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M H Roberts

Publications and source records attributed to M H Roberts.

At least 37 records · Page 2Linked to original sources
PubMed1995

Direct projections from the anterior pretectal nucleus to the ventral medulla oblongata in rats.

The anterior pretectal nucleus has recently been implicated in the descending modulation of nociception. Electrical stimulation of the nucleus was found to reduce the nociceptive responses of deep dorsal horn neurons and to inhibit spinally integrated withdrawal reflexes. It is believed that at least part of the descending inhibitory effects of the anterior pretectal nucleus are mediated by reticulospinal cells of the ventrolateral medulla. The purpose of the present study was to trace the direct medullary projections of the anterior pretectal nucleus, to describe their topographical organization and to reveal the chemical nature of some of their putative target cells. The connections were studied using anterograde tract-tracing with Phaseolus vulgaris leucoagglutinin. Direct projections from the anterior pretectal nucleus to the ipsilateral rostral ventral medulla were found in all cases. A dense innervation of the dorsal inferior olive, the gigantocellular reticular nucleus pars ventralis and pars alpha and the ventral pontine reticular nucleus was found from all aspects of the anterior pretectal nucleus. Descending labelled terminals were also observed in the gigantocellular reticular nucleus proper and, laterally, in the lateral paragigantocellular nucleus and in the region of the A5 noradrenergic cell group. A relatively lower density of labelled terminals was noted in the medullary raphe nuclei and in the rostroventrolateral reticular nucleus. Following tract-tracer injections into five distinct subregions of the anterior pretectal nucleus, the topographical organization of the projection was examined and the relatively highest density and most widespread projection was found to originate from the caudoventral part of the anterior pretectal nucleus. A combined tract-tracing and immunolabelling study revealed that some of the descending, labelled terminals were in close proximity of tyrosine hydroxylase-immunoreactive dendrites in the C1 and A5 cell groups. Some labelled fibres were also noted among the serotonin-immunoreactive cells in the lateral extension of the B3 cell population. The existence of direct projections to the ventral medulla and pons correlates well with physiological data which showed that the descending, antinociceptive effects of the anterior pretectal nucleus are relayed via the rostral ventrolateral medulla. The data are also in keeping with pharmacological studies that suggested the role of catecholaminergic cells in the mediation of these descending effects. It is proposed that the rostral ventral medullary projections provide a path through which antinociceptive effects of the anterior pretectal nucleus are mediated to the spinal cord.

Animals↗
PubMed1994

Identification of CDK- and cyclin-like proteins in the eye of Bulla gouldiana.

The ocular circadian rhythm in the eye of Bulla gouldiana is generated by a rhythm in membrane potential of retinal neurons that is driven by alterations in potassium conductance. Since potassium conductance may be modulated by the phosphorylation of potassium channels, the circadian rhythm may reflect rhythmic changes in protein kinase activity. Furthermore, the circadian rhythm recorded from the Bulla eye can be phase shifted by agents that affect protein synthesis and protein phosphorylation on tyrosine residues. Interestingly, the eukaryotic cell division cycle is generated by similar processes. Rhythmic cell division is regulated by periodic synthesis and degradation of a protein, cyclin, and periodic tyrosine phosphorylation of a cyclin-dependent kinase (cdk), p34cdc2. The interaction between these two proteins results in rhythmic kinase activity of p34cdc2. Both cyclin and p34cdc2 are part of two diverse gene families, some of whose members have been localized to post-mitotic cell types with no function yet determined. In the current work, we identify proteins similar to the cdks and cyclin in the eye of Bulla. Neither of these ocular proteins are found in mitotic cells in Bulla, and the cdk-like protein (p40) is specific to the eye. Furthermore, the concentration of the cyclin-like protein (p66) is affected by treatments that phase shift the circadian rhythm. The identification of cdk and cyclin-like proteins in the Bulla eye is consistent with the hypothesis that the biochemical mechanism responsible for generating the ocular circadian rhythm in Bulla is related to the biochemical mechanism that regulates the eukaryotic cell division cycle.

Animals↗
PubMed1992

The pontine parabrachial region mediates some of the descending inhibitory effects of stimulating the anterior pretectal nucleus.

