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P Redgrave

Publications and source records attributed to P Redgrave.

At least 55 records · Page 3Linked to original sources
PubMed1992

Regional expression of fos-like immunoreactivity following seizures induced by pentylenetetrazole and maximal electroshock.

The expression of fos-like immunoreactivity (FLI) has been used widely as a marker of neural activation following the induction of seizures in several experimental models of epilepsy. The purpose of the present study was to provide a more detailed regional analysis of FLI expression following the induction of seizures by maximal electroshock (MES) and pentylenetetrazole (PTZ). Tonic-clonic seizures, matched for duration, were induced by MES applied by earclips (40 mA, 1 s) and intraperitoneal injections of PTZ (60 mg/kg); tonic hindlimb extension was present only after MES. Two hours after the induction of seizures brain tissue was processed for FLI. High levels of FLI were induced by both convulsion-inducing processes in a range of structures, including the dentate gyrus, the caudal amygdala, parts of the cerebral cortex, the bed nucleus of stria terminalis, various thalamic nuclei, the lateral parabranchial nucleus, and the nucleus of the solitary tract. In other structures, such as the medial and rostral amygdala, the ventromedial hypothalamic nucleus, the peripeduncular area, the central gray, and parts of the pretectum and superior colliculus, significantly greater FLI was induced by MES. Only in relatively few structures, such as the reticular thalamic nucleus and arcuate nucleus of the hypothalamus, did PTZ cause a much larger expression of FLI than MES. Insofar as the c-fos technique reflects neuronal activation, the present data reveal potentially important differences in the circuitry underlying the seizures induced in two major experimental models of epilepsy.

Animals↗
PubMed1992

Anticonvulsant role of nigrotectal projection in the maximal electroshock model of epilepsy--I. Mapping of dorsal midbrain with bicuculline.

Previous work has indicated that the anticonvulsant effect of nigral inactivation on the maximal electroshock model of generalized seizures is mediated by the projection from substantia nigra to superior colliculus. In accordance with this idea, and with the GABAergic nature of the nigrotectal pathway, microinjections of the GABAA antagonist bicuculline methiodide into the superior colliculus have been reported to block tonic hindlimb extension induced by maximal electroshock. To characterize the relevant circuitry more precisely, the present study sought to determine which region of the superior colliculus was important for the anticonvulsant effect of bicuculline by systematic mapping in the rat. Bilateral injections of bicuculline methiodide (50 pmol in 400 nl/side) were most effective in the caudal deep layers of the superior colliculus and adjoining midbrain reticular formation. These results suggest that the well-known projection from substantia nigra pars reticulata to the superior colliculus may not be involved in the anticonvulsant effect of nigral inactivation in the electroshock model, because this pathway terminates primarily in the intermediate layers of the superior colliculus throughout its rostrocaudal extent. Instead, some other pathway from ventral midbrain to a dorsal midbrain anticonvulsant zone appears to be part of the brain's anticonvulsant circuitry. The following paper [Redgrave et al. (1991) Neuroscience 46, 391-406] describes an anatomical study to characterize this pathway.

Animals↗
PubMed1992

Anticonvulsant role of nigrotectal projection in the maximal electroshock model of epilepsy--II. Pathways from substantia nigra pars lateralis and adjacent peripeduncular area to the dorsal midbrain.

