Biomedical subjects

P R Laming

Publications and source records attributed to P R Laming.

At least 19 recordsLinked to original sources

PubMed2000

Neuronal-glial interactions and behaviour.

Both neurons and glia interact dynamically to enable information processing and behaviour. They have had increasingly intimate, numerous and differentiated associations during brain evolution. Radial glia form a scaffold for neuronal developmental migration and astrocytes enable later synapse elimination. Functionally syncytial glial cells are depolarised by elevated potassium to generate slow potential shifts that are quantitatively related to arousal, levels of motivation and accompany learning. Potassium stimulates astrocytic glycogenolysis and neuronal oxidative metabolism, the former of which is necessary for passive avoidance learning in chicks. Neurons oxidatively metabolise lactate/pyruvate derived from astrocytic glycolysis as their major energy source, stimulated by elevated glutamate. In astrocytes, noradrenaline activates both glycogenolysis and oxidative metabolism. Neuronal glutamate depends crucially on the supply of astrocytically derived glutamine. Released glutamate depolarises astrocytes and their handling of potassium and induces waves of elevated intracellular calcium. Serotonin causes astrocytic hyperpolarisation. Astrocytes alter their physical relationships with neurons to regulate neuronal communication in the hypothalamus during lactation, parturition and dehydration and in response to steroid hormones. There is also structural plasticity of astrocytes during learning in cortex and cerebellum.

Animals↗

PubMed2000

Potassium signalling in the brain: its role in behaviour.

This paper examines evidence that glial cells respond to changes in extracellular potassium ([K+]e) in ways that contribute to modulation of neuronal activity and thereby behaviour. Glial cells spatially (and probably directionally) redistribute potassium from regions of increasing concentration to those with a lesser concentration. This redistribution is largely responsible for slow potential shifts associated with behavioural responses of animals. These slow shifts are related in amplitude to the level of 'arousal' of an animal, and its motivational state. In addition, glia, especially astrocytes, respond to changes in [K+]e, the presence of transmitters like nor-adrenaline and glutamate and at least some hormones with changes in their metabolism and/or the morphological characteristics of the cell. The ionic, metabolic and morphological responses of glia to changes in extracellular potassium after neuronal activity have been associated with at least some forms of learning, including habituation, one trial passive avoidance learning and changes associated with enriched environments. The implication of these effects of potassium signalling in the brain is that there is considerable involvement of glia in a number of processes crucial to neuronal activity. Glia may also form another route for information distribution in the brain that is at least bi-directional, though less specific than its neuronal counterparts. It is evident that the Neuroscience of the future will have to incorporate much more study of neuron-glial interactions than hitherto.

Animals↗

PubMed1998

Epicortical slow potential shifts and sensory-evoked potentials are related to seizure propensity in gerbils.

Gerbils were assessed for behavioral tendency by scoring seizure severity and the amount of ambulatory and rearing activities in a novel 'open-field' arena. Seizure-prone animals exhibited seizures on early open-field trials (1-2) and later performed more ambulatory activity than non-seizure-prone animals. Two weeks later, two groups of both seizure prone and non-seizure prone animals were chronically implanted with six silver/silver chloride ball electrodes for recordings during behaviour. Electrodes were on the surfaces of the frontal, parietal and occipital cortices bilaterally. In one group these were used to record slow potential shifts; in the other, visual- and acoustic-evoked responses. Larger negative and positive slow shifts occurred in seizure-prone animals. Most evident were the larger positive right frontal shifts and negative left occipital shifts. Seizure tendency was related to the amplitude of these waveforms. Visual-evoked potential amplitudes were generally larger and latencies shorter in seizure-prone animals, especially in the right occipital and left parietal cortices. Seizure susceptibility was associated with increased visual-evoked potential amplitude in the right frontal and left occipital cortices, and with reduced latency of both auditory- and visual-evoked responses in the left occipital cortex. The discussion highlights a role for glia in slow shift generation and the association of large shifts with enhanced sensory-evoked responses, especially in seizure-prone animals.

Animals↗

PubMed1998

Large slow potential shifts occur during halothane anaesthesia in gerbils.

Continuous recordings were made of slow potential shift activity occurring at six locations on the surface of the cerebral cortex of seizure-prone and non seizure-prone gerbils. Measurements were made for 80-s epochs of recordings of frequency, maximum and minimum slow shift amplitude and baseline potential of the brain during periods of normal inactivity and subsequently during halothane anaesthesia. Induction of anaesthesia initially provoked large (millivolt) slow (3-4 s) oscillations in all animals, larger in amplitude than any recorded prior to anaesthesia. With increasing depth of anaesthesia, all animals also showed a reduction in the amplitude of this spontaneous slow potential shift activity. The effect was most pronounced in seizure-prone animals, and subsequent to anaesthetic-induced behavioural immobility, these animals also showed a regional resistance to the depression of spontaneous slow potential shift oscillations. Slow potential shift activity during anaesthesia represents ionic fluxes which may normally be involved in modulation of neuronal responsiveness. It was suggested that glia may be targets for anaesthetics and that seizure susceptibility may confer some degree of resistance to the depressant effects of such substances.

