High-level gait and balance disorders in the elderly: a midbrain disease?

The pathophysiology of gait and balance disorders in elderly people with 'higher level gait disorders' (HLGD) is poorly understood. In this study, we aimed to identify the brain networks involved in this disorder. Standardised clinical scores, biomechanical parameters of gait initiation and brain imaging data, including deep white matter lesions (DWML) and brain voxel-based morphometry analyses, were assessed in 20 HLGD patients in comparison to 20 age-matched controls. In comparison to controls, HLGD patients presented a near-normal preparatory phase of gait initiation, but a severe alteration of both locomotor and postural parameters of first-step execution, which was related to 'axial' hypokinetic-rigid signs. HLGD patients showed a significant grey matter reduction in the mesencephalic locomotor region (MLR) and the left primary motor cortex. This midbrain atrophy was related to the severity of clinical and neurophysiologically determined balance deficits. HLGD patients also showed a reduction in speed of gait, related to 'appendicular' hypokinetic-rigid signs and frontal-lobe-like cognitive deficits. These last two symptoms were correlated with the severity of DWML, found in 12/20 HLGD patients. In conclusion, these data suggest that the gait and balance deficits in HLGD mainly result from the lesion or dysfunction of the network linking the primary motor cortex and the MLR, brain regions known to be involved in the control of gait and balance, whereas cognitive and 'appendicular' hypokinetic-rigid signs mainly result from DWML that could be responsible for a dysfunction of the frontal cortico-basal ganglia loops.

[Gait and balance disorders in patients with atypical parkinsonian syndromes]. / Les troubles de la marche et de l'équilibre dans les syndromes parkinsoniens << plus >>.

The degenerative Parkinsonian "Plus" syndromes form a heterogeneous spectrum of pathologies comprising multiple system atrophy, progressive supranuclear palsy, Lewy body disease and cortico-basal degeneration. Their developmental profile is distinguished from that of Parkinson's disease by the early appearance of gait and balance disorders, isolated freezing of gait, primary progressive freezing of gait or an isolated or "pure" akinesia. The origin of these symptoms however remains poorly understood. The association of nigrostriatal dopamine neuron loss with either cortical lesions, in the case of cortico-basal degeneration and Lewy body disease, and/or of the brainstem, in the case of progressive supranuclear palsy, explains both the severity of the motor symptoms and the lack of, or minimal, improvement following levodopa therapy. Other symptomatic drug and surgical treatments have been proposed, but with generally disappointing results. Physiotherapeutic techniques targeting balance control can bring some temporary improvements.

Influence of sensory inputs and motor demands on the control of the centre of mass velocity during gait initiation in humans.

Human gait requires the simultaneous generation of goal-directed continuous movement (locomotion) and the maintenance of balance (postural control). In adults, the centre of mass (CoM) oscillates in the vertical plane while walking. During the single support phase of gait initiation, its vertical (vCoM) velocity increases as the CoM falls and is actively reversed prior to foot-contact. In this study we investigated whether this active control, which is thought to reflect balance control during gait initiation, is controlled by visual and somatosensory inputs (Experiment 1) and whether it is modified by a change in motor demands, two steps versus one step (Experiment 2). In all healthy adults, the vCoM velocity was braked, or controlled, by contraction of the soleus muscle of the stance leg. The elimination of visual input alone had no effect on braking, although its amplitude decreased when somatosensory inputs were disrupted (-47%), and further decreased when both visual and somatosensory inputs were disrupted (-83%). When subjects performed only one step, with no trailing of the stance foot, the vCoM velocity braking also decreased (-42%). These results suggest that active braking of the CoM fall during the transition to double support, an indicator of balance control, is influenced by both multisensory integration and the demands of the current motor program. The neural structures involved in this mechanism remain to be elucidated.

Gait and balance disorders in Parkinson's disease: impaired active braking of the fall of centre of gravity.

Gait and balance disorders are common in Parkinson's disease (PD), but its pathophysiology is still poorly understood. Step length, antero-posterior, and vertical velocities of the center of gravity (CG) during gait initiation were analyzed in 32 controls and 32 PD patients, with and without levodopa, using a force platform. Brain volumes and mesencephalic surface area were measured in PD patients. During the swing limb period, controls showed a fall in the CG, which was reversed before foot-contact indicating active braking of the CG fall. In PD patients, without levodopa, step length and velocity were significantly reduced and no braking occurred before foot-contact in 22 patients. With levodopa, step length and velocity increased in all patients and 7 patients improved their braking capacity. PD patients with normal braking (n = 17) had significantly lower gait and balance disorder scores and higher normalized-mesencephalic surface areas compared to patients with impaired braking (n = 15). The decreased step length and velocity, characteristic of PD, mainly result from degeneration of central dopaminergic systems. The markedly decreased braking capacity observed in half the PD patients contributes to their gait disorders and postural instability, perhaps as a result of nondopaminergic lesions, possibly at the mesencephalic level.

Effects of nigral stimulation on locomotion and postural stability in patients with Parkinson's disease.

