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D W Walker

Publications and source records attributed to D W Walker.

At least 145 records · Page 8Linked to original sources

Effects of hypoxia on polysynaptic hind-limb reflexes in new-born lambs before and after carotid denervation.

Polysynaptic reflex responses in the hind limb were obtained by stimulating the peroneal nerve in unanaesthetized lambs between 4 and 12 days from birth, before and after carotid denervation. In intact lambs isocapnic reduction of the Pa,O2 from 88 to 31 or to 23 mmHg caused an insignificant decrease in reflex amplitude. Denervation of the carotid bifurcations induced hypoventilation. When the Pa,O2 was then reduced to 22 mmHg the reflex amplitude fell by 77%. In carotid denervated lambs after complete transection of the spinal cord at T12-L1, reduction of the Pa,O2 to 23 mmHg did not alter the size of the reflex. The same result was observed after section of the dorsal part of the lateral funiculi. It is concluded that, in the young lamb a few days after birth, the afferent activity of the carotid chemoreceptors during hypoxia plays an important role in maintaining the excitability of motor reflexes. The possible mechanisms are discussed.

Animals↗

Changes in breathing, electrocortical and muscle activity in unanaesthetized fetal lambs with age.

Electrocortical and electro-ocular activity, breathing movements and nuchal muscle activity were recorded continuously in the unanaesthetized lamb in utero (95-135 days). Electrocortical activity was recorded simultaneously from various sites. The bi-parietal electrocorticogram gave the clearest differentiation between high- and low-voltage activity. The onset of cortical differentiation from 110 days gestation was attributed to the superimposition of high-voltage electrocortical activity at 3-10 Hz on existing low-voltage activity. Three distinct patterns in the relationships between electrocortical activity, ocular activity breathing movements and nuchal muscle activity were observed at 95-106, 107-114 and 120-135 days. Isocapnic hypoxia caused a diminution in fetal breathing from 95-135 days gestation, quantitatively greater near term. After cortical differentiation, hypoxia caused the appearance of high-voltage activity within 4 min, if low-voltage electrocortical activity was present initially. The relationship, changing with age, between electrocortical activity, breathing movements, ocular and nuchal muscle activity is discussed.

Action Potentials↗

Electrophysiological analysis of synaptic distribution in CA1 of rat hippocampus after chronic ethanol exposure.

This study investigated the long-lasting effects of chronic ethanol consumption on the distribution of Schaffer collateral-commissural (SCH/COM) afferents within stratum radiatum of rat hippocampal CA1. Experimental animals were fed an ethanol-containing liquid diet for 20 weeks but were withdrawn from the special diet for at least 8 weeks prior to acute electrophysiological recordings. Field potential laminar analyses were performed by stepping the recording electrode in 25 microns increments through CA1 and sampling evoked potentials at each point. One-dimensional current-source density (CSD) was calculated from the field potential laminar profiles to enhance spatial resolution of current sources and sinks. Stimulation of the SCH/COM afferents elicits short-latency, negative field potentials throughout the synaptic terminal zone (stratum radiatum). CSD analysis in normal animals revealed that the synaptic currents generated in stratum radiatum concentrate into bimodal yet overlapping components, peaking 71.3 microns and 228.3 microns from the pyramidal cell layer. Chronic ethanol treatment produced: (1) a 13.2% shrinkage of the overall extent of current sinks in stratum radiatum; (2) a 37.4% reduction in the spatial extent of the sink proximal to the cell layer; and (3) an increase in the amplitude of the more distal sink. We tentatively propose the proximal and distal sinks to reflect a separation of the COM and SCH afferents, respectively. Chronic ethanol thus appeared to have selectively produced persistent damage to the COM-CA1 pathway.

Action Potentials↗

Effects of hypercapnia on tracheal pressure, diaphragm and intercostal electromyograms in unanaesthetized fetal lambs.

1. The electromyographic (e.m.g.) activity of the diaphragm and intercostal muscles has been recorded during breathing movements of unanaesthetized lambs in utero (109-135 days), and compared with the changes of tracheal pressure.2. The diaphragm e.m.g. was irregular in size, shape and timing, with a variable rate of rise during inspiration, often with a flattening of integrated activity before the end of a breath and with little or no post-inspiratory activity.3. The diaphragm e.m.g. gave the most reliable measurements of breath interval and incidence: in eucapnia mean T(I) was 0.45+/-0.02 (S.E. of mean) and T(E) was 0.74+/-0.05 sec, and 58-100% of the diaphragm bursts were associated with identifiable and appropriate changes of tracheal pressure.4. During fetal hypercapnia, produced by increasing the maternal inspired CO(2) in a single change or series of step changes, tracheal pressure amplitude and its rate of change during inspiration increased progressively over the P(a, CO2) range of 37-87 mmHg.5. In eucapnia the area, amplitude and inspiratory slope of the integrated diaphragm e.m.g. were not always correlated with tracheal pressure amplitude, and in hypercapnia they increased only in the lower part of the P(a, CO2) range. Inspiratory intercostal activity increased progressively as the P(a, CO2) was raised.6. The frequency histograms of variables derived from the tracheal pressure, diaphragm and intercostal e.m.g.s were skewed to the left in eucapnia but became normalized during hypercapnia. The rate and depth of breathing became regular.7. The response to mild asphyxia was a combination of the responses to hypercapnia and hypoxia.8. The interpretation of the tracheal pressure and diaphragm e.m.g. as measures of the ;depth' of breathing and respiratory ;drive' in the fetal lamb is discussed.