Anesthesia↗

PubMed1998

Effects of food, glucose, and water ingestion on feeding activity in the toad (Bufo bufo).

Feeding in toads was tested by orient, approach, fixate, and snap responses to an artificial prey stimulus, before and at various times after feeding with natural prey (mealworms), or infusion of the gut with a prey-equivalent amount of glucose or volume of water. Feeding 5 prey objects or ad libitum feeding caused a decline in a prey catching when tested 2 hr later. Ingestion of 5 pulped mealworms or the equivalent glucose content and volume similarly decreased prey-catching, though an equal volume of water had no effect. Comparisons of the effect of time after glucose ingestion on prey-catching activity demonstrated that the major decline in activity occurred within 15 min, with no appreciable change after 2 hr. An equal volume of water had little effect on prey-catching activity over 15 min, but subsequent glucose ingestion reduced these behaviors. Thus, the decline in prey catching that occurs after feeding in toads can be rapidly replicated by ingestion of glucose, allowing future examination of the neural basis of satiety in these animals.

Analysis of Variance↗

PubMed1995

Sustained potential shifts in the toad tectum reflect prey-catching and avoidance behavior.

Sustained potential shifts (SPS) were recorded for 10 s from the surface of the optic tectum of toads presented with live prey and moving artificial prey stimuli. On the anterior tectal surface, a negative SPS was followed by a positive wave; the converse was true for the posterior tectum. Some animals were immobilized, and they exhibited a monophasic negative SPS in the anterior tectum and a positive wave in more posterior regions. The number of orienting responses made by toads to moving "wormlike" stimuli was reflected in the amplitude of the SPS, as was avoidance to stimuli in an "antiworm" configuration. Behavioral activity was most closely related to the negativity of the SPS recording. The SPS of toads responding to live prey showed no direct time relationship between the SPS and behavior, suggesting that the SPS reflects sensory or decision-making activity rather than the consequent behavior.

Animals↗

PubMed1993

Brain amino acid levels are related to seizure propensity in the gerbil (Meriones unguiculatus).

1. Gerbils were scored for seizure severity and duration and ambulatory and rearing behaviours on presentation with an "open field". 2. Eight seizure-prone (SP) and eight non-seizure-prone (NSP) gerbils were killed and their brains treated to inactivate enzymes before division into corticate and decorticate regions for amino acid analysis. 3. SP animals showed more ambulatory activity on later presentations (trials 3-5) with the open field compared to NSP animals. 4. Statistics showed seizure propensity related to high levels of glutamine and arginine and to low levels of glutamate, aspartate, citrulline, cysteine and glycine. 5. These results suggest aspects of glucose and/or amino acid metabolism may be responsible for behavioural differences in SP compared to NSP gerbils.

Amino Acids↗

PubMed1992

Stimulus-evoked slow potential shifts and changes in [K+]0 of the frog optic tectum.

In 17 frogs (Rana esculenta var ridibunda) immobilised with succinyl choline the optic tectal surface was stimulated by trains of electrical pulses or by a flash to the contralateral eye. Sustained potential shifts (SPSs) and changes in extracellular potassium concentration (delta[K+]0) were simultaneously recorded. In response to electrical stimulation SPSs of maximal amplitudes (1.19 +/- 0.1 mV) were recorded between 50 and 200 microns in depth and maximal delta[K+]0 (0.69 +/- 0.08 mM) between 100 and 350 microns. The changes of SPS and delta[K+]0 showed a close similarity in experiments with changes in voltage, pulse duration and frequency of stimuli within a train. The induced SPS had a duration of 28 +/- 1.54 s, the delta[K+]0 of 32 +/- 1.23 s. The flash stimulus induced an SPS and delta[K+]0 of maximal amplitudes between 50 and 200 microns in depth with values of 0.57 +/- 0.1 mV and 0.29 +/- 0.03 mM respectively. An additional wave with a latency of ca 1 s and a duration of ca 3 s arose on the background of the SPS to a flash stimulus, associated with an additional increase in [K+]0. It is considered that the accumulation of K+ in extracellular space, with neuronal activity, results in depolarization of radial processes of ependymal glia. This is reflected in the neuropil of the upper layers of the optic tectum as an SPS.

Animals↗

PubMed1992

Sustained potential shift responses and their relationship to the ECG response during arousal in the goldfish (Carassius auratus).

