Biomedical subjects

G J Lees

Publications and source records attributed to G J Lees.

At least 55 records · Page 3Linked to original sources

PubMed1985

State-changes in the brain viewed as linear steady-states and non-linear transitions between steady-states.

Preceding papers concern a linear theory of electrocortical waves and their regulation by brain-stem neurones, in conditions of steady-state. The present paper reconsiders the theory, and generalizes beyond the effects of the fibre systems so far studied. Relaxation and unification of the assumptions upon which the initial model was based is undertaken. It is shown that the generalised model may render state changes within the brain accessible to systematic description, using the EEG as dependent variable. It is proposed that a multitude of stable states are possible within the brain, each characterised by a set of damping parameters for separate linear resonant modes. Within each stable state, the set of sums of resonant modes characterises a sub-space of the total state-space. Transition between stable regions can occur with either perturbation by external signals, or by internal controls. Tentative consideration is given to the role of plastic changes leading to adaptive learning as an attribute of a system of this type.

Cerebral Cortex↗

PubMed1985

Quantitation of a mass action of dopaminergic neurones regulating temporal damping of linear electrocortical waves.

We have previously proposed that electrocortical waves are linear waves, subject to regulation by mesotelencephalic dopaminergic neurones. As a further means to test this theory, selective unilateral lesions of varying extent were made in the nucleii of origin of the dopaminergic mesotelencephalic tract. Changes in the electrocortical power spectrum were assessed by a repeated measure, between hemispheres comparison of ratio changes in power. With increasing unilateral dopamine cell damage, the animals showed increasing contralateral sensorimotor neglect. Curve fitting the ratio changes in power attributable to lesion, showed that estimates of the power of driving signals and the temporal damping moved in reverse directions with increasing extent of lesion, as expected from the theory. A further test was undertaken, to determine whether equal estimates for a transformation of surface signals were obtained from each side. Equality would not be expected if the equation for relative power were invalid. Left and right equality was found for three grades of unilateral lesion.

Animals↗

PubMed1985

Relationship between sensorimotor neglect and the specificity, degree and locus of mesotelencephalic dopaminergic cell loss following 6-hydroxydopamine.

The involvement of cell groups within the dopaminergic mesotelencephalic system in the development of the sensorimotor neglect syndrome was re-evaluated in two ways. Firstly, dopaminergic specificity of the neglect was further established by studying the relationship between nomifensine protection of dopamine cells against 6-hydroxydopamine damage and the degree of neglect which resulted. The sensorimotor neglect syndrome which developed following injection of 6-hydroxydopamine was diminished by concomitant treatment with nomifensine in parallel with the degree of protection afforded the dopaminergic cells. Non-specific damage produced by 6-hydroxydopamine was unaltered by nomifensine. Secondly, the role in sensorimotor neglect of both total cell damage, and damage to regional sub-classes of dopaminergic cells was considered. It was found that the extent of the resulting neglect was correlated with the overall damage to the substantia nigra and ventral tegmental area, rather than to any individual region within this dopaminergic system. There was a threshold, involving destruction of approximately one third of the system, below which no neglect syndrome developed. Certain regions, including the ventral tegmental area (VTA), showed a higher partial correlation with the extent of neglect than other regions. While specific lesioning of the A8 or A10 dopaminergic neurons is probably insufficient to produce a neglect syndrome, damage to these areas potentiates the severity of the neglect produced by nigrostriatal lesions. It appears that the involvement of the individual subclasses of the mesotelencephalic dopaminergic neurons in the neglect syndrome is more widespread than previously thought.

Animals↗

PubMed1985

Contributions of noradrenergic neurones of the locus coeruleus to the temporal damping of linear electrocortical waves.

The preceeding paper (Wright et al. 1985a) gives evidence that mesotelencephalic dopaminergic neurones regulate gross electrocortical waves with linear properties, by influencing the strength of their driving signals and temporal damping. The present study further generalises the findings to ascending noradrenergic neurones, which have different fields of termination to dopaminergic fibres. It is shown that: Estimates of the major groups of natural frequencies for the telencephalic system obtained from curve-fitting the ratio changes in the power spectrum attributable to unilateral noradrenergic neurone lesion, are again centered about the frequencies of the major cerebral rhythms. Estimates of electrode transfer characteristics, using parameters obtained from curve fitting ratio changes in power, in conjunction with the raw left and right power spectra, are again found to be equal left and right, as required by the theoretical derivation. Changes in relative amplitude of electrocortical waves and their relative phase are significantly in accord with the relationship expected from theory.

Animals↗

PubMed1984

Effect of nomifensine on the toxicity of 6-hydroxydopamine for mesotelencephalic dopamine neurons.

The ability of nomifensine to protect the dopaminergic cells of the substantia nigra and ventral tegmental areas against 6-hydroxydopamine-induced destruction was evaluated. Nomifensine at high doses (20 mg/kg, i.p.) protected the cells from the effects of low amounts of 6-hydroxydopamine (2 micrograms) injected intracerebrally. This protective effect was markedly decreased with an increased amount of 6-hydroxydopamine (8 micrograms), or by lower doses of nomifensine (6.7 mg/kg). These doses of nomifensine are higher than those required to protect dopaminergic nerve terminals.

