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Biomedical subjects

J H Wolstencroft

Publications and source records attributed to J H Wolstencroft.

At least 19 recordsLinked to original sources

Electrophysiological studies of a rostral projection from the nucleus raphe magnus to the hypothalamus in the rat and cat.

Neurones in nucleus raphe magnus (NRM) and the adjacent reticular formation with rostral projections were identified by their antidromic responses to stimulation at periventricular forebrain sites in rats and cats. In subsequent experiments, the effects of stimulation in the midline of the ventral medulla were tested on the activities of periventricular forebrain neurones. Taken together, the results of these experiments suggest that a direct inhibitory projection may exist from NRM to ventromedial forebrain structures including the anterior hypothalamus/preoptic region in rats in addition to polysynaptic pathways which mediate both excitations and inhibitions in rats and cats.

Animals↗

A microiontophoretic study of the actions of the putative sleep factor, piperidine, in the rat brainstem.

By means of microiontophoresis, we have compared the actions of a putative sleep substance, piperidine, with other neurotransmitters in the rat anaesthetized with urethane. In the pons and midbrain, piperidine mimicked the actions of acetylcholine on more than 200 neurones. Piperidine- and acetylcholine-induced excitations were equally effectively antagonized by hexamethonium or atropine. In 32 neurones piperidine showed no affinity for the receptors for the excitatory amino acid agonists, quisqualate and N-methyl-D-aspartate, piperidine-evoked excitations being unaffected by the antagonists glutamate diethylester or 2-amino-5-phosphonovalerate. Similarly, piperidine-evoked excitations in 23 neurones were unaffected by alpha-methylnoradrenaline, suggesting that piperidine does not act at receptors for noradrenaline. Twenty per cent of neurones responsive to piperidine were inhibited. These inhibitions in 12 neurones were insensitive to either strychnine or bicuculline indicating that piperidine does not act on receptors for glycine or gamma-aminobutyric acid. In a further 68 neurones, neither hexamethonium (4 out of 59 cells) nor atropine (0 out of 9 cells) was effective in antagonizing the inhibitions evoked by piperidine or by acetylcholine. It is suggested that piperidine may exert its central hypnogenic effects by an action at cholinoceptors in brainstem areas involved in sleep regulation.

Acetylcholine↗

The C-terminal dipeptide of beta-endorphin: a neuropeptide with inhibitory activity.

Glycylglutamine, the C-terminal dipeptide of beta-endorphin, has previously been shown to be present in porcine pituitary. Evidence is given that this dipeptide occurs in ovine brain stem where its concentration was shown to be similar to that of the complementary fragments of beta-endorphin determined by chromatography and radioimmunoassay. Using the technique of microiontophoresis an inhibitory activity of the dipeptide was demonstrated on neurones located in the reticular formation of rat brain stem.

Animals↗

Actions of GABA, glycine, methionine-enkephalin and beta-endorphin compared with electrical stimulation of nucleus raphe magnus on responses evoked by tooth pulp stimulation in the medial reticular formation in the cat.

In decerebrate, cerebellectomized cats, a comparison was made between the effects of electrical stimulation in nucleus raphe magnus (NRM) and iontophoretic application of GABA, glycine, met-enkephalin and beta-endorphin on the responses of neurones in the medial brain stem reticular formation to tooth pulp stimulation. NRM stimulation, GABA, glycine and enkephalin produced a short lasting inhibition of tooth pulp evoked responses whilst the time course of the inhibition produced by beta-endorphin was much slower, often lasting up to 1 h following a 3-7 min ejection period. The effects of GABA and glycine could be antagonised by iontophoresis of bicuculline and strychnine respectively whilst intravenous injection of naloxone antagonised the inhibition induced by the opioid peptides. In most neurones tested, inhibition of tooth pulp evoked responses by NRM stimulation was blocked by iontophoretic application of bicuculline but not by strychnine or naloxone (i.v.). We conclude that GABA may act as a transmitter which mediates the inhibitory effects of NRM on the responses of reticular neurones to tooth pulp stimulation. Thus GABA may be involved in stimulation produced analgesia.

Animals↗

Projections from brain stem nuclei to the spinal trigeminal nucleus in the cat.

Afferent projections to the trigeminal nucleus oralis and caudalis from the brain stem have been investigated by the use of retrograde transport of horseradish peroxidase in the cat. Both n. oralis and n. caudalis receive a projection from nucleus raphe magnus but not from other raphe nuclei in the medulla or pons. N. oralis and n. caudalis receive a bilateral projection from n. paragigantocellularis lateralis. N. oralis receives a projection from n. reticularis gigantocellularis and n. reticularis parvocellularis but not from n. reticularis magnocellularis. N. caudalis receives only sparse projections from n. reticularis gigantocellularis, n. reticularis parvocellularis and n. reticularis magnocellularis but receives an input from a layer of cells over the pyramids in the rostral medulla, here named n. paramagnocellularis ventralis. The study also revealed the presence of ascending and descending interconnections between n. oralis and n. caudalis, as well as contralateral trigeminal interconnections. Projections from the medial vestibular nuclei, n. praepositus hypoglossi and the facial nucleus to the spinal trigeminal nucleus were also noted. Since the spinal trigeminal nucleus has only sensory functions, the results indicate the source of projections, mainly from raphe and reticular nuclei, which are involved in sensory control in the trigeminal system.

Afferent Pathways↗

Strength-duration characteristics of myelinated and non-myelinated bulbospinal axons in the cat spinal cord.