1. Goldfish, when presented with a 10 sec light-on stimulus against a background of 2 hr of sensory restriction, exhibited sustained potential shift (SPS) activity, of differing polarity, at each of four surface recording sites, on the medulla, cerebellum, optic tectum and telencephalon. 2. Principle components analysis (PCA) indicated that SPS responses from each region comprised superimposed early and late waveforms. At the cerebellar, tectal and telencephalic surfaces, neuronal activity appeared to contribute strongly to the early (less than 2 sec) SPS waveform. 3. While, in response to repeated stimulus presentations, habituation was apparent in the early SPS waveforms recorded from the medulla, cerebellum and telencephalon, an increase in negativity occurred in late SPS waveforms throughout the brain. 4. The tectal SPS response was directly proportional to the telencephalic SPS response both in terms of average SPS amplitudes following the first presentation of the light-on stimulus and in terms of their increasing negativity in response to stimulus repetition. 5. The increasing negativity of the telencephalic SPS was also associated with the habituation of the ECG response over repeated trials. 6. Results are discussed with regard to a possible neuromodulatory role for glia.

Analysis of Variance↗

PubMed1992

Dendritic and sustained shifts in potential to electrical stimulation of the anuran tectal surface.

1. Recordings of dendritic potentials and sustained potential shifts (SPS) were made from the brain of immobilised frogs during surface tectal electrical stimulation. 2. Single pulses evoked dendritic responses; trains caused decay of dendritic responses on the background of the evoked SPS. 3. The tectal surface SPS declined with distance from the stimulating electrode. 4. The negative surface SPS declined with tectal depth to ca 300 microns, then reversed polarity and increased in amplitude with depth up to 700 microns.

Animals↗

PubMed1991

Changes in early acoustic-evoked potentials by mildly arousing priming stimuli in carp (Cyprinus carpio).

1. Averaged acoustic-evoked potential (AEPs) in the medulla and midbrain were recorded, as were changes in heart rate, indicating arousal, to a previous non-acoustic priming stimulus. 2. Useful AEP measures were amplitude of the early biphasic wave (less than 10 msec) in medulla and amplitude and duration of this wave in midbrain. 3. There was a negative regression of heart rate and medullary AEP amplitude especially evident for a 2 sec light stimulus. Decreased AEP amplitude in both regions was induced by water movement and an increase in midbrain AEP duration by the tactile stimulus. 4. Arousal effects even on these early AEP measures are specific to the form of arousing stimulus.

Animals↗

PubMed1991

Changes in EEG power, acoustic evoked potentials and heart rate after mildly arousing non-acoustic priming stimuli in carp (Cyprinus carpio).

1. Changes in EEG power spectrum of carp to a priming non-acoustic stimulus followed by acoustic clicks were compared to those due to acoustic clicks delivered alone. Recordings were made from the telencephalon, midbrain and medulla. Acoustic evoked potentials (AEPs) to the clicks were also recorded. 2. EEG power changes to non-acoustic stimuli occurred over the whole 1-40 Hz frequency range and were regionally specific and consistent. 3. The changes in the EEG midfrequency 12-24 Hz power spectrum to non-acoustic stimuli were significantly correlated with changes in the AEP to subsequent clicks. An elevated medullary AEP amplitude and reduced duration were correlated with increased medullary EEG power and increased midbrain AEP duration. 4. Telencephalic EEG power changes were inversely related to changes in medullary and midbrain AEP amplitude.

Acoustic Stimulation↗

PubMed1991

Sustained potential shifts and changes in acoustic evoked potentials after presentation of a non-acoustic priming stimulus to carp (Cyprinus carpio).

1. Recordings were made from the region of the midbrain tectum and torus semicircularis of sustained potential shifts (SPS) to a non-acoustic priming stimulus and the change in subsequent acoustic evoked potentials (AEPs) to a train of six clicks after a long rest. 2. In the absence of priming stimuli (a jet of saline or water to the flank) the AEP to the first click in a train had the highest amplitude; with these stimuli it became the most attenuated. 3. The SPS to both non-acoustic stimuli was initially (ca 4 sec) negative, then became positive for a similar time period. 4. After saline jet the tectal and the torus AEP amplitude was significantly correlated with the torus SPS; after water jet, the tectal and the torus AEP durations were correlated with the SPS. 5. Application of alumina gel to the posterior telencephalic border caused elevation of the torus AEP amplitude after some 5 hr.

Acoustic Stimulation↗

PubMed1990

Habituation in goldfish (Carassius auratus) is impaired by increased interstimulus interval, interval variability, and telencephalic ablation.

