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P Redgrave

Publications and source records attributed to P Redgrave.

At least 73 records · Page 4Linked to original sources

Responses resembling defensive behaviour produced by microinjection of glutamate into superior colliculus of rats.

Electrical stimulation of the superior colliculus in rats elicits not only orienting movements, as it does in other mammals, but also behaviours resembling such natural defensive responses as prolonged freezing, cringing, shying, and fast running and jumping. To investigate the location of the cells mediating these behaviours, the superior colliculus was systematically mapped with microinjections of sodium L-glutamate (50 mM, 200 nl), and the resultant behavioural changes as assessed in an open field were analysed for defence-like responses. The main regions that gave defensive behaviour were (i) rostromedial superior colliculus (all layers), and (ii) both medial and lateral parts of the caudal deep layers. Cells in these areas project into the ipsilateral descending pathway. However, the cells of origin of this pathway are also found in collicular regions, such as rostral intermediate gray and parts of far caudal colliculus, that did not give defensive movements in response to glutamate stimulation. It is unclear whether this is because only parts of the ipsilateral pathway mediate defensive behaviours, or because glutamate is a relatively inefficient stimulating agent for these systems. An unexpected feature of the results was that at a number of collicular sites the nature of the defensive response changed with successive (up to three) injections of glutamate, often appearing to become more intense. Whether the mechanism underlying this potentiation is related to the conditioning of natural defensive behaviour is unknown.

Animals↗

Cardiovascular and respiratory changes elicited by stimulation of rat superior colliculus.

Stimulation of the rat superior colliculus can produce either orienting or defensive movements, which if elicited by natural stimuli would be accompanied by cardiovascular changes. To assess whether cardiovascular changes might also be mediated by the superior colliculus, blood pressure and heart rate were measured in Saffan-anaesthetised rats while the dorsal midbrain was systematically explored with electrical and chemical stimulation. Electrical stimulation (10 sec trains of 0.3 msec 100 Hz cathodal pulses, 50 microA) within the superficial and intermediate layers of the rostral superior colliculus transiently lowered blood pressure without affecting heart rate. In contrast sites within the deep layers, and in adjacent periaqueductal grey and midbrain tegmentum, gave pressor responses accompanied by a variety of heart-rate changes, that usually included a period of bradycardia. A roughly similar distribution was obtained with the cell-stimulant bicuculline (200 or 500 nl, 490 microM), though sodium L-glutamate (200 nl, 0.05 or 1.0 M) was ineffective. These results suggest that (a) cardiovascular responses can be produced by stimulation of the rat superior colliculus; (b) their nature depends on the location of the stimulation; and (c) they may be mediated in part by cells differentially sensitive to glutamate and to bicuculline. In addition, in some animals respiratory responses were measured stethographically. Short-latency increases in thoracic girth, often accompanied by increases in respiratory rate and depth, were elicited by electrical stimulation from 61% of the collicular sites examined, and by microinjection of glutamate from 56% of collicular sites. These data suggest that (a) cells within the superior colliculus are capable of influencing respiration; (b) given the widespread distribution of responsive sites within the superior colliculus, the respiratory changes may be preparatory for both approach and defensive movements; (c) the collicular cells that affect respiration may be different from those that influence blood pressure, because the latter are relatively insensitive to microinjection of glutamate.

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Further evidence for segregated output channels from superior colliculus in rat: ipsilateral tecto-pontine and tecto-cuneiform projections have different cells of origin.

Two of the targets of the ipsilateral descending pathway from the superior colliculus are the cuneiform area (immediately ventral to the inferior colliculus), and the dorsolateral basilar pons. The cells of origin of the projections to these targets in rat were studied with a retrograde double-labelling technique, using the fluorescent tracers True blue and Diamidino yellow. Although many tectal cells were single-labelled by injections into basilar pons or the cuneiform area, less than 5% were double-labelled. The two projections thus appear to arise mainly from separate populations of cells within the superior colliculus.