Lesion evidence suggests that the superior colliculus is essential for mediating the anticonvulsant properties of nigral suppression in the electroshock model of epilepsy. However, our companion paper [Redgrave et al. (1991) Neuroscience 46, 379-390] established that the region of dorsal midbrain where bicuculline was most effective in suppressing tonic hindlimb extension did not correspond well with the known distribution of nigrotectal terminals. The purpose of the present anatomical study was, therefore, to investigate in more detail ventral midbrain connections to the dorsal midbrain anticonvulsant zone in rat. Small injections (10-20 nl) of a 1% solution of wheatgerm agglutinin conjugated with horseradish peroxidase were made specifically into the region of dorsal midbrain where bicuculline was maximally effective. Numerous retrogradely labelled cells were found in substantia nigra pars lateralis and adjacent peripeduncular area but not in substantia nigra pars reticulata. Retrogradely labelled cells were also located in ventral zona incerta. When wheatgerm agglutinin-horseradish peroxidase injections were made into lateral substantia nigra, a region of anterogradely transported reaction product characteristic of nerve terminals was observed in the caudolateral deep layers and underlying reticular tissue; this area corresponded well to the dorsal midbrain anticonvulsant zone. These data suggest that, in the electroshock model of epilepsy, direct connections between substantia nigra pars lateralis and adjacent peripeduncular area and the dorsal midbrain anticonvulsant zone could be critical for mediating the anticonvulsant properties previously attributed to substantia nigra pars reticulata. During the course of this study, anterograde projections from substantia nigra pars lateralis and adjacent peripeduncular area to both superficial and intermediate layers of the ipsilateral superior colliculus were noted. Additional experiments using retrograde transport of the fluorescent tracer Fast Blue confirmed these projections.

Amidines↗
PubMed1992

Topographical organization of the nigrotectal projection in rat: evidence for segregated channels.

Recent evidence suggests that projections from the superior colliculus to the brainstem in rat are organized into a series of anatomically segregated output channels. To understand how collicular function may be modified by the basal ganglia it is important to know whether particular output modules of the superior colliculus can be selectively influenced by input from substantia nigra. The purpose of the present study was, therefore, to examine in more detail topography within the nigrotectal system in the rat. Small injections (10-50 nl) of a 1% solution of wheatgerm agglutinin conjugated with horseradish peroxidase were made at different locations within substantia nigra and surrounding structures. A discontinuous puff-like pattern of anterogradely transported label was found in medial and caudal parts of the ipsilateral intermediate layers of the superior colliculus. In contrast, the rostrolateral enlargement of the intermediate layers contained a greater density of more evenly distributed terminal label. Injection sites associated with this dense pattern of laterally located label were concentrated in lateral pars reticulata, while the puff-like pattern was produced by injections into ventromedial pars reticulata. Retrograde tracing experiments with the fluorescent dyes True Blue and Fast Blue revealed that injections involving the rostrolateral intermediate layers were consistently associated with a restricted column of labelled cells in the dorsolateral part of ipsilateral pars reticulata. Comparable injections into medial and caudal regions of the superior colliculus produced retrograde labelling in ventral and medial parts of the rostral two-thirds of pars reticulata. Both anterograde and retrograde tracing data indicated that contralateral nigrotectal projections arise from cells located in ventral and medial pars reticulata. The present results suggest that the main ipsilateral projection from substantia nigra pars reticulata to the superior colliculus comprises two main components characterized by regionally segregated populations of output cells and spatially separated zones of termination. Of particular interest is the apparent close alignment between terminal zones of the nigrotectal channels and previously defined populations of crossed descending output cells in the superior colliculus. Thus, the rostrolateral intermediate layers contain a concentration of terminals specifically from dorsolateral pars reticulata and output cells which project to the contralateral caudal medulla and spinal cord. Conversely, the medial and caudal intermediate layers receive terminals from ventral and medial pars reticulata and contain cells which project specifically to contralateral regions of the paramedian pontine and medullary reticular formation.(ABSTRACT TRUNCATED AT 400 WORDS)

Amidines↗
PubMed1992

Use of a distracting task to obtain defensive head movements to looming visual stimuli by human adults in a laboratory setting.