Goldfish (Carassius auratus) were fitted with electrodes and buccal catheters for monitoring electrocardiograms and ventilations, respectively. A 2-s "light-on" stimulus was repeatedly presented to groups of fish at fixed interstimulus intervals (ISIs) of 1 or 2 min or at variable ISIs with a mean duration of 1 or 2 min. Normal fish, fish with telencephalic ablation, and fish with sham operations were compared for responsiveness and habituation to repeatedly presented stimuli. The longer the ISI, the greater the number of stimuli that were required for habituation. Increased ISI variability also decreased the rate of habituation. Furthermore, fish with telencephalic ablation had significantly slower habituation rates with both fixed and variable ISI schedules.

Animals↗

PubMed1989

Do glia contribute to behaviour? A neuromodulatory review.

1. The links between behavioural state, gross electrophysiology and the activity of neurons and astrocytes are reviewed to stimulate interest in the contributions that glia make to behaviour. 2. Behavioural arousal in which neuronal responsivity ("sensitivity") is elevated is also associated with a sustained (0.5-10 sec) potential shift (SPS). 3. There is powerful and accumulating evidence that the SPS is primarily of glial origin. 4. In epilepsy neurons are hyperactive and there is a massive SPS during seizures. In seizure free periods, epileptic animals frequently have elevated arousal responses and increased neuronal sensitivity, indicating that seizures may be due to elevation of the activity of a normally adaptive sensitizing mechanism. 5. The common finding of an astrocytic pathology in epilepsy and the links between arousal, neuronal sensitization, SPSs and seizures implicates a modulatory role for astrocytes in both health and disease. 6. Glia, especially astrocytes, may modulate neuronal responsiveness by regulation of the microenvironment. 7. At the current state of knowledge, regulation of extracellular ionic K+, Ca2+ and neurotransmitter glutamate and GABA seem to be the most important candidates for modulating neuronal sensitivity in arousal and abnormally for seizure genesis. 8. Both in phylogeny and in ontogeny, glia and neurons have intimate associations. 9. The functional astrocytic syncitium is in a prime position to control the ecology of neuronal populations and thereby their activity. 10. The physiology and biochemistry of glia-neuronal interactions offers exciting new prospects for developments in behavioural neuroscience.

Animals↗

PubMed1989

Seizures in the Mongolian gerbil are related to a deficiency in cerebral glutamine synthetase.

1. Seizure prone (SP)-gerbils (Meriones unguiculatus) tested repeatedly in an open field exhibited habituation of seizures after one or two trials and subsequently showed more ambulatory activity than non-seizure prone (NSP) individuals. 2. A subset of 5 SP and 5 NSP animals were killed and portions of each cerebral hemisphere, the cerebellum and the brainstem medulla were analysed for glutamine synthetase (GS). 3. GFAP immunohistochemistry was used on forebrain sections to assay astrocyte density. 4. It was found by MANOVA, PCA and regression analyses that seizures and ambulatory activity were related to a deficiency in cerebral GS. 5. Rearing behaviour was related to medullary brainstem and cerebellar GS concentrations. 6. The decreased GS of the seizure-prone gerbils was not apparently associated with a deficiency of astrocytes, perhaps the reverse. 7. The results are discussed in relation to glial-neuronal interactions modulating arousal and the propensity for seizures.

Animals↗

PubMed1989

Epileptic tendencies in relation to behavioral responses to a novel environment in the Mongolian gerbil.

The severity of epileptic-like seizures in gerbils (Meriones unguiculatus), placed in an open field, is directly related to their ambulatory activity on subsequent trials. An inverse relationship, however, occurs between seizure severity and oriented, bipedal rearing behavior on subsequent trials. Principal components and multiple linear regression analyses support the hypothesis that ambulation and rearing have different underlying neuronal mechanisms. If these two activities are considered as measures of arousal and attention, respectively, then epileptic-like seizures may be caused by hyperactivity of mechanisms which induce arousal.

Animals↗

PubMed1988

Cardiac, ventilatory and behavioural arousal responses evoked by electrical brain stimulation in the goldfish (Carassius auratus).

Goldfish (Carassius auratus) were fitted with intracranial stainless steel microelectrodes for electrical evocation of behavioural arousal and its cardiac and ventilatory correlates. Behaviour was monitored on a videosystem and ECG electrodes and a buccal catheter were implanted to monitor physiological responses. Thresholds for responses were described in relation to the current spread likely to excite CNS tissue. Two types of responses were obtained. These were (A) cardiac and ventilatory responses alone, apparently due to stimulation of primary sensory pathways and (B) these responses and behavioural arousal responses which were elicited at higher thresholds. These latter, more complete expressions of arousal resulted from stimulation of the Dm/Dc region of the telencephalon, the dorsal diencephalon and the midbrain tegmentum. Response thresholds were higher and physiological response magnitudes lower in the midbrain tegmentum compared to the forebrain regions.

Animals↗