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Descending projections from the superior colliculus in rat: a study using orthograde transport of wheatgerm-agglutinin conjugated horseradish peroxidase.

Despite extensive behavioural work on the rat superior colliculus, its descending efferent pathways have not been fully characterised with modern anatomical tract-tracing techniques. To investigate these pathways, wheatgerm-agglutinin conjugated with horseradish peroxidase (1%) was injected at various locations within the superior colliculus of hooded rats. Label judged to be transported orthogradely was plotted on coronal sections modified from the atlas of Paxinos and Watson (1982). Two major descending pathways were identified. (i) The bulk of the fibres in the ipsilateral descending pathway leave the superior colliculus ventrolaterally, and course around the lateral margin of the midbrain reticular formation. Caudally, projecting fibres leave the main bundle to innervate the cuneiform nucleus, and parts of the pontomedullary reticular formation. Terminal fields associated with the major bundle of fibres are found in an area medial to the brachium of the inferior colliculus; the parabigeminal nucleus and adjacent tegmentum; the ventrolateral midbrain reticular formation; and the lateral pontine nuclei. (ii) The fibres of the main contralateral descending pathway leave the superior colliculus ventromedially, to cross midline in the dorsal tegmental decussation. They immediately turn caudally to join the predorsal bundle, in which they run the length of the brainstem to reach the cervical spinal cord. Major terminal fields occur in nucleus reticularis tegmenti pontis; the pedunculopontine/parabrachial area; paramedian pontomedullary reticular formation; and inferior olive. In addition there is lighter labelling in many areas of the pontomedullary reticular formation and in the cervical spinal cord. There was also a much sparser contralateral descending projection that crossed midline in the tectal commissure, and sent terminals to the contralateral cuneiform area and adjoining regions. These results suggest that the distribution of the descending efferent pathways from the superior colliculus in rats is similar to those described in other species. The fact that the two major pathways project to quite different terminal areas, together with previous findings that they have separate cells of origin within the tectum, suggests that they may also be functionally distinct.

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Tectal cells of origin of predorsal bundle in rat: location and segregation from ipsilateral descending pathway.

In rats, as in other mammals, one of the principal projections of the superior colliculus (SC) crosses the midline in the dorsal tegmental decussation to join the contralateral predorsal bundle (PDB). The cells of origin of this pathway were studied by injections of retrograde tracers (true blue or wheatgerm agglutinin-conjugated horseradish peroxidase) into the PDB rostral to its major fields of termination. Labelled cells were plotted with respect to fibre layers within the SC. The majority of labelled cells in the contralateral SC were located within the stratum album intermediale (SAI), between the fasciles oriented caudorostrally in that layer. They were of a wide range of sizes, and were much more numerous in lateral SC (where the SAI is broader) than in medial SC. The remaining labelled cells were found mainly in the deep layers. The effects of midline knife-cuts made prior to the injection of tracer suggested that most of the labelled SAI cells, but few of the deep-layer cells, projected across the midline in the dorsal tegmental decussation. Double-labelling procedures were used to investigate whether the cells of origin of the PDB send collaterals in the ipsilateral descending pathway of the SC. Injections of diamidino-yellow into the terminal regions of this pathway labelled very few PDB cells, although large numbers of other tectal cells were labelled. In contrast, extensive double labelling was observed after control injections of diamidino-yellow into the ipsilateral ascending pathway in the ventral diencephalon. These findings suggest that there is anatomical, and therefore perhaps functional, segregation of descending output channels from the superior colliculus in rat. This suggestion receives some support from comparison of the present results with those of tectal stimulation studies. Stimulation in the vicinity of lateral SAI gives contralaterally-directed head and body movements characteristic of orienting and approach, whereas stimulation in other tectal regions that contain predominantly the cells of origin of the ipsilateral descending pathway can give movements resembling avoidance or escape.