Defensive responses to looming visual stimuli have been obtained in a wide variety of species, including human infants as young as one week. This phenomenon has not, however, been formally demonstrated for adults under laboratory conditions. In this paper it is reported that similar responses, namely avoidance movements of the head, can be obtained in most human adults provided that they are suitably distracted by playing a computer tracking game. Such behaviours were not obtained when subjects were not so distracted. The use of control conditions also ruled out the possibility that simple movement cues from stimuli presented on a noncollision trajectory are sufficient stimulus to obtain defensive responses. It is of interest to note that latencies for avoidance movements were significantly shorter than those for orienting movements in the same situation, but were no different from the latencies for orienting movements when subjects were not distracted. It is argued that these findings are consistent with the proposition that defensive head movements to looming stimuli, like orienting movements to novel peripheral stimuli, represent a basic visual competence that is normally suppressed (or subsumed) by higher competences. The decision to avoid is probably based on the computation of time to contact, and may reflect the operation of a subcortical system for elementary analysis of optic flow.

Adult↗
PubMed1991

Tectal induction of cortical arousal: evidence implicating multiple output pathways.

The rodent superior colliculus mediates a wide range of physiological and behavioural responses to sudden stimuli, including desynchronisation of the cortical electroencephalogram (EEG). To investigate how this desynchronisation is produced, one of two powerful excitatory agents, sodium L-glutamate (200 nl, 10 nmol) or bicuculline methiodide (200 nl, 40 pmol), was injected into the dorsal midbrain of sleeping rats. Microinjections at sites widely distributed throughout all layers of the superior colliculus were able to desynchronise the cortical EEG. i) In the superficial layers, bicuculline was effective at more sites than glutamate, whereas the reverse was true for the deep layers. ii) At some sites EEG desynchronisation occurred together with the defensive or orienting movements that are obtained from collicular stimulation in awake animals. At other sites cortical arousal occurred without such movements. iii) Comparison with a previous study suggested that urethane selectively blocks cortical arousal to glutamate injections in the superficial and intermediate grey layers. This evidence suggests that multiple collicular output pathways can desynchronise the cortical EEG, perhaps reflecting multiple functions for EEG desynchronisation.

Animals↗
PubMed1990

N-methyl D-aspartate (NMDA) evoked changes in blood pressure and heart rate from the rat superior colliculus.

Electrical stimulation and microinjections of the GABA antagonist bicuculline methiodide into the superior colliculus (SC) of the anaesthetized rat can evoke changes in blood pressure and heart rate. The long latency of bicuculline evoked responses, however, raises the possibility that they may have been produced by the diffusion of bicuculline to surrounding tissue, in particular, the periaqueductal gray. Thus, the purpose of the present study was to investigate whether such changes could have been produced by the activation of extracollicular neural elements. This was achieved by assessing the relative regional sensitivity of the SC and underlying structures (periaqueductal gray and dorsal tegmentum) with microinjections of the excitatory amino acid N-methyl D-aspartate (NMDA) for the production of short latency pressor responses. Dorsal midbrain injections of NMDA (200 nl of 100 mM) in the Saffan anaesthetized rat evoked clear short latency (single or double phase) increases in blood pressure accompanied in most cases by a longer latency increase in heart rate and respiration. Two regions within the dorsal midbrain contained significantly higher proportions of active sites compared with surrounding tissue: i) the superficial and intermediate layers of rostromedial SC, and ii) the caudal periaqueductal gray. The distribution of active sites indicated that pressor responses elicited from the rostromedial SC could not be explained by the diffusion of NMDA to underlying tissue. The question of whether the rostromedial SC might represent an early link in the circuitry responsible for organizing defensive movements and appropriate physiological changes to potentially dangerous overhead stimuli is considered.

Animals↗
PubMed1990

Output pathways from the rat superior colliculus mediating approach and avoidance have different sensory properties.

