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Biomedical subjects

N Dale

Publications and source records attributed to N Dale.

At least 55 records · Page 3Linked to original sources
PubMed1987

The morphology and distribution of 'Kolmer-Agduhr cells', a class of cerebrospinal-fluid-contacting neurons revealed in the frog embryo spinal cord by GABA immunocytochemistry.

An immunocytochemical method that localizes GABA in glutaraldehyde-fixed tissue has been applied to the study of the Xenopus embryo spinal cord. This procedure stained an anatomical class of neuron, which had somata forming two more or less continuous rows, one on either side of the central canal, in the ventral part of the spinal cord. The total number of stained neurons in the stage 37-38 embryo spinal cord was about 300. The medial surface on the soma protruded into the central canal and had a brush border which electron microscope studies showed to consist of many microvilli or stereocilia and one or two cilia. The external end of the neuron soma had an ipsilateral ascending axon. The axon of many of these neurons had a growth cone which was also clearly stained. We propose calling these neurons 'Kolmer-Agduhr cells' after W. Kolmer and E. Agduhr who described them in the spinal cords of many vertebrate classes. Their early embryonic origin, GABA-like immunoreactivity, axonal projections and distribution as a whole population have not previously been known.

Animals↗
PubMed1987

The development of a population of spinal cord neurons and their axonal projections revealed by GABA immunocytochemistry in frog embryos.

The development of a population of cerebrospinal-fluid-contacting neurons in the spinal cord of the Xenopus embryo ('Kolmer-Agduhr' cells) has been followed by using an immunocytochemical procedure that identifies GABA in fixed nervous tissue. Stained Kolmer-Agduhr cells containing GABA first appeared at stage 25 and their numbers increased steadily with the developmental age of the embryo. The Kolmer-Agduhr neurons had ascending ipsilateral axons that often terminated in growth cones. These axons and growth cones could be stained by the GABA antiserum from the earliest stages of outgrowth from the Kolmer-Agduhr cell body. We measured the angle of the earliest axons' outgrowth relative to the rostrocaudal axis of the spinal cord. The initial outgrowth of axons was always rostral over a narrow range of angles. This observation is inconsistent with the hypothesis of random initial outgrowth followed by later selection of the correct orientation, which would predict that axons would initially grow out over a wide range of angles. Instead, it suggests that, even from the earliest moments, axon outgrowth from the Kolmer-Agduhr cells is directed rostrally in a specific stereotyped manner.

Animals↗
PubMed1987

The early development of neurons with GABA immunoreactivity in the CNS of Xenopus laevis embryos.

We have used an antibody to glutaraldehyde fixation complexes of gamma-amino butyric acid (GABA) to stain the developing central nervous system of Xenopus laevis embryos. Neuronal somata, growth cones, axons, and dendrites were found with GABA-like immunoreactivity. Transmission electron microscope (TEM) observations were made of axons and synapses. By observation of the earliest stages of differentiation of neurons, seven classes of putative GABAergic interneurons were discerned. 1) Ascending neurons are first stained in the hindbrain at stage 26 and later extend caudally in the spinal cord. They have ascending ipsilateral axons. 2) Midhindbrain reticulospinal neurons are first stained at stage 25 and develop as a compact group with descending ipsilateral and contralateral axons. 3) Vestibular complex commissural neurons are first stained at stage 29/30 in a dorsal position near the entry of the seventh and eighth cranial nerves. They have ventral commissural axons that descend contralaterally and their somata form a compact mass. 4) Rostral hindbrain commissural neurons are first stained at stage 33/34 just rostral to the entry of the trigeminal nerve. They each have a decussating projection. 5) Rostral midbrain neurons are first stained in the midbrain at stage 29/30 and are later associated with prominent dorsal and ventral commissures. 6) Optic tract and 7) rostral forebrain neurons are found in the forebrain associated with strongly stained axon tracts. The direction of axonal growth from its earliest stages was distinct for each class of hindbrain and spinal cord neuron.

Animals↗
PubMed1987

Reticulospinal neurones activate excitatory amino acid receptors.

