstrated that noradrenergic neurons in the A6 and A7 cell groups innervate the ventral and dorsal horns, respectively. Since the specific spinal cord terminations of the A5 cell group have not been clearly delineated, the present experiments were designed to trace the projections from this noradrenergic cell group to the spinal cord, using the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHA-L) in combination with dopamine-beta-hydroxylase immunocytochemistry. The results of these experiments indicate that A5 noradrenergic neurons project ipsilaterally through the dorsolateral funiculus in cervical, thoracic, and lumbar segments. In cervical segments, these axons terminate primarily in the ipsilateral deep dorsal horn (laminae IV-VI) and the intermediate zone (lamina VII). In thoracic segments, the intermediolateral cell column is heavily innervated by A5 axons. In lumbar segments, the concentration of A5 axons is more diffuse and more widely distributed than that in cervical and thoracic segments. Although there is a higher density of axons in the deep dorsal horn and the intermediate zone, there are also scattered axons in the dorsal and ventral horns. The innervation of these regions of the spinal cord by A5 neurons provides anatomical support for the conclusion that these noradrenergic neurons are involved in modulating cardiovascular reflexes and nociceptive transmission in the spinal cord.

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PubMed1992

Anatomical evidence for genetic differences in the innervation of the rat spinal cord by noradrenergic locus coeruleus neurons.

Pontospinal noradrenergic neurons located in the A5, A6 (locus coeruleus, LC), and A7 cell groups are the major source of the noradrenergic innervation of the spinal cord. We have recently examined the specific terminations of these three cell groups in the spinal cord and found that the LC provides the major noradrenergic innervation of the ventral horn, while the A7 and A5 cell groups innervate the dorsal horn and intermediate zone, respectively. However, the results of similar experiments from another laboratory have shown that noradrenergic neurons in the locus coeruleus primarily innervate the dorsal horn, while the A5 and A7 innervate the intermediate zone and the ventral horn. These conflicting results may be due to fundamental genetic differences between the rats used in our experiments (Sasco Sprague-Dawley) and those used by the other laboratory (Harlan Sprague-Dawley). This possibility was examined by determining the projections of coeruleospinal neurons in these two rat substrains using the anterograde tracer Phaseolus vulgaris leucoagglutinin. The results indicate that in Sasco rats the LC neurons project through the ipsilateral ventromedial funiculus and terminate almost exclusively in the medial part of laminae VII and VIII, the motoneuron pool of lamina IX, and lamina X. In contrast, LC neurons in Harlan rats project bilaterally through the superficial dorsal horn and the dorsolateral funiculus and terminate most heavily in dorsal horn laminae I-IV. In addition, the LC neurons of Sasco rats innervate cervical spinal cord segments more densely than lumbar spinal cord segments, while in Harlan rats the lumbar spinal cord is more densely innervated than the cervical spinal cord. These results indicate that the projections of coeruleospinal neurons in Sasco rats are fundamentally different from those in Harlan rats and suggest that noradrenergic LC neurons may have different physiological functions in these two rat substrains.

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PubMed1991

The projection of noradrenergic neurons in the A7 catecholamine cell group to the spinal cord in the rat demonstrated by anterograde tracing combined with immunocytochemistry.

Noradrenergic neurons located in the A5, A7 and locus coeruleus/subcoeruleus (LC/SC) catecholamine cell groups innervate all levels of the spinal cord. However, the specific spinal cord terminations of these neurons have not been clearly delineated. This study determined the spinal cord terminations of the A7 catecholamine cell group using the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L) in combination with dopamine-beta-hydroxylase (DBH) immunocytochemistry. In addition, the spinal cord projections of A7 neurons were examined by measuring the reduction in the density of DBH-immunoreactive axons in specific regions of the spinal cord after a unilateral electrolytic lesion of the A7 cell group. The results of these experiments indicate that noradrenergic neurons in the A7 cell group project primarily in the ipsilateral dorsolateral funiculus and terminate most heavily in the dorsal horn (laminae I-IV).

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PubMed1991

The noradrenergic innervation of the spinal cord: differences between two substrains of Sprague-Dawley rats determined using retrograde tracers combined with immunocytochemistry.

We have recently described the spinal cord terminations of noradrenergic neurons located in the A5, A6 and A7 cell groups. However, recent reports from another laboratory, using similar experimental methods, have described results that are profoundly different. The present experiments were designed to determine whether these discrepant results are due to fundamental differences between the substrains of rats used in the conflicting experiments. To this end, retrograde tract tracing experiments were done using Sprague-Dawley rats from either Sasco, Inc. or Harlan Sprague-Dawley, Inc. The results indicate that noradrenergic neurons in the pontine catecholamine cell groups exhibit remarkably different spinal cord projections in these two substrains of Sprague-Dawley derived rats.

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PubMed1991

Projections of neurons in the ventromedial medulla to pontine catecholamine cell groups involved in the modulation of nociception.