Animals↗

PubMed1984

Differences in properties between aromatic amino acid: aromatic keto acid aminotransferases and aromatic amino acid: alpha-ketoglutarate aminotransferases.

Homogenates of rat liver transaminate phenylpyruvate (PP), as well as alpha-ketoglutarate (alpha-KG), in the presence of L-tyrosine, 3,4-dihydroxyphenylalanine (L-DOPA) or L-tryptophan. Aminotransferase activity with phenylpyruvate and DOPA, but not with tyrosine, was inhibited by excess phenylpyruvate. Tyrosine and DOPA aminotransferase activities with phenylpyruvate were more heat stable than the corresponding activities with alpha-ketoglutarate. Aminotransferase activities with phenylpyruvate were not significantly induced following intraperitoneal injections of cortisol, glucagon or serotonin, compared with a 3 to 7-fold increase in the aminotransferase activities with alpha-ketoglutarate. Tyrosine:phenylpyruvate aminotransferase activity rose 40% at night, compared with a 300% increase in tyrosine:alpha-ketoglutarate aminotransferase activity. The results suggest that aminotransferases catalysing transfers between aromatic keto acids and aromatic amino acids are separate enzymes from those utilizing alpha-ketoglutarate as the acceptor keto acid.

Animals↗

PubMed1984

Retrograde transport of dopamine beta-hydroxylase antibodies in sympathetic neurons: effects of drugs modifying noradrenergic transmission.

Antibodies to dopamine beta-hydroxylase (anti-D beta H) were taken up by noradrenergic nerve terminals in the iris following attachment to D beta H, and were transported back to, and accumulated in, the superior cervical ganglion (SCG). Concurrent, or prior destruction of noradrenergic terminals with 6-hydroxydopamine, injected intraocularly, blocked the retrograde transport of anti-D beta H. However, recovery was rapid, reaching 50% of control values within 1 day. Such transport was characterized by a shorter time period before accumulation could be detected in the SCG and by a slower rate of accumulation. These results suggest that noradrenergic neurons recover their ability to turn over synaptic vesicles by exocytosis and transport these back to the ganglion early during the period of axonal regeneration when the axonal length is shorter than normal. The uptake and transport of anti-D beta H was regulated by alpha-adrenergic agents administered locally in the vicinity of noradrenergic nerve terminals. Thus intraocular injection of phentolamine resulted in an increased accumulation of anti-D beta H in the SCG, while amphetamine and the postsynaptic alpha-receptor antagonist, phenylephrine, decreased accumulation. Clonidine and desipramine, which have a predominant presynaptic action, failed to influence the transport of anti-D beta H. These results suggest that in vivo the uptake of anti-D beta H can be increased more by local postsynaptic reflex actions than by a mechanism depending on the inhibition of presynaptic alpha-receptors.

Amphetamine↗

PubMed1984

Amplitude and phase relations of electrocortical waves regulated by transhypothalamic dopaminergic neurones: a test for a linear theory.

We have previously proposed that electrocortical activity (EEG) arises as a manifestation of linear waves generated by resonance among telencephalic neurones, and that this activity is controlled in part by ascending neurones from the brain-stem, which regulate the damping of each resonance. The present experiments focus on a specific class of ascending neurones, the mesotelencephalic dopaminergic cells, because these cells are thought to mediate important psychological effects, and are conveniently subject to selective lesion. A critical test of the theory is undertaken, by performing selective unilateral lesion, assessing the changes in the power spectrum of the EEG attributable to lesion, and determining whether the changes in phase of the EEG correspond to that predicted from the changes in power. Results support the theory, although the model order applicable in these experiments in inadequate. The consequences of these findings for automata theory, linear network theory and their application to mammalian brains are briefly discussed.

Animals↗

PubMed1984

Effect of oxygen on the induction of tryptophan hydroxylase by adrenergic agents in organ cultures of rat pineal glands.

Rat pineal glands, cultured under 95% air and 5% CO2, lost 50% of their tryptophan hydroxylase activity within 5 h. This loss was accelerated by the addition of cycloheximide or puromycin to the medium. Activity was, however, largely maintained in 95% O2 and 5% CO2. Under these conditions, L-noradrenaline (100 microM), L-isoproterenol (10 microM), and dibutyryl cyclic AMP (1 mM) induced enzyme activity. They failed to do so when 95% air and 5% CO2 was used. Noradrenaline induced serotonin N-acetyltransferase activity with either atmosphere.

Animals↗

PubMed1981

Phentolamine increases neuronal binding and retrograde transport of dopamine beta-hydroxylase antibodies.

When 125I-labelled antibodies against dopamine beta-hydroxylase (DBH) were injected into the anterior eye chamber of guinea-pigs they bound to sympathetic nerve terminals, were internalized into the axons and retrogradely transported to the ipsilateral superior cervical ganglion (SCG). This process was demonstrated to depend on specific binding sites since neutralized antibodies were not taken up and transported. The alpha-receptor antagonist phentolamine caused a 2.5-fold increase in binding in the iris and a 2.1-fold increase in accumulation of [125I]anti-DBH in the SCG. The results demonstrate that retrograde axonal transport of synaptic vesicle components is coupled to their turnover in nerve terminals.

Afferent Pathways↗

PubMed1979