Paired intracellular recordings were used to study the monosynaptic excitatory postsynaptic potentials (EPSP) in lamprey motoneurones evoked by stimulation of single reticulospinal Müller and Mauthner cells. The chemical component of the synaptic potentials was depressed by both application of the non-selective excitatory amino acid antagonists kynurenic acid and cis-2,3-piperidine dicarboxylate. The N-methyl-D-aspartate (NMDA) antagonists Mg2+ and 2-amino-5-phosphonovalerate caused a selective depression of a late component of the EPSP. Thus, fast-conducting reticulospinal neurones appear to release an excitatory amino acid acting at both NMDA and non-NMDA receptors.

2-Amino-5-phosphonovalerate↗
PubMed1987

Serotonin produces long-term changes in the excitability of Aplysia sensory neurons in culture that depend on new protein synthesis.

When isolated and grown in cell culture, the sensory and motor neurons of the gill withdrawal reflex of Aplysia readily form synaptic connections. Repeated exposures to 5-HT cause facilitation of the synaptic connections between co-cultured sensory and motor neurons lasting at least 24 hr. As a first step toward understanding the locus and the mechanisms underlying this long-term synaptic facilitation, we have examined the membrane excitability of the isolated presynaptic sensory neurons grown alone in dissociated cell culture. Four repeated applications of 1 microM 5-HT caused a significant increase in the excitability of sensory neurons, lasting at least 24 hr. This resembles the short-term changes in excitability seen in response to a single application of 5-HT. Unlike the short-term effect, this long-lasting change was blocked by exposure of the cells during the 5-HT treatment to 10 microM anisomycin, an inhibitor of protein synthesis. Thus, like the synaptic facilitation, the long-term change in excitability of the isolated presynaptic neurons differs from the short-term in requiring the synthesis of new protein. This finding suggests that the sensory neuron uses gene products to modulate membrane currents in its long-term response to repeated external stimuli that are not required in its short-term response to a single stimulus.

Action Potentials↗
PubMed1986

Dual-component synaptic potentials in the lamprey mediated by excitatory amino acid receptors.

The synaptic mechanisms underlying amino acid-mediated excitation in the lamprey spinal cord have been investigated. Fine stimulating electrodes were used to stimulate single axons in the spinal cord and evoke unitary EPSPs in lamprey motoneurons and one type of premotor interneuron, the CC interneuron. Three types of EPSP, distinguished by their time course and sensitivity to amino acid antagonists, were seen. Fast EPSPs had a fast rise time (mean, 6.5 msec) and a short half-decay time (mean, 22.5 msec). Slow EPSPs lasted at least 200 msec, had a slow rise time (mean, 28 msec), and a long half-decay time (mean, 109 msec). The third type of unitary potential, called "mixed" EPSP, also lasted at least 200 msec, had a fast rise time (mean, 12 msec), and a long half-decay time (mean, 105 msec). Lamprey neurons were found to possess 3 types of excitatory amino acid receptor: N-methyl-D-aspartate (NMDA), kainate, and quisqualate receptors. 2-Amino-5-phosphonovaleric acid (APV) or Mg2+ blocked the depolarizations caused by N-methyl-D,L-aspartate (NMA) but not those of kainate or quisqualate. Cis-2, 3-piperidine dicarboxylic acid (PDA) blocked the depolarizations caused by NMA and kainate but not those of quisqualate. Fast EPSPs were unaffected by the bath application of APV or Mg2+ but were greatly reduced by PDA, suggesting that these EPSPs were mediated by non-NMDA, possibly kainate receptors. Both APV and Mg2+ blocked the slow EPSPs, suggesting that they were mediated by NMDA receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Excitatory synaptic drive for swimming mediated by amino acid receptors in the lamprey.