Neuroanatomical studies have demonstrated that the two major descending pathways from the superior colliculus arise from regionally segregated, distinct, cells of origin. Stimulation and lesion studies have implicated the crossed descending tecto-reticulo-spinal projection in approach movements towards novel stimuli whereas the ipsilateral pathway appears to be involved in the control of avoidance and escape-like behaviours. The present electrophysiological study attempted to characterise the sensory properties of antidromically identified cells of origin of these pathways in anaesthetised rats. We found that the contralaterally projecting predorsal bundle (PDB) efferents were primarily somatosensory while the ipsilateral cuneiform (CNF) projection was primarily visual. PDB cells, mainly found in the intermediate layers, responded principally to vibrissal stimulation with their overlying visual fields optimally stimulated by small dark moving objects in the lower rostral and lateral field. In contrast, most CNF cells were located rostromedially, with the greatest contribution from visual cells responsive to stimuli in the upper rostral field. A significant proportion of these showed no response to small moving dark discs but fired vigorously to 'looming' stimuli. Ethological considerations suggest that these are appropriate stimulus characteristics for a system controlling approach and avoidance behaviour in an animal such as the rat where predators generally appear from above and prey is found on the ground.

Afferent Pathways↗
PubMed1990

Organization of the crossed tecto-reticulo-spinal projection in rat--I. Anatomical evidence for separate output channels to the periabducens area and caudal medulla.

The superior colliculus has been used to study principles of sensorimotor transformation underlying the guidance of orienting movements by multimodal sensory stimuli. We have previously suggested that there may be two different classes of mechanism which can produce orienting-like movements towards a novel event; one that locates a stimulus on the basis of remembered position, and another which uses continuous feedback relating to target velocity. The crossed descending pathway of the superior colliculus is widely considered the projection most likely to relay signals associated with the production of orienting movements. However, if different neural mechanisms are used to produce functionally distinct types of orienting, we might expect this pathway to have separate anatomical components related to function. The purpose of the present experiment was to see if collicular fibres innervating two important pre-motor targets of the crossed descending pathway, the periabducens area and the caudal medulla-spinal cord, come from the same population of tectal cells. One of the retrogradely transported fluorescent tracers (Diamidino Yellow) was injected into the periabducens area, and another (True Blue or Fast Blue) was injected into tectospinal fibres at the level of the ventromedial caudal medulla. Under these conditions we found: (i) less than 10% of labelled cells within the superior colliculus contained both tracers; (ii) the bulk of singly labelled cells projecting to the periabducens area or the caudal medulla were concentrated at different locations within the colliculus, (iii) in regions of the superior colliculus where there was overlap of singly labelled cells, neurons projecting to the periabducens area or the caudal medulla could be distinguished morphologically. These data provide three classes of evidence which indicate that the crossed descending projection in rat can be subdivided into at least two relatively independent anatomical components. This conclusion may, in part, provide an anatomical substrate for the functional dissociations proposed for orienting movements.

Amidines↗
PubMed1990

Organization of the crossed tecto-reticulo-spinal projection in rat--II. Electrophysiological evidence for separate output channels to the periabducens area and caudal medulla.

The previous paper (Redgrave et al., Neuroscience 37, 571-584, 1990) presented anatomical evidence indicating there are at least two largely segregated components of the crossed tecto-reticulo-spinal pathway which project to the periabducens area and caudal medulla. An immediate question arising from this finding is whether tectal cells which project either to the periabducens area or to the caudal medulla have different electrophysiological response properties. An answer to this question would be relevant to the issue of whether different components of the tecto-reticulo-spinal system are specialized for the production of different classes of orienting movement. Accordingly, extracellularly recorded units in the superior colliculus of urethane anaesthetized rats were tested for antidromic activity following electrical stimulation of the periabducens area or the caudal medulla. When antidromic potentials were successfully recorded the sensory properties of the units were tested with a range of unimodal visual, somatosensory and auditory stimuli. The following results were obtained. (i) Tectal cells antidromically activated by stimulation of the caudal medulla were preferentially sensitive to somatosensory stimuli from the perioral region, while cells activated from the periabducens area were more frequently responsive to auditory stimuli. (ii) Tectal fibres activated by stimulation of the caudal medulla had significantly higher conduction velocities than the fibres activated by electrodes in the periabducens region. (iii) More than 90% of antidromically activated cells were located in stratum album intermediale or dorsal stratum profundum. These electrophysiological findings confirm and extend previous anatomical observations which indicate that components of the crossed descending projection of the colliculus may be functionally specialized for the production of different classes of orienting movements.