Stimulation of neurons in the nucleus raphe magnus (RMg) or the adjacent gigantocellular nucleus pars alpha (Gi alpha) and paragigantocellular nucleus (PGi) produces antinociception which is partially mediated by bulbospinal noradrenergic neurons. Since no norepinephrine-containing neurons are located in either the RMg or the Gi alpha/PGi, it is likely that neurons located in these nuclei have axonal connections with the spinally-projecting catecholamine neurons located in the A5, A6 (locus coeruleus), or A7 catecholamine cell groups. To provide evidence for such connections, the anterograde tracer, Phaseolus vulgaris-leucoagglutinin (PHA-L), was injected into the RMg or Gi alpha/PGi and labeled axons were identified near catecholamine-containing neurons labeled with dopamine-beta-hydroxylase-immunoreactivity (D beta H-ir). A dense field of PHA-L-positive terminals was seen within the A7 cell group which was mainly ipsilateral to PHA-L injections made into either the RMg or the Gi alpha/PGi. Many PHA-L-positive terminals were closely apposed to D beta H-ir A7 perikarya or proximal dendrites. A modest number of terminals was seen within the A5 and LC cell groups. In the second experiment, a unilateral injection of the retrograde tracer, Fluoro-Gold, was made into the A7 cell group and brainstem sections were processed for serotonin (5-HT) immunocytochemistry. Many neurons retrogradely labeled with Fluoro-Gold were seen in the RMg, but a much larger number were found in the Gi alpha/PGi. Less than 5% of these Fluoro-Gold-labeled cells contained 5-HT-immunoreactivity. The results of these experiments indicate that the RMg and Gi alpha/PGi have a substantial population of non-serotonergic neurons which project to the A7 noradrenergic cell group.

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PubMed1991

The projection of locus coeruleus neurons to the spinal cord in the rat determined by anterograde tracing combined with immunocytochemistry.

Pontospinal noradrenergic neurons located in the A5, A7 and locus coeruleus/subcoeruleus (LC/SC) nuclei are the major source of the noradrenergic innervation of the spinal cord. However, the specific terminations of spinally-projecting noradrenergic neurons located in these nuclei have not been clearly defined. The purpose of the experiments described in this report was to more precisely define the spinal terminations of neurons located in the LC/SC using the anterograde tracer phaseolus vulgaris-leucoagglutinin in combination with dopamine-beta-hydroxylase (D beta H) immunocytochemistry. In addition, the spinal cord regions in which LC/SC neurons terminate was assessed by measuring the reduction in the density of D beta H-immunoreactive axon terminals in specific spinal cord regions after a unilateral electrolytic lesion that included LC/SC neurons. The results of these experiments indicate that the axons of LC neurons are located primarily in the ipsilateral ventral funiculus and terminate most heavily in the medial part of laminae VII and VIII, the motoneuron pool of lamina IX, and lamina X. LC neurons provide a moderately dense innervation of the ventral part of the dorsal horn, but only a very sparse innervation of the superficial dorsal horn. The SC projects ipsilaterally in the ventrolateral funiculus and terminates diffusely in the intermediate and ventral laminae of the spinal cord.

Animals↗
PubMed1991

The projections of locus coeruleus neurons to the spinal cord.

Spinally projecting noradrenergic neurons located in the locus coeruleus/subcoeruleus (LC/SC) are a major source of the noradrenergic innervation of the spinal cord. However, the specific terminations of these neurons have not been clearly defined. The purpose of this chapter is to describe the results of experiments that used the anterograde tracer Phaseolus vulgaris leucoagglutinin in combination with dopamine-beta-hydroxylase immunocytochemistry to more precisely determine the spinal cord terminations of neurons located in the LC/SC. The results of these experiments indicate that the axons of LC neurons are located primarily in the ipsilateral ventral funiculus and terminate most heavily in the medial part of laminae VII and VIII, the motoneuron pool of lamina IX, and lamina X. LC neurons provide a moderately dense innervation of the ventral part of the dorsal horn, but only a very sparse innervation of the superficial dorsal horn. The SC projects ipsilaterally in the ventrolateral funiculus and terminates diffusely in the intermediate and ventral laminae of the spinal cord. Finally, the results of preliminary experiments indicate that different rat substrains may have LC neurons that exhibit qualitatively different termination patterns in the spinal cord. More specifically, LC neurons in some rat substrains innervate the dorsal horn, while those in other substrains primarily innervate the ventral horn and intermediate zone.

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PubMed1988

An inexpensive sleep-wake state analyzer for the rat.

Manual classification of sleep stages is a tedious and time consuming task. We describe an inexpensive system for sleep-wake state classification for as many as eight rats at a time. It is based on determining threshold values for each parameter of each rat, then finding the natural transitions from one sleep state to another and finally classifying these states utilizing the cortical EEG and EMG signals.

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PubMed1988

A low-priced computer-assisted densitometer and analysis software for quantitative autoradiography.

A computer-assisted densitometer which consists of a darkroom enlarger, a black-and-white exposure meter, an amplifier, an analog-to-digital converter, and a microcomputer with a monitor and a graphic printer can be utilized for the quantitative analysis of autoradiograms. QUANTAR, a computer program written in BASIC, records the density measurements and stores the data in a file that can be easily retrieved by commercially available spreadsheet software. A spreadsheet template was designed to convert the digital readings into concentration of ligand in tissue. A variety of spreadsheet templates can be created to analyze data for a standard curve, a Scatchard plot, or a binding competition curve. This system, which is easy to assemble, may be useful to the frugal investigator with a modest equipment budget.

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