Electrical stimulation of the anterior pretectal nucleus (APtN) elicits antinociception by inhibiting the responses of spinal multireceptive neurones to noxious stimuli. This descending inhibition is mediated, in part, by activating cells in the ventrolateral medulla. Neuronal tract tracing has previously shown that the APtN also projects directly to the pontine parabrachial region (PPR). The PPR, investigated by Katayama et al. (Brain Res., 296 (1984) 263-283), corresponds to the cholinergic cell group Ch5 of Mesulam et al. (Neuroscience, 10 (1983) 1185-1201). In this study, the pathway from APtN to PPR was investigated using urethane anaesthetised rats. Electrical stimulation (single square wave 0.2 ms pulses, 1-10 V, 5 Hz) of the APtN potently excites 40% of the cells recorded in the PPR. In the reverse experiment, stimulation of the PPR at the same parameters excited 36% of the cells recorded in the APtN. The contribution of this pathway to the spinal inhibitory effects of APtN stimulation was then examined. Unanaesthetised animals received electrical stimulation to the APtN (35 microA r.m.s., 15 s) and the increase in tail-flick latencies was measured. Bilateral electrolytic lesions of the PPR caused a 67% reduction of the antinociceptive effect of APtN stimulation. In urethane anaesthetised rats, microinjection of tetracaine into the PPR blocked the inhibition of multireceptive dorsal horn neurones caused by APtN stimulation (20 s train of 50 microA square wave 0.1 ms pulses, 100 Hz). In conclusion, these experiments strongly sugget that the PPR may be an important part of a descending antinociceptive pathway originating in the APtN.

Animals↗
PubMed1992

Tyrosine kinase regulation of a molluscan circadian clock.

On a formal level the clocks regulating circadian and cell division cycles are related in that both have been modeled as limit cycle oscillations (Science, 211 (1981) 1002-1013; Brain Res., 504 (1989) 211-215; Proc. Natl. Acad. Sci. USA, 88 (1991) 7328-7332). Furthermore, in several organisms each clock system is able to modulate the other (Science, 211 (1981) 1002-1013). However, in spite of the similarities at the formal level, and the connections at the physiological level, no common cellular elements have been identified linking the two processes. In the current series of experiments we show that one key element of cell cycle regulation, tyrosine phosphorylation/dephosphorylation is intimately associated with circadian rhythm generation in the eye of the marine snail, Bulla gouldiana. The importance of tyrosine kinase activity in the generation of circadian rhythms provides a possible point of similarity between the fundamental biochemical mechanisms underlying both circadian and cell cycle clocks.

Animals↗
PubMed1992

A post-synaptic depressant modulatory action of 5-hydroxytryptamine on excitatory amino acid responses in rat entorhinal cortex in vitro.

The depressant action of 5-hydroxytryptamine (5-HT) in slices of entorhinal cortex of the rat has been examined. When single intracellular recordings of pyramidal cells in layers II/III of entorhinal cortex of the rat were made and drugs applied by iontophoresis, 5-HT evoked virtually no changes in passive membrane properties of the majority of cells studied. When short regular pulses of glutamate were applied to the neurones and 5-HT was ejected in addition, the depolarisations caused by glutamate were considerably reduced in amplitude. This attenuation persisted in medium containing cadmium chloride (200 microM) to block synaptic transmission. The magnitude of the response to 5-HT was dependent on the ejection current and this effect could not be mimicked by increasing ejections of Na+ or H+ ions. 5-Hydroxytryptamine had no apparent action on neuronal responses to iontophoretically ejected gamma-amino butyric acid (GABA). In later studies, the action of 5-HT was examined on epileptiform discharges, evoked in the presence of the GABA antagonist, bicuculline, in the same group of cells. Droplet application of 5-HT into the recording chamber, or perfusion of 10 microM 5-HT regularly attenuated the length of epileptiform bursts but, at this concentration, had no discernible effect on the resting membrane potential or membrane input resistance. The effect of 5-HT on the release of glutamate from slices of entorhinal cortex has also been examined using a fluorometric enzyme assay. Concentrations of 5-HT as large as 30 microM had no effect on the release of endogenous glutamate in these experiments.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Electrophysiological evidence for excitatory 5-HT2 and depressant 5-HT1A receptors on neurones of the rat midbrain tectum.

It has been claimed that the aversive behaviour induced by electrical stimulation of the midbrain tectum (MT) has validity as an animal model of panic attack. A great deal of evidence obtained from behavioural studies suggests that 5-HT2 mechanisms phasically inhibit the substrates of aversion in the MT. In order to test this hypothesis we employed the technique of microiontophoresis of drugs onto neurons of the MT to assess the identity of the receptors mediating the effects of 5-hydroxytryptamine (5-HT). The results obtained show that the majority of 5-HT responsive cells in MT are cells excited by 5-HT (72%). These cells were silent or showed very low spontaneous firing activity, whereas cells depressed by 5-HT showed high spontaneous firing activity at baseline. The 5-HT1A receptor agonists, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), buspirone and gepirone caused consistent reduction in the firing rate of cells depressed by 5-HT while they did not change the firing activity of cells excited by 5-HT. The excitatory effects induced by 5-HT on MT neurones were clearly attenuated by concomitant application of ketanserin, a highly specific 5-HT2 antagonist. Excitatory responses to DL-homocysteic acid were not affected by ketanserin. Previous administration of zimelidine, a selective 5-HT uptake inhibitor, caused a significant enhancement of the excitatory effects of 5-HT while similar application of gepirone did not affect the size of the excitatory responses to 5-HT.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1991

Central antiaversive and antinociceptive effects of anterior pretectal nucleus stimulation: attenuation of autonomic and aversive effects of medial hypothalamic stimulation.