In order to investigate the properties and pharmacology of the excitatory synaptic drive received by motoneurons during swimming in the lamprey, propriospinal excitatory interneurons were activated as a population by the regional application of N-methyl-D,L-aspartate (NMA) to either the 6-8 rostral-most or the 6-8 caudal-most segments of lengths of isolated spinal cord. This caused a rhythmic motor output to be generated in these regions. Synaptic potentials that were phase-locked to, and dependent on, the rhythmic motor activity of the segments exposed to the agonist could be recorded in motoneurons lying outside the activated regions. The synaptic drive to motoneurons located rostral or caudal to the activated regions was studied. Motoneurons received both descending and ascending synaptic input, which consisted of alternating excitatory and inhibitory phases. The inhibition could be reversed by chloride injection and blocked by strychnine, leaving an oscillating excitatory phase. The descending excitatory drive could extend 1-9 segments from the active region, while the ascending excitatory drive was recorded only in motoneurons that were 1-3 segments rostral to the active region. Both types of drive occurred in phase with the ipsilateral ventral root discharge: The peak depolarization of the descending drive occurred at the same point in the swimming cycle as that of the depolarizing phase seen during fictive swimming, while that of the ascending drive occurred significantly later. Both ascending and descending drives were partially reduced in amplitude by 2-amino-5-phosphonovaleric acid or Mg2+. The blocking action of Mg2+ was, in both cases, voltage dependent. Cis-2,3-piperidine dicarboxylic acid or kynurenic acid caused a much greater reduction in the amplitude of the oscillations. These results suggest that a major part of the excitatory drive for swimming in lamprey motoneurons is generated by populations of propriospinal interneurons with relatively long descending and/or short ascending axons, which fire rhythmically during swimming and release an amino acid transmitter that excites motoneurons through N-methyl-D-aspartate (NMDA) and non-NMDA receptors. This information will allow these important neurons to be identified in future experiments.

Afferent Pathways↗
PubMed1985

Dual-component amino-acid-mediated synaptic potentials: excitatory drive for swimming in Xenopus embryos.

The neuronal basis of the excitation received by motoneurones during swimming in curarized Xenopus embryos has been investigated further. Extracellular stimulation of axons in the fibre tracts of the spinal cord has been used to evoke unitary excitatory post-synaptic potentials (p.s.p.s) in motoneurones. The p.s.p.s. had a rise time of 3-5 ms and a long falling phase lasting up to 200 ms. These potentials consist of two components: a 'fast' p.s.p. which is insensitive to 50 microM-(+/-)-2-amino-5-phosphonovaleric acid (APV) but is blocked by 2 mM-cis-2,3-piperidine dicarboxylic acid (PDA) and is therefore probably mediated by kainate/quisqualate receptors, and a 'slow' p.s.p. which is blocked by both APV and PDA and is therefore probably mediated by N-methyl-D-aspartate (NMDA) receptors. Paired intracellular recordings from motoneurones and interneurones have revealed a class of spinal cord interneurone which makes descending excitatory amino-acid-dependent synapses onto motoneurones and commissural interneurones. The p.s.p.s evoked by intracellular stimulation of these excitatory interneurones consist of 'fast' and 'slow' components identical in shape and pharmacological properties to those of the extracellularly evoked potentials. One neurone may, therefore, be able to release a transmitter which activates both NMDA and non-NMDA receptors on the same post-synaptic neurone generating fast and slow post-synaptic potentials. The excitatory interneurones play an important role in the generation of the swimming pattern in the curarized Xenopus embryo. Like motoneurones, they fire once per swimming cycle in phase with the ipsilateral motoneurones and receive a background excitation during swimming that is excitatory amino acid mediated. They are therefore part of the swimming rhythm generator. The temporal summation of the extracellularly evoked p.s.p.s shows that these excitatory interneurones are sufficient to generate the excitatory drive received by motoneurones during swimming.

2-Amino-5-phosphonovalerate↗
PubMed1985

Reciprocal inhibitory interneurones in the Xenopus embryo spinal cord.

The mechanism of reciprocal inhibition between antagonistic motor centres during swimming in the paralysed Xenopus embryo has been investigated further. Paired intracellular recordings have been made from interneurones and motoneurones in an attempt to identify neurones which make direct inhibitory synapses onto motoneurones on the opposite side of the spinal cord. A physiological class of inhibitory interneurones is described which, when stimulated by intracellular current passage, evoke short-latency, probably monosynaptic, strychnine-sensitive inhibitory potentials in contralateral motoneurones. These inhibitory interneurones fire once per swimming cycle in phase with the ipsilateral motor root discharge. They therefore have a pattern of activity which would cause them to inhibit motoneurones of the antagonistic motor centre at an appropriate part of the swimming cycle. The intracellular injection of horseradish peroxidase (HRP) has allowed the morphology of these inhibitory interneurones to be characterized. They have unipolar cell bodies with a thick proximal process with short dendrites which crosses the spinal cord ventrally and then bifurcates with one axonal branch ascending into the hind brain and the other descending the spinal cord. These anatomical features are typical of the 'commissural interneurones' first described by Roberts & Clarke (1982). There are also some inhibitory interneurones which can inhibit motoneurones on the same side of the spinal cord. At least some of these interneurones may be commissural interneurones with ipsilateral axons and they may play a role in the generation of the swimming rhythm.