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Head and body movements produced by electrical stimulation of superior colliculus in rats: effects of interruption of crossed tectoreticulospinal pathway.

Stimulation of the superior colliculus in rats produces movements of the head and body that resemble either orientation and approach towards a contralateral stimulus, or avoidance of, or escape from, such a stimulus. A variety of evidence indicates that the crossed descending pathway, which runs in the contralateral predorsal bundle to the pontomedullary reticular formation and the spinal cord, is involved in orienting movements. The nature of this involvement was investigated, by assessing the effects on tectally-elicited movements of midbrain knife-cuts intended to section the pathway as it crosses midline in the dorsal tegmental decussation. As expected, ipsilateral movements resembling avoidance or escape were little affected by dorsal tegmental decussation section, whereas contralateral circling movements of the body were almost abolished. However, contralateral movements of the head in response to electrical stimulation were not eliminated, nor were orienting head movements to visual or tactile stimuli. There was some suggestion that section of the dorsal tegmental decussation increased the latency of head movements from electrical stimulation at lateral sites, and decreased the accuracy of orienting movements to sensory stimuli. These results support the view that the crossed tectoreticulospinal system is concerned with approach rather than avoidance movements. However, it appears that other, as yet unidentified, tectal efferent systems are also involved in orienting head movements. It is possible that this division of labour may reflect functional differences between various kinds of apparently similar orienting responses. One suggestion is that the tectoreticulospinal system is concerned less in open-loop orienting responses (that are initiated but not subsequently guided by sensory stimuli), than in following or pursuit movements.

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Movements resembling orientation or avoidance elicited by electrical stimulation of the superior colliculus in rats.

Some studies have reported that stimulation of the superior colliculus in rats produces orienting responses, as it does in a number of species. However, other studies have reported movements resembling avoidance and escape, which are not characteristic of collicular stimulation in other mammals. This apparent discrepancy was investigated by systematically recording the effects on head and body movements of electrical stimulation at a large number of sites throughout the superior colliculus (SC) and surrounding structures. It was found that the nature of the movements observed depended on the location of the stimulating electrode. Contralateral head and body movements resembling orienting and approach were obtained from sites in the intermediate and deep layers in rostral colliculus, the intermediate white layer and immediately surrounding tissue in central colliculus, and in all layers except deep white in caudal colliculus. At the remaining responsive sites, movements resembling avoidance and escape were obtained. The most common response was an ipsilateral cringelike movement of the body that developed into ipsilateral locomotion, followed by running and jumping as the current was increased. These movements were obtained from sites in the superficial and intermediate layers rostrally; from the intermediate gray and the medial superficial and deep layers in central colliculus; and from the deep layers and underlying tegmentum caudally. The distributions of sites, together with evidence from other studies, suggested the following conclusions: Within the superficial layers, avoidance responses were obtained from a region of the superior colliculus that appeared to represent the upper visual field, whereas orienting responses were obtained from a region apparently representing the lower visual field. Stimulation of the area containing the cells of origin of the predorsal bundle produced orientation and approach movements, whereas the avoidance and escape movements were probably mediated by parts of the ipsilateral descending pathway. The stimulation-induced avoidance and escape may reflect the importance of such responses to visual "events," particularly in the upper part of the visual field, in animals, like rats, with many predators.

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Detection of visual stimuli in far periphery by rats: possible role of superior colliculus.

Previous work has been shown that rats with lesions of the superior colliculus fail to respond to distracting visual stimuli presented in the peripheral field while the animals are running towards a central stimulus. To assess how far this peripheral neglect is due to an attentional deficit, rats were trained before operation to obtain reward by running towards either peripheral or central lights that were presented when the animals' heads were stationary in a known position. Response to stimuli presented 120 deg from the midline was severely impaired after removal of the superior colliculus: the animals behaved as if they had difficulty in detecting the onset of the light. In contrast, response to stimuli 40 deg from midline was unaffected. Control lesions of striate cortex did not significantly impair performance at any position. The finding that collicular animals were impaired at responding to stimuli in the far periphery, that were not irrelevant distractors but instead predicted reward, suggests that one component of the visual neglect produced by damage to the superior colliculus in rats may be a sensory deficit in the far peripheral field. In addition, comparison with previous results indicates that training to attend to visual stimuli in more central regions does improve performance, as would be expected if the deficit were an attentional one. It is therefore argued that collicular neglect in rats should be regarded as a multicomponent impairment.