Previous studies have shown that stimulation of the rat anterior pretectal nucleus (APtN) strongly depresses a spinal reflex to noxious heat without causing significant aversion or depression of other motor responses. It is not known if APtN stimulation can similarly reduce the aversiveness of electrical stimulation of the brain, nor is it known if APtN stimulation is itself rewarding or aversive. This study used a simple switch-off paradigm to examine the rewarding properties of APtN stimulation at different sites throughout the nucleus and also used the tail-flick test to determine if the stimulation produced antinociception. The effects of APtN stimulation on the behavioural and autonomic responses to electrical stimulation of the medial hypothalamus (MH) and the nucleus raphe magnus (NRM) were also examined. The results show that electrical stimulation of dorsal APtN was rewarding and also caused antinociception which lasted for 50 min. However, sites which gave the strongest reward were not necessarily those which gave the greatest antinociception, as these effects were not correlated. Electrical stimulation of ventral APtN induced only aversive effects. The aversive and autonomic effects of MH stimulation were significantly reduced by conditioning stimulation of dorsal APtN. However, the very similar escape and autonomic effects of NRM stimulation were unaffected by APtN stimulation. These results suggest that electrical stimulation of the dorsal parts of the APtN has positive rewarding properties as well as the well-known antinociceptive effects. The antiaversive effects of dorsal APtN stimulation may be due in part to the inhibition of central substrates of aversion as well as inhibition of sensory neurones.

Animals↗
PubMed1991

The prevalence of cognitive impairment in a community survey of multiple sclerosis.

A one in two alternate sample (N = 200) from a population-based register of 411 people with multiple sclerosis (MS) was studied. Out of this sample, 147 people with MS and 34 people with rheumatoid arthritis were interviewed at home and completed a battery of neuropsychological tests. Cognitive impairment was found in 46 per cent of those with MS, with memory impairment in 34 per cent and failure on tests of frontal lobe function in 33 per cent. Physical disability was associated with cognitive impairment. Memory impairment was more common in those who had had MS for 10 years or more. A significant minority of people with mild physical disability and some who had had MS for less than a decade nevertheless had cognitive impairment. Relationships between cognitive impairment, other disease variables and psychosocial factors were examined. Counselling and rehabilitation programmes for people with MS and their families should take account of cognitive deficits that may be present.

Adult↗
PubMed1991

The prevalence of multiple sclerosis in the Southampton and South West Hampshire Health Authority.

A first survey of the Southampton and South West Hampshire Health Authority showed an overall prevalence of multiple sclerosis of 99/100,000 in a population of 417,000 on 1 January 1987. This finding is similar to other recent first surveys in the South of the United Kingdom and only repeat surveys will show if case only repeat surveys will show if case ascertainment has been more complete in these than earlier first studies in Scotland.

Adolescent↗
PubMed1991

Monoclonal antibodies recognize localized antigens in the eye and central nervous system of the marine snail Bulla gouldiana.

The eyes of the marine snail Bulla gouldiana act as circadian pacemakers. The eyes exhibit a circadian variation in spontaneous optic nerve compound action potential frequency in constant darkness, and are involved in controlling circadian rhythms in behavioral activity expressed by the animal. To initiate an investigation of the molecular aspects of circadian rhythmicity in the Bulla eye and to identify specific molecular markers in the nervous system, we raised monoclonal antibodies (MAb) to the eye and screened them for specific patterns of staining in the eye and brain. Several MAb recognize antigens specific to groups of neurons in the brain, whereas others stain antigens found only in the eye. In addition, some antigens are shared by the eye and the brain. The antigens described here include molecules that mark the lens, retina, neural pathways between the eye and the brain, specific groups of neurons within the central ganglia, and an antigen that is shared by basal retinal neurons (putative ocular circadian pacemaker cells) and glia. These molecular markers may have utility in identifying functionally related groups of neurons, elucidating molecular specializations of the retina, and highlighting pathways used in transmission of information between the retina and the brain.

Animals↗
PubMed1990

The actions of the novel anti-aggressive drug eltoprazine on central neurones in the anaesthetised rat.