Animals↗
PubMed1985

Synaptic potentials in motoneurons during fictive swimming in spinal Xenopus embryos.

Embryos spinalized at the 3rd to 6th postotic myotome and immobilized in 10(-4) M tubocurarine can respond to a brief skin stimulus with motor root activity suitable for swimming. Embryos spinalized at the more caudal levels give shorter episodes of fictive swimming. We have previously described the synaptic inputs to motoneurons during fictive swimming in intact embryos (23). In the present paper we look to see if similar synaptic inputs are present in spinal embryos and are therefore spinal in origin. All motoneuron firing during fictive swimming is associated with a tonic depolarization that falls away slowly once firing stops, is increased by hyperpolarizing current, and is reduced by depolarizing current. A slow depolarizing potential evoked by lower levels of skin stimulation has similar properties and rate of fall. In 1-2 mM PDA, an excitatory amino acid antagonist, only a small remnant of the depolarization remains, and motoneuron firing stops. The NMDA antagonist 50 microM APV reduces the depolarization less but also blocks firing. Motoneurons fire one spike per swimming cycle, in phase with nearby motor root discharge. Spikes are preceded by a depolarizing prepotential. This increases with hyperpolarizing current, which can block the spike to reveal an underlying depolarizing potential. In phase with motor root discharge on the opposite side of the body, motoneurons receive a midcycle inhibitory postsynaptic potential, which increases with depolarizing current, decreases with hyperpolarizing current, and is blocked by 10(-6) M strychnine. Strychnine, 5 X 10(-7) M, leads first to broadening of motor root bursts then to loss of the alternating swimming pattern of activity, which is replaced by synchronous bursts on both sides of the body. We conclude that the synaptic inputs to motoneurons during fictive swimming in spinal embryos are very similar in properties and pharmacology to those in intact embryos. These inputs, including the tonic depolarization always associated with motoneuron firing during swimming, must be at least partly spinal in origin.

Amino Acids↗
PubMed1984

Excitatory amino acid receptors in Xenopus embryo spinal cord and their role in the activation of swimming.

Bath application of N-methyl-D-aspartate (NMDA), kainate or quisqualate to Xenopus embryos depolarized spinal cord motoneurones and reduced their input resistance in both normal salines and salines containing 20 mM-Mn2+ and 0.5 mM-Ca2+, or 2 X 10(-6) M-tetrodotoxin. This suggests that motoneurones possess all three types of excitatory amino acid receptor. These receptors have similar specificities to excitatory amino acid antagonists as those occurring in adult frog and cat spinal cords. Application of 30-40 microM-NMDA or 5-6.5 microM-kainate to the medium bathing spinalized embryos can cause a sustained patterned motor output similar to that of swimming evoked by natural stimulation of intact animals. At these concentrations NMDA and kainate depolarized motoneurones by 19.0 +/- 1.80 (mean +/- S.E. of mean) and 18.0 +/- 2.00 mV respectively and decreased their input resistance by 23.0 +/- 2.82% and 24.0 +/- 3.46%. These changes are similar to those associated with the tonic excitation which motoneurones receive during naturally evoked swimming. Bath application of 5-8 microM-quisqualate to spinal embryos can also cause a sustained motor output. However, this was different to that evoked by NMDA and kainate and was inappropriate for swimming. When applied to intact animals during swimming both 2-3 mM-cis-2,3-piperidine dicarboxylic acid (PDA) and 0.5 mM-gamma-D-glutamylglycine (DGG) selectively blocked the tonic excitation of motoneurones and in doing so abolished the motor output of the spinal cord. 50-200 microM-2-amino-5-phosphonovaleric acid reduced the tonic excitation but to a lesser extent than either PDA or DGG. The tonic excitation of motoneurones which occurs during swimming therefore appears to be mediated via an endogenous excitatory amino acid transmitter which acts on NMDA and kainate receptors.

Animals↗
PubMed1984

Correlation of protein content of feedstuffs with the magnitude of nitrogen correction in true metabolizable energy determinations.