Acoustic Stimulation↗
PubMed1989

Event or emergency? Two response systems in the mammalian superior colliculus.

Recent studies of the effects of stimulating the superior colliculus (SC) in rodents suggest that this structure mediates at least two classes of response to novel sensory stimuli. One class contains the familiar orienting response, together with movements resembling tracking or pursuit, and appears appropriate for undefined sensory 'events'. The second class contains defensive movements such as avoidance or flight, together with cardiovascular changes, that would be appropriate for a sudden emergency such as the appearance of a predator, or of an object on collision course. The two response systems appear to depend on separate output projections, and are probably subject to different sensory and forebrain influences. These findings (1) suggest an explanation for the complex anatomical organization of the SC, with multiple output pathways differentially accessed by a very wide variety of inputs, (2) emphasize the similarities between the SC and the optic tectum in non-mammalian species, and (3) suggest that the SC may be useful as a model for studying both the sensory control of defensive responses, and how intelligent decisions can be taken about relatively simple sensory inputs.

Animals↗
PubMed1988

Intratectal glutamate suppresses pentylenetetrazole-induced spike-and-wave discharges.

Cortical spike-and-wave discharges evoked in rats by low (20-50 mg/kg) doses of subcutaneous pentylenetetrazole were suppressed by bilateral microinjection of sodium L-glutamate (100 mM, 200 nl/side) into the superior colliculus. Injections of saline into the superior colliculus, or glutamate into overlying cortex, were ineffective. This result is predicted by the hypothesis that the antiepileptic effects of nigral inactivation are at least partly mediated by the inhibitory nigrotectal pathway that runs from substantia nigra pars reticulata to the superior colliculus.

Animals↗
PubMed1988

Plasticity of behavioural response to repeated injection of glutamate in cuneiform area of rat.

Whereas a single microinjection of L-glutamate (10 nmol) into the cuneiform area of rats gives freezing, a second or third injection (delivered at 4-min intervals to the same site)can produce fast running. To examine whether this plasticity of response was caused by a simple increase in the amount of glutamate present, 30 nmol of glutamate were given in a single injection. In 93% of sites in the cuneiform area this procedure gave only freezing, although subsequent testing with repeated injections produced fast running in 53% of these sites. Thus, response potentiation to glutamate appears to require repeated stimulation, and may therefore be related to processes underlying the natural conditioning of defensive responses.

Animals↗
PubMed1988

The projection from superior colliculus to cuneiform area in the rat. I. Anatomical studies.

Although the ipsilateral descending pathway is a major output projection of the superior colliculus, little is known of its functions. We therefore carried out two studies to investigate in rats the part of the ipsilateral projection that terminates in an area ventral to the inferior colliculus, referred to as the cuneiform nucleus. The first study, described here, used orthograde and retrograde tract-tracing techniques to locate the cells of origin and precise region of termination of the tectocuneiform pathway. The main findings were as follows. Injections of WGA-HRP into the superior colliculus gave terminal label in the cuneiform nucleus and also in surrounding structures which included central grey, the midbrain tegmentum bordering the parabigeminal nucleus, and the external nucleus of the inferior colliculus. As well as the strong ipsilateral projection, there was a much weaker contralateral one which crossed the midline in the tectal commissure. Label in the cuneiform nucleus was heaviest after injections into the medial deep layers. However, no clear evidence was found for topography within the tectocuneiform projection: cuneiform label varied in intensity rather than pattern of distribution with variation in the collicular location of the injection site. Injections of retrograde tracers into the cuneiform are a labelled large numbers of collicular cells, which were distributed mainly in the deep and intermediate grey layers. In agreement with the data from orthograde tracing, the heaviest concentration of labelled cells was found in the medial deep layers. This concentration extended into the adjacent dorsolateral part of central grey. A similar distribution of labelled cells was seen after injections into the structures next to the cuneiform nucleus that also receive a tectal projection. Comparison of this distribution with that obtained from injections into other parts of the ipsilateral projection, including dorsolateral basilar pons, suggested that the projection to the cuneiform area may arise from a distinct set of collicular output cells. The projection from the superior colliculus to the cuneiform nucleus and immediately adjacent areas may therefore be also functionally distinct, mediating a particular kind of tectally-elicited response. The lack of clear topography in the projection suggests that this response may not have precise spatial direction.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

The projection from superior colliculus to cuneiform area in the rat. II. Defence-like responses to stimulation with glutamate in cuneiform nucleus and surrounding structures.