Strength-duration characteristics for the stimulation of 131 raphespinal and reticulospinal axons in the spinal cord were determined using two types of stimulating electrode. Conduction velocity of these fibres ranged from 0.86 to 63 m/s. With silver wire (250 micron diameter) stimulating electrodes, chronaxies were: 0.18 +/- 0.06 ms for axons conducting between 16 and 63 m/s, 0.4 +/- 0.22 ms for axons conducting between 5 and 15 m/s and 2.06 +/- 0.79 ms for those with conduction velocity less than 5 m/s. There was an inverse relationship between chronaxie and conduction velocity. Rheobase values ranged from 7.4 to 400 microA but were independent of conduction velocity. Chronaxies obtained with wire electrodes were compared with those from stimulation of the same fibre through saline-filled micropipettes (2-12 micron tip diameter). Rheobase values with the micropipettes ranged from 1.6 to 20 microA, indicating a close proximity of the pipette to the axon. For these axons, chronaxies from metal wire electrodes ranged from 0.12 to 2.4 ms and for micropipettes from 0.04 to 0.65 ms. In almost all cases, chronaxies for micropipette stimulation were lower than those for metal wire electrodes. Furthermore, with micropipettes chronaxies were independent of conduction velocity. The results are shown to be related to differences in time constant of the activated region of axon and charge requirements of threshold activation. The two stimulating conditions, i.e. micro-electrodes compared with wire electrodes, are analogous to the theoretical point stimulated cable and uniformly polarized membrane cases. The results are discussed in relation to the possibility of determination of fibre type from stimulation characteristics. A distinction between chronaxies of myelinated and non-myelinated fibres can be made using wire electrodes of 250 micron diameter, but not with micro-stimulation, as with micropipettes (2-12 micron diameter).

Animals↗

An excitatory input to nucleus raphe magnus from the red nucleus in the cat.

In chloralose-anaesthetized cats, with the cerebellum removed, stimulation in the red nucleus excited the majority (60-65%) of neurones in nucleus raphe magnus (NRM), including raphespinal neurones. Evidence was obtained for both monosynaptic and polysynaptic excitation. The projection was confirmed by recording antidromic responses in the red nucleus to stimulation in NRM. It is suggested that the role of NRM in motor control is to inhibit spinal flexion responses to peripheral stimuli so that commands from the red nucleus and other motor control regions may take place without interruption.

Animals↗

Inhibitory actions of a novel endogenous tripeptide, methyionyl-tyrosyl-lysine, on proprioceptive neurons in the lumbar spinal cord of the cat.

The actions of a tripeptide, methionyl-tyrosyl-lysine (Met-Tyr-Lys), isolated from spinal cord and dorsal root ganglia have been investigated by iontophoretic application to single neurones in the spinal cord of the cat. Met-Tyr-Lys inhibited a group of neurons located mainly in laminae V and VI of the lumbar dorsal horn: excitation was never observed. The inhibition was rapid in onset and was not mimicked by the action of the constituent amino acids. Neurons inhibited by Met-Tyr-Lys received proprioceptive inputs as shown by their excitation or inhibition from stimulation of deep receptors and by their responses to leg or foot movement. Bicuculline and strychnine separately, at doses which antagonized responses to gamma-aminobutyric acid and glycine, respectively, had no or little effect both on responses to Met-Tyr-Lys and on the inhibition evoked in the same neurons by low-intensity (1.5-4T) stimulation of the tibial or common peroneal nerves. Thus receptors for Met-Tyr-Lys are different from those for glycine or gamma-aminobutyrate. In addition it is possible that there is a component of the inhibition evoked by peripheral nerve stimulation which is not mediated by either glycine or gamma-aminobutyrate. Met-Tyr-Lys may have an inhibitory role in relation to proprioception.

Animals↗

Effects of methionyl-tyrosyl-lysine on neurones in the rat central nervous system.

1 The effects of microiontophoretically applied methionyl-tyrosyl-lysine (Met-Tyr-Lys) were studied on single neurones in several brain regions of rats anaesthetized with urethane. 2 Met-Tyr-Lys inhibited 13.5%-25% of neurones in the spinal cord, cerebellar cortex, thalamus and hippocampal formation. No significant inhibitory effects were seen in the cerebral cortex. 3 Additionally, Met-Tyr-Lys excited some cells in the Purkinje cell body layer of the cerebellar cortex (11%) and in the pyramidal cell body layer of the hippocampus and granule cell body layer of the dentate gyrus within the hippocampal formation (17.5%). 4 Both excitatory and inhibitory effects of Met-Tyr-Lys were dose-dependent, of similar rapid time course and were observed both on spontaneously active cells and cells induced to fire by continuous iontophoretic application of DL-homocysteic acid. 5 The possibility that Met-Tyr-Lys might be a novel inhibitory neurotransmitter in both spinal and supraspinal regions of the mammalian CNS is discussed.

Animals↗

Inhibition from nucleus raphe magnus of tooth pulp responses in medial reticular neurones of the cat can be antagonized by bicuculline.

In decerebrate cats stimulation in nucleus raphe magnus (NRM) inhibited the response of neurones in the medial brain stem reticular formation to electrical stimulation of the tooth pulp. These evoked responses were also reduced by iontophoretically applied GABA. The inhibition from NRM was blocked by bicuculline applied by iontophoresis in 10 out of 16 neurones and the actions of GABA were also antagonized. Inhibition following stimulation in the contralateral reticular formation was not blocked by bicuculline. The results suggest that GABA is involved as a neurotransmitter in mediating the effects of NRM stimulation on reticular neurones.

Animals↗