Animals↗

The response to stimulation of hindlimb nerves in fetal sheep, in utero, during the different phases of electrocortical activity.

The relationship between the amplitude of electrically evoked responses from nerves of a hindlimb and electrocortical activity has been determined in fetal sheep from 105-141 days gestation. Stimulation of the common sciatic, tibial or peroneal nerves and recording from the two nerves not stimulated revealed an early (4.5 ms) and late (18.6 ms) evoked neural response, probably reflex. These responses were reduced or absent in low voltage compared with high voltage electrocortical activity after 125 days gestation. Spontaneous gastrocnemius activity was more frequent during high voltage activity. The electrocorticogram was undifferentiated before 115 days, and the evoked responses in peripheral nerves were largest when breathing and eye movements were present. After electrocortical differentiation the responses were enhanced when brief episodes of augmented eye and breathing movements occurred during the transition between high and low voltage activity. The possibility that this indicates arousal or wakefulness in utero is discussed.

Animals↗

Augmentation of short-term plasticity in CA1 of rat hippocampus after chronic ethanol treatment.

The neurotoxic effects of chronic ethanol exposure were investigated in rat hippocampus by electrophysiological analysis of the Schaffer collateral-commissural input to stratum radiatum of CA1. Experimental animals were fed an ethanol-containing liquid diet for 20 weeks but were withdrawn from the special diet at least eight weeks prior to acute electrophysiological recordings. Ethanol treatment had no effect on input-output relationships for either the population EPSP or the population spike (PS). During paired-pulse stimulation, the ethanol group exhibited a greater facilitation of the test pulse PS relative to the control group, although potentiation of the EPSP was unchanged. In addition, the ethanol group showed a trend toward greater facilitation of the PS during 5 and 10 Hz tetani. No differences between groups were observed in the magnitude or duration of the long-term potentiation produced by 5, 10 or 100 Hz stimulus trains. Ethanol treatment did significantly reduce the transient spike depression after low frequency stimulation. This pattern of results is similar to that found for treatments which reduce hippocampal recurrent inhibition. Thus, chronic ethanol treatment may produce a lasting disruption of intrinsic inhibitory neurotransmission in the rat hippocampus.

Animals↗

The central control of fetal breathing and movements.

In fetal lambs after 115 days gestation breathing movements become episodic in association with electrocortical differentiation into predominantly high voltage slow or low voltage rapid activity, the latter characteristic of rapid eye movement sleep. Section of the brainstem at or above the colliculi dissociates fetal breathing from electrocortical activity. It is included that breathing is inhibited, towards the end of gestation, by a supracollicular mechanism during high voltage activity. After brainstem transection at the colliculi hypoxia no longer causes an arrest of fetal breathing, which often becomes more vigorous. The arrest of breathing in normal fetuses subjected to mild hypoxia is also attributed to a supracollicular mechanism. The pattern of fetal skeletal movements and of the spinal segmental reflexes is related to electrocortical activity near term; both are suppressed by hypoxia. The hypothesis is discussed of a central control centre, excited directly or indirectly by hypoxia, which inhibits fetal movements including breathing. Its possible location is considered.

Animals↗

Prenatal ethanol exposure permanently reduces the number of pyramidal neurons in rat hippocampus.

The effect of prenatal ethanol exposure in the rat on the development of dorsal hippocampal pyramidal and dentate gyrus granule cells was examined. Ethanol was administered in a nutritionally adequate liquid diet to pregnant rats during days 10--21 of gestation. Control groups were either pair-fed the same liquid diet, except for equicaloric substitution of sucrose for ethanol, or received free access to pelleted laboratory food. The brains of 60-day-old offspring exposed to ethanol during gestation were found to have 20% fewer dorsal hippocampal pyramidal cells than did those of controls. Prenatal ethanol exposure, however, did not affect the number of dentate gyrus granule cells. Prenatal exposure to ethanol permanently reduced the number of prenatally formed hippocampal neurons without altering physical growth, which suggested that the developing nervous system is particularly sensitive to the toxic effects of ethanol.

Alcohol Drinking↗

Neuronal loss in hippocampus induced by prolonged ethanol consumption in rats.