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Tonic desynchronisation of cortical electroencephalogram by electrical and chemical stimulation of superior colliculus and surrounding structures in urethane-anaesthetised rats.

Damage to the superior colliculus in rats impairs desynchronisation of the cortical electroencephalogram in response to light flashes. However, it is unclear which elements within the superior colliculus, and which efferent collicular pathways, might be involved in alerting cerebral cortex to visual stimuli. To investigate this problem, the superior colliculus and surrounding structures were stimulated either electrically (3 s trains of 0.2 ms 100 Hz cathodal pulses), or chemically (200 nl of 5 mM sodium L-glutamate), in rats anaesthetised with urethane. The cortical electroencephalogram was recorded bilaterally from frontal cortex. At each site tested with electrical stimulation the threshold current (up to 60 microA) required to produce tonic desynchronisation (outlasting stimulation-offset by at least 10 s) was determined. Comparison of the effects of electrical and chemical stimulation suggested the following: (1) stimulation of cells in the deep layers of the superior colliculus can desynchronise the cortical electroencephalogram. There may also be an additional effective area in the rostral part of the superficial layers, but this needs to be confirmed in unanaesthetised animals. (2) Stimulation of fibres in the deep white layers of caudal superior colliculus, and of cells in a wide area of caudal midbrain reticular formation, are also effective at desynchronising the cortical electroencephalogram. It is therefore possible that the ipsilateral descending pathway, that runs from the superior colliculus to terminate in the parabigeminal and cuneiform nuclei and surrounding reticular formation, is involved in mediating cortical desynchronisation initiated by the superior colliculus. Evidence from other studies indicates that some sites in this pathway may be part of a "defence arousal system". (3) Sites on the ascending pathways from the superior colliculus, to structures including dorsal thalamus, pretectum, zona incerta and rostral midbrain reticular formation, were relatively ineffective at tonically desynchronising the cortex. However, some of these pathways might mediate phasic, movement-related arousal of collicular origin.

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Dissociation of stimulation-bound feeding and apomorphine-induced gnawing by lesions of superior colliculus.

The intense stereotyped gnawing induced by high doses of apomorphine is almost abolished by large bilateral lesions of the superior colliculus. It has been argued that the feeding produced by electrical stimulation of the lateral hypothalamic area is closely related to dopamine-mediated oral stereotypies; if so, it might be expected that lesions of the superior colliculus would also disrupt stimulation-bound feeding. Feeding was obtained from 14 hypothalamic electrodes in 8 hooded Lister rats. Subsequent electrolytic lesions of the superior colliculus had no overall effect on this behaviour from 13 of the 14 electrodes, even though the lesions reduced the gnawing induced by 8-20 mg/kg apomorphine to less than 10% of its preoperative intensity. It is concluded that stimulation-bound feeding and apomorphine-induced gnawing are not dependent on identical neural circuitry, and therefore stimulation-bound feeding is probably not mediated by the nigrotectal pathway.

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The superior colliculus and visual neglect in rat and hamster. I. Behavioural evidence.