The relationship between the protein content of feedstuffs and the magnitude of difference between corresponding true metabolizable energy (TME) and nitrogen-corrected TME ( TMEn ) was investigated. Fifty-two samples of feed ingredients, mixtures of ingredients, and mixed feeds were assayed for TME and TMEn . A positive relationship was observed between the protein content of the feed samples and the magnitude of difference between determined TME and TMEn values. The regression equation describing this relationship is Y = . 122X + 3.724, where X equals percent protein and Y the percent difference between TME and TMEn . The corresponding r2 was .60.

Animal Feed↗
PubMedDate not supplied

Inhibitory neurones of a motor pattern generator in Xenopus revealed by antibodies to glycine.

Glycine and gamma-aminobutyric acid (GABA) are inhibitory transmitters of major importance. Whereas neurones using GABA as the transmitter can be visualized by immunocytochemical methods for glutamate decarboxylase (GAD) or GABA, no comparable techniques have been available for the selective visualization of glycinergic neurones. We have now produced polyclonal antibodies which specifically recognize glycine in glutaraldehyde-fixed tissue. We used these antibodies to investigate the distribution of glycine in the simple central nervous system (CNS) of the Xenopus embryo, which contains an anatomically and physiologically defined class of reciprocal inhibitory interneurones, the commissural interneurones. These interneurones have an important role in the generation of the swimming motor pattern and are thought to be glycinergic. The glycine antibodies specifically stain these interneurones, revealing their distribution and number in the embryo CNS. This is the first demonstration of the selective localization of glycine-like immunoreactivity in a putative glycinergic class of neurone that has been characterized physiologically, pharmacologically and anatomically.

Animals↗
PubMedDate not supplied

Plasticity of purine release during cerebral ischemia: clinical implications?

Adenosine is a powerful modulator of neuronal function in the mammalian central nervous system. During a variety of insults to the brain, adenosine is released in large quantities and exerts a neuroprotective influence largely via the A(1) receptor, which inhibits glutamate release and neuronal activity. Using novel enzyme-based adenosine sensors, which allow high spatial and temporal resolution recordings of adenosine release in real time, we have investigated the release of adenosine during hypoxia/ischemia in the in vitro hippocampus. Our data reveal that during the early stages of hypoxia adenosine is likely released per se and not as a precursor such as cAMP or an adenine nucleotide. In addition, repeated hypoxia results in reduced production of extracellular adenosine and this may underlie the increased vulnerability of the mammalian brain to repetitive or secondary hypoxia/ischemia.

Adenosine↗
PubMedDate not supplied

Confronting adolescent bias and intolerance through cross-cultural immersion: an American-Croatian collaboration.

This article describes a partnership to develop youth leaders and positive interventions to reverse the cycles of violence and bigotry that come when young people experience the pain and trauma of growing up in a war zone. In Croatia, Project REACH (Recreational and Educational Activities for Children's Health) serves youth who have lost their families--and their innocence--in the senseless war and "ethnic cleansing" of the former Yugoslavia. Its partner, The Children's Village (CV), provides residential treatment services for youth who have lost their families as a result of chronic abuse or neglect and who have been exposed to high levels of family and community violence in one of the most beleaguered urban areas in the United States. The partnership exposed young people from these two supposedly different parts of the world to experiences that would enable them to examine their lives, their biases, and their assumptions about the world. It was hoped that participating youth would come to see their own potential to be leaders in breaking a cycle of violence, promoting tolerance and understanding, and creating a positive effect on the world around them.

Adolescent↗
PubMedDate not supplied

Toxicological pathology of cockleburs (Xanthium spp.) for broiler chickens.

Spiking mortality syndrome (SMS) in chickens resembles cocklebur toxicity in cattle, sheep, pigs, and rats. In order to determine if cockleburs are toxic to broiler chicks, crushed burs were fed (25% wt:wt) to broilers for 21 days. Ingestion of cockleburs resulted in significant failure to properly gain body weight. Otherwise, chicks did not develop clinical signs of illness or gross or microscopic lesions. Although there were some significant differences in serum chemistry values among chick groups, there were no consistent patterns. Severe hypoglycemia is said to be a characteristic finding in chicks that die with SMS. Because glucose levels were not low in chicks that were fed cockleburs, we feel certain that cockleburs do not cause SMS.

Animal Feed↗