Quantitative neurohistological techniques were used to examine the hippocampal complex of laboratory rats maintained on ethanol-containing or control diets for 5 months followed by a 2-month alcohol-free period. Chronic ethanol consumption resulted in a significant loss of hippocampal pyramidal and dentate gyrus granule cells. This study provides direct evidence that long-term ethanol consumption, in the absence of malnutrition, produces neuronal loss in the central nervous system.

Animals↗

Chest wall movements during fetal breathing in the sheep.

1. Movement of the chest wall and abdomen during episodes of breathing has been measured by an ultrasound technique in ten fetal lambs. 2. The fetal thoracic and abdominal walls move inwards and outwards respectively during inspiration. The position where this transition occurs is variable. 3. Movement of the lateral thoracic walls is reduced or reversed during breathing stimulated by hypercapnia while inward dorso-ventral movement increases. 4. Deep inspiratory efforts were associated with large inward then outward movements of the lateral and large inward movements of the dorso-ventral thoracic walls. 5. No relationship was found between the amplitude of the tracheal pressure deflexions and the extent of thoracic wall movements during fetal breathing.

Abdominal Muscles↗

Relationship of arterial pressure and heart rate in fetal, new-born and adult sheep.

1. Baroreflex activity was assessed in nine fetal, four new-born and six adult sheep, using the relationship between heart period and arterial pressure. Arterial pressure was raised either by inflating a balloon in the dorsal aorta, by rapid intravenous injection of phenylephrine or methoxamine, or by slow intravenous infusion of methoxamine. 2. In the fetus the three methods gave different estimates of baroreflex sensitivity (balloon, 1.3 +/- 0.7 mmHg; injections, 5.4 +/- 0.5 msec mmHg; infusions, 7.2 +/- 0.9 msec/mmHg) whereas they were comparable in the new-born and adult. 3. Estimates of baroreflex sensitivity were significantly lower in the fetus and new-born than in the adult whichever method was used. 4. In the fetus there were variable changes of heart period when arterial pressure was raised by inflation of the balloon. The responses to injection of phenylephrine or methoxamine were also variable. 5. This variability was not associated with changes in electrocortical activity, the presence or absence of breathing movements or limb movements, or changes of blood gases. 6. In the fetus the heart period frequently did not change unless the arterial pressure was raised by approximately 15 mmHg (to 61 mmHg), suggesting that the threshold for baroreflex activity is above the normal range of arterial pressure before birth.

Animals↗

Prostaglandins in the umbilical and uterine circulations during late pregnancy in the ewe.

Prostaglandins (PG) E and F, and 13,14-dihydro-15-keto-prostaglandin F (PGFM) were measured in plasma collected from the umbilical artery and vein, the maternal carotid artery, and the utero-ovarian vein of pregnant sheep between 116 and 139 days of gestation. PGE levels were greater than PGF levels in the umbilical artery and vein and the maternal carotid artery, but not in the utero-ovarian vein. PGFM exceeded PGF in samples from all vessels. There was a significant vein-to-artery concentration difference for PGF and PGFM, but not for PGE, in the umbilical circulation. Utero-ovarian concentrations of all 3 PGs generally exceeded their concentrations in the maternal caroitd artery.

Animals↗

Morphological alterations in hippocampus after long-term alcohol consumption in mice.

Golgi methods were used to examine the hippocampus of laboratory mice that received alcohol-containing or control diets for 4 months followed by a 2-month alcohol-free period. Long-term alcohol consumption resulted in a significant loss of dendritic spines on hippocampal pyramidal cells and dentate granule cells. This study provides evidence that long-term alcohol consumption, in the absence of malnutrition, produces morphological damage to the central nervous system.

Alcoholism↗

Ethanol dependence in the rat: temporal changes in neuroexcitability following withdrawal.

Electrodes were chronically implanted in the dorsal hippocampus of rats. Pretreatment levels of neural excitability were assessed by determining the duration of direct hippocampal electrical stimulation sufficient to induce forelimb clonus in each rat. Following baseline measurements the rats were administered an alcohol or sucrose-containing liquid diet and 19--22 days later were withdrawan. Two postwithdrawal stimulation sessions were conducted on each animal. Separate groups of ethanol-dependent and control rats were given primary stimulation sessions at 8 h, 24 h, 72 h, or 1 week postwithdrawal. Secondary stimulation sessions were conducted 1 week or 2 weeks postwithdrawal. The results from the primary stimulations indicated that ethanol-dependent animals exhibited significant neural hyperexcitability for at least 72 h, but not 1 week, postwithdrawal. Results from the secondary stimulations demonstrated the presence of a relative neural hypoexcitability in ethanol-dependent groups as compared to controls. The pattern of results suggests, however, that the observed relative neural hypoexcitability was not the direct result of ethanol withdrawal.

Alcoholism↗