5-Hydroxytryptamine (5-HT) and the novel anti-aggressive drug eltoprazine (1-(2,3-dihydro-1,4-benzodioxin-5-yl) piperazine hydrochloride) were applied by microiontophoresis to spinal motorneurones and also to neurones in the brainstem which gave two distinctly different responses to 5-HT. In vitro microiontophoretic release studies showed that the electrophoretic mobility of eltoprazine and 5-HT were similar and that similar amounts of each drug would be applied by similar iontophoretic currents. Cells in the brainstem have been shown previously to be excited by 5-HT, acting at a 5-HT2 receptor. Eltoprazine only occasionally and weakly mimicked the excitatory effect of 5-HT on these cells. Although a potent antagonism of the 5-HT excitation by eltoprazine was observed, this was a non-selective effect, as responses to glutamate and D,L-homocysteic acid were also reduced. Cells in the lateral brainstem are depressed by 5-HT, acting on a receptor which has previously been shown to be of the 5-HT1-like group. At this receptor, 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)-tetralin) and 5-carboxamidotryptamine, are potent agonists. Eltoprazine was a more potent depressant agonist than 5-HT on these brainstem neurones. The antagonist metergoline did not antagonise responses to either 5-HT or eltoprazine. It is suggested however that both drugs act at the same receptor to depress these cells because desensitizing the receptor by repeated, frequent applications of 5-HT abolished responses to 5-HT and eltoprazine, without altering responses to GABA.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1989

Kinase inhibition lengthens the period of the circadian pacemaker in the eye of Bulla gouldiana.

The inhibition of protein kinase activity by the isoquinoline sulfonamide, H-8, lengthens the period of the Bulla ocular circadian rhythm in a dose-dependent manner. In addition, the phosphorylation of 5 proteins is markedly affected by H-8. The observed correlation between H-8's period lengthening effects, and its effects on the phosphorylation of specific proteins, suggests that: (1) these proteins are candidate components regulating the period of the circadian rhythm; and (2) the daily changes in membrane potential underlying the circadian rhythm are mediated by similar mechanisms that serve to change neural function in other systems; modulation of protein kinases.

Animals↗
PubMed1989

Afferent projections to the rostral anterior pretectal nucleus of the rat: a possible role in the processing of noxious stimuli.

The afferent inputs to the rostral pole of the anterior pretectal nucleus have been examined by utilizing the retrograde axonal transport of a fluorescent dye, Fast Blue. After unilateral injection of the dye into the rostral anterior prectectal nucleus, large numbers of labelled neuronal somata were found in the somatosensory cortex, the ventrolateral geniculate nucleus, the zona incerta, the superior colliculus, the deep mesencephalic nuclei, the pedunculopontine tegmental nucleus and the medial vestibular nucleus. In addition, the contralateral parabigeminal nucleus provided a major input to the rostral part of the anterior pretectal nucleus. Smaller and sparser collections of stained cell bodies could be found in the ventromedial hypothalamus, the posterior pretectal nucleus, the nucleus of the posterior commissure, the peripeduncular nucleus, the periaqueductal central gray, the contralateral anterior pretectal nucleus, and the locus coeruleus. Many of the inputs originated in areas associated with nociceptive pathways. The regional distribution of neurons projecting to the rostral pole of the anterior pretectal nucleus differs substantially from that of the cells innervating the anterior pretectal nucleus proper, i.e. its more caudal parts. It is concluded from this that the rostral pole constitutes a separate nucleus, anatomically distinct from the rest of the anterior pretectal nucleus and other cell groups in the pretectal complex. The demonstration that many of the afferents to the rostral anterior pretectal nucleus arise in regions involved in nociception supports recent electrophysiological and behavioural evidence that this brain area plays a role in the processing of noxious stimuli, rather than as a component in the pretectal control of visual system reflexes.

Afferent Pathways↗
PubMed1989

Structural and functional analysis of raphe neurone implants into denervated rat spinal cord.

The ability of grafts of embryonic raphe cells to the adult rat spinal cord to reverse the morphological, neurochemical and functional deficits caused by ablation of the serotoninergic afferents has been studied. After grafting, extensive reinnervation was observed by 5HT-immunoreactive fibres, many of which appeared to make contacts with host motoneurones. The neurotransmitter complement was apparently normal. There was also a reinstatement of 5HT levels in the denervated cord after transplantation, amounting to some 40% of normal at the level of the graft. Similarly, Na+-dependent uptake of [3H]-5HT into P3 fractions was over 40% of that recorded in unlesioned animals. Antidromic stimulation of the ventral roots of the spinal cord was used to assess the degree of motoneurone excitability. The field potential in the ventral horn of grafted animals was increased by electrical stimulation of discrete regions along the cord, probably corresponding to the graft loci. It is concluded that serotoninergic neurones transplanted to the denervated spinal cord survive and develop normally, reinnervating the host tissue extensively. Furthermore, the graft/host connections appear to be functionally viable.

Action Potentials↗