To investigate the role of the projection from superior colliculus to the cuneiform nucleus in mediating collicular responses, the cuneiform area (including the cuneiform nucleus and immediately adjacent structures such as caudal central grey) was stimulated in rats with microinjections of glutamate (50 mM, 200 nl, 10 nmole) and the animals' head and body movements observed. The most common responses obtained from sites in the cuneiform area were freezing, darting or fast running, the form or direction of which did not appear to be strongly influenced by the laterality of the injection. These responses were only a subset of those that have been obtained in previous studies from stimulation of the superior colliculus itself: stimulation of the cuneiform area did not give contralaterally directed movements resembling orienting or approach, or ipsilaterally directed movements resembling cringing or shying. It therefore appears that the tectocuneiform projection is likely to be involved only in some of the behaviours appropriate to unexpected stimuli that are mediated by the superior colliculus, namely undirected defensive responses elicited normally by certain kinds of threatening or noxious stimulation. Involvement with such responses would be consistent with an apparent lack of topography in the tectocuneiform projection, and the connections of the cuneiform nucleus with parts of the brain concerned with nociception (see previous paper). It is unclear, however, whether the somatic responses occur in parallel with, or as a result of, autonomic changes that have also been evoked by stimulation of the cuneiform area. One striking feature of stimulating the cuneiform area with glutamate was that at many sites the intensity of the response appeared to increase with successive (one to three) injections. It is possible that this plasticity of response, which can also be obtained from the superior colliculus itself, is related to processes involved in sensitisation or learning of defensive responses.

Animals↗
PubMed1988

Contralateral head movements produced by microinjection of glutamate into superior colliculus of rats: evidence for mediation by multiple output pathways.

One of the major efferent pathways of the superior colliculus crosses midline to run caudally in the contralateral predorsal bundle, innervating targets in the brain stem and eventually reaching the cervical spinal cord. A variety of evidence suggests that this tecto-reticulo-spinal pathway may mediate the orienting movements that can be evoked by tectal stimulation. However, we have recently found that orienting head movements can still be obtained in rats after section of the tecto-reticulo-spinal pathway, implying that additional pathways are also involved. The present study sought to test this implication, by taking advantage of the fact that in rats the cells of origin of the tecto-reticulo-spinal pathway are largely segregated within the lateral part of the stratum album intermediate. It is thus possible to find out whether orienting head movements can be produced by a cell-excitant from tectal regions that contain few cells of origin of the tecto-reticulo-spinal pathway. Hooded rats in an open field were filmed during microinjections of sodium L-glutamate (50 mM, 200 nl) into the superior colliculus, and the films analysed for the appearance of contralaterally directed movements of the head and body. Subsequent histological reconstruction of the injection sites indicated that such movements could be obtained from widespread areas within the superior colliculus, including not only lateral stratum album intermediale but also the deep layers, and parts of the medial superficial and intermediate layers. Moreover, sites in or close to lateral stratum album intermediate often gave circling movements with downward pointing head, whereas some sites outside lateral stratum album intermediale gave sustained immobility with the head pointing contralaterally and upwards. This evidence supports the view that tectal efferent pathways besides the tecto-reticulo-spinal pathway are involved in the control of head movement. In addition, at least some of these pathways are not collaterals of the tecto-reticulo-spinal pathway, since the movements were obtained from collicular regions with few tecto-reticulo-spinal pathway cells. Finally, the results are consistent with the view that different collicular output pathways mediate movements that have different functions.

Animals↗