Lesions of the superior colliculus in rats and hamsters produce a severe visual neglect. Three questions are asked concerning the nature of this impairment. Is the neglect a specific deficit, or part of a general disorder? It appears that the impairment is a relatively specific one, because, for example, collicular animals learn many visual discriminations as fast as controls. This pattern of behaviour leads to the second question. What is tested in neglect tasks but not in discrimination problems? Two answers have been proposed. (a) Orienting responses are required in tests of neglect but not in conventional visual-discrimination tasks. Accordingly, it has been suggested that damage to the superior colliculus interferes specifically with the orienting response. However, analysis of recent evidence indicates that rats and hamsters with collicular damage usually make no detectable response of any kind in tests of neglect, and that in some situations they do not respond to visual stimuli that produce a variety of behaviours in normal animals, such as freezing or fleeing, or activation of the EEG unaccompanied by any gross movement. Collicular neglect cannot therefore be explained solely as a response-specific impairment. (b) The stimuli used on tests of neglect are usually small, moving and presented in the peripheral visual field. In contrast, visual discriminanda are typically large, stationary and can be viewed with the central field. Recent experiments provide direct demonstrations that rats with lesions of the superior colliculus can orient to small flashing lights in central regions of the visual field, but unlike control animals may fail to respond if the lights are made dimmer, or are moved into the periphery. It appears that rats and hamsters with collicular damage fail to register particular kinds of visual stimulus. The final question concerns the nature of this stimulus-specific impairment: Do rats and hamsters with lesions of the superior colliculus neglect certain stimuli because, as has been proposed, they have difficulty in attending to the stimuli, or because they actually are incapable of detecting them? The fragmentary evidence currently available suggests that attentional factors are not important for stimuli that are very small, or that are presented in the far periphery of the visual field: such factors may be more important for large transient stimuli in the central field.(ABSTRACT TRUNCATED AT 400 WORDS)

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The superior colliculus and visual neglect in rat and hamster. II. Possible mechanisms.

The observations that removal of the superior colliculus in rats and hamsters produces a striking visual neglect, whereas damage to striate cortex does not, require explanation in terms of the anatomy and physiology of visual pathways in these animals. One proposal is that neglect is produced because the superior colliculus is the only visual structure directly concerned with the production of orienting movements. However, recent behavioural evidence indicates that this mechanism on its own is insufficient: collicular neglect is not confined to orienting movements, but is in part an inability to register particular kinds of visual stimulus. Two additional mechanisms are considered. The superior colliculus receives visual information that the geniculostriate pathway does not. A variety of anatomical and electrophysiological evidence suggests that this is the case. Although the exact nature of the information is unclear, there is some suggestion that the superior colliculus has a stronger representation of the peripheral field than the geniculostriate pathway, and may be more concerned with small transient stimuli throughout the visual field. An intact superior colliculus is essential for normal functioning of the geniculostriate system. Anatomical evidence indicates that there are pathways whereby: (a) visual cortex could use the superior colliculus as an output station; and (b) the superior colliculus could control signals entering or leaving the geniculostriate system, although the nature of the information carried by the pathways is not yet understood. The precise contribution of these two additional mechanisms to collicular neglect remains to be determined. However, it may be conjectured that the first would underly the deficit in stimulus detection that appears to be one component of collicular neglect, whereas the second mechanism might underly an attentional component.

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Superior colliculus and visual neglect in rat and hamster. III. Functional implications.

In comparison with the geniculostriate pathway, the retinotectal projection in rat and hamsters appears to emphasize information concerning localized transient stimuli, particularly in the periphery of the visual field. An important question is whether the superior colliculus merely relays this information elsewhere, or instead takes part in its analysis. This question is broken down into two parts. First, what decisions do rats and hamsters have to take concerning localized transient visual stimuli in the periphery? It is suggested that the following decisions are taken: (a) does the stimulus require any response? If the transient is self-produced, or is known on the basis of past experience to predict no important consequence, then it may be ignored; and (b) does the stimulus convey enough information to determine a response, either unlearnt (e.g. attack, flee, freeze) or learnt? If the stimulus appears to warrant some response, but it is not clear which, then it requires investigation. Second, what evidence is there that the superior colliculus participates in any of these decisions? It is argued on general grounds that the involvement of the superior colliculus in investigative orienting necessitates its knowing about the other decisions, since a useful orienting device cannot respond promiscuously to uninteresting or dangerous stimuli. This argument is supported by evidence from stimulation and recording studies, which in addition suggest that the superior colliculus is directly involved in producing a number of responses appropriate to peripheral transients, besides orienting. Thus, one function of the superior colliculus may be to help analyze and take decisions about localized transients in the periphery of the field.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗

Reduced locomotor activity as an acute effect of damage to superior colliculus in rats.

Rats with either electrolytic or radiofrequency lesions of the superior colliculus were tested in an open-field within 24 h of operation. They crossed significantly fewer squares and spent more time motionless then control animals, an effect that disappeared upon retesting 13 days later. Previously reported locomotor hyperactivity thus appears to be a chronic but not an acute effect of collicular damage in rats.

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Feeding induced by injections of muscimol into the substantia nigra of rats: unaffected by haloperidol but abolished by large lesions of the superior colliculus.

Intense activation of central dopamine systems has been associated with oral stereotyped behaviour, whereas less intense stimulation of these systems can increase feeding in non-deprived animals. There are several lines of evidence which suggest that the gamma-aminobutyric acid-containing striatonigral and nigrotectal projections are essential pathways mediating dopamine-related oral stereotypy. The present series of experiments was conducted to examine whether the same output route also mediates dopamine-related feeding. In the first experiment it was shown that bilateral injections of a sub-stereotypic dose of muscimol (0.05 nM) into the substantia nigra increased feeding of non-deprived rats. In Experiment II the feeding response was further characterised by demonstrating that food intake was initially suppressed for 30 min after which it was potentiated for 90 min. In Experiment III it was shown that a single dose of haloperidol (0.4 mg/kg), which was adequate to suppress overall food intake, was ineffective in preventing the increase in feeding produced by intranigral muscimol (0.05 nM). In contrast, it was demonstrated in Experiment IV that large lesions of the superior colliculus completely abolished the muscimol-induced increase in feeding. These results suggest that the striatonigral and nigrotectal projections may be important efferent pathways for both the oral stereotypy and the feeding responses linked with central dopamine transmission.

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Visual desynchronization of cortical EEG impaired by lesions of superior colliculus in rats.

It is unclear whether rats with lesions of the superior colliculus (SC) neglect visual stimuli because a) they fail to notice the stimuli or b) they notice the stimuli but fail to make specific orienting movements of the eyes and head toward them. To investigate this issue, we used an index of "noticing" that does not involve overt orienting movements, namely, desynchronization of the cortical electroencephalogram (EEG) in drowsy animals. In the first experiment, large collicular lesions with some invasion of surrounding areas severely impaired EEG desynchronization to a brief overhead flash of light but did not significantly affect desynchronization to brief bursts of white noise. No impairment was found after control lesions of cerebral cortex overlying the superior colliculus or of striate cortex. A subsequent experiment found that the visual impairment was still present when lesions were confined to the superior colliculus. It appears that rats with lesions of the superior colliculus can, in certain circumstances, fail to notice visual stimuli and that in rats, the superior colliculus is concerned not only with specific orienting movements to visual stimuli but also with visual desynchronization of the cortical EEG.

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Head-dipping by rats with lesions of superior colliculus during extended testing in hole-board.

It has previously been shown that rats with large lesions of the superior colliculus fail to head-dip during a 5 min hole-board test. To investigate whether this was a permanent deficit in exploratory behaviour arising from inability to produce the appropriate responses, collicular rats were tested in a hole-board for 60 min or more. The period before their first head-dip (mean 27 min 40 sec) was much longer than for unoperated animals (mean 22 sec), but subsequently the collicular rats showed a pattern of head-dipping that was similar (although not identical) to that of the control rats. It appears that rats with lesions of the superior colliculus are not permanently prevented from exploring the hole-board by inability to produce the required response, but rather that they may have difficulty in discovering certain features of novel environments.

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