The physiopathology of gait and balance disorders in Parkinson's disease patients is still poorly understood. Levodopa treatment and subthalamic nucleus (STN) stimulation improve step length and walking speed, with less effect on postural instability. These disorders have been linked to dysfunction of the descending basal ganglia outputs to brainstem structures. In this study, we evaluated the effects of stimulation of the substantia nigra pars reticulata (SNr), on locomotion and balance in Parkinson's disease patients. Biomechanical parameters and leg muscle activity were recorded during gait initiation in seven selected patients operated for bilateral STN stimulation, out of 204 stimulated patients, with one contact of each electrode located within the SNr. Step length, anteroposterior and vertical velocities of the centre of gravity were studied, with special reference to the subjects' ability to brake the centre of gravity fall before foot-contact, and compared to seven controls. In Parkinson's disease patients, five treatment conditions were tested: (i) no treatment, (ii) levodopa treatment, (iii) STN stimulation, (iv) SNr stimulation and (v) combined levodopa treatment and STN stimulation. The effects of these treatments on motor parkinsonian disability were assessed with the UPDRS III scale, separated into 'axial' (rising from chair, posture, postural stability and gait) and 'distal' scores. Whereas levodopa and/or STN stimulation improved 'axial' and 'distal' motor symptoms, SNr stimulation improved only the 'axial' symptoms. Compared to controls, untreated Parkinson's disease patients showed reduced step length and velocity, and poor braking just prior to foot-contact, with a decrease in both soleus (S) and anterior tibialis (AT) muscle activity. Step length and velocity significantly increased with levodopa treatment alone or in combination with STN stimulation in both natural and fast gait conditions, and with STN stimulation alone in the fast gait condition. Conversely, SNr stimulation had no significant effect on these measures in either condition. In the natural gait condition, no fall in the centre of gravity occurred as step length was low and active braking was unnecessary. In the fast gait condition, braking was improved with STN or SNr stimulation but not with levodopa treatment, with an increase in the stance leg S muscle activity. These results suggest that anteroposterior (length and velocity) and vertical (braking capacity) gait parameters are controlled by two distinct systems within the basal ganglia circuitry, representing respectively locomotion and balance. The SNr, a major basal ganglia output known to project to pontomesencephalic structures, is postulated as being particularly involved in balance control during gait.

Targeting the subthalamic nucleus for deep brain stimulation: technical approach and fusion of pre- and postoperative MR images to define accuracy of lead placement.

OBJECTIVES: To define the role of magnetic resonance imaging (MRI) and intraoperative electrophysiological recording in targeting the subthalamic nucleus (STN) in Parkinson's disease and to determine accuracy of electrode placement. PATIENTS AND METHODS: We implanted 54 electrodes into the STN in 27 patients. Target planning was done by coordinate guidelines and visualising the STN on MRI and defined in relation to the mid-point of the AC-PC line. Intraoperative microelectrode recording was used. We adjusted electrode positions for placement in the centre of the STN electrical activity and verified this on postoperative MRI in 16 cases, which were fused to the preoperative images to measure actual error in electrode placement in the three axes. RESULTS: Based on coordinate calculation and MRI localisation, the mean of the target was 11.5 mm lateral, 2.5 mm posterior and 4.1 mm inferior to the mid-point of the AC-PC line. Fifty good electrophysiological recordings of the STN (average length 4.65 mm) were achieved and target point adjusted in 90% of lead placements. The mean of the final target after electrophysiological correction was 11.7 mm lateral, 2.1 mm posterior, and 3.8 mm inferior to the mid-point. The distance from the centre of the electrode artefact to the final target used after electrophysiological recording on the fused images was 0.48 mm, 0.69 mm, and 2.9 mm in the x, y, and z axes, respectively. No postoperative MRI related complication was observed. CONCLUSION: Both direct visualisation of the STN on MRI and intraoperative electrophysiological recording are important in defining the best target. Individual variations exist in the location of the STN target. Fewer tracks were required to define STN activity on the side operated first. Our current stereotactic method of electrode placement is relatively accurate.

Phasic activation of substantia nigra and the ventral tegmental area by chemical stimulation of the superior colliculus: an electrophysiological investigation in the rat.

The source of short-latency visual input to midbrain dopaminergic (DA) neurons is not currently known; however, the superior colliculus (SC) is a subcortical visual structure which has response latencies consistently shorter than those recorded for DA neurons in substantia nigra and the ventral tegmental area. To test whether the SC represents a plausible route by which visual information may gain short latency access to the ventral midbrain, the present study examined whether experimental stimulation of the SC can influence the activity of midbrain DA neurons. In urethane-anaesthetized rats, 63 pairs of extracellular recordings were obtained from neurons in the SC and ipsilateral ventral midbrain, before and after local disinhibitory injections of the GABA antagonist bicuculline (20-40 ng/200-400 nL saline) into the SC. Neurons recorded from substantia nigra and the ventral tegmental area were classified as putative DA (25/63, 39.7%) or putative non-DA (38/63, 60.3%). In nearly half the cases (27/63, 42.8%), chemical stimulation of the SC evoked a corresponding increase in neural activity in the ventral midbrain. This excitatory effect did not distinguish between DA and non-DA neurons. In 6/63 cases (9.5%), SC activation elicited a reliable suppression of activity, while the remaining 30/63 cases (47.6%) were unaffected. In almost a third of cases (16/57, 28.1%) intense phasic activation of the SC was associated with correlated phasic activation of neurons in substantia nigra and the ventral tegmental area. These data suggest that the SC is in a position to play an important role in discriminating the appropriate stimulus qualities required to activate DA cells at short latency.

Superior colliculus projections to midline and intralaminar thalamic nuclei of the rat.

The superior colliculus (SC) projections to the midline and intralaminar thalamic nuclei were examined in the rat. The retrograde tracer cholera toxin beta (CTb) was injected into one of the midline thalamic nuclei-paraventricular, intermediodorsal, rhomboid, reuniens, submedius, mediodorsal, paratenial, anteroventral, caudal ventromedial, or parvicellular part of the ventral posteriomedial nucleus-or into one of the intralaminar thalamic nuclei-medial parafascicular, lateral parafascicular, central medial, paracentral, oval paracentral, or central lateral nucleus. After 10-14 days, the brains from these animals were processed histochemically, and the retrogradely labeled neurons in the SC were mapped. The lateral sector of the intermediate gray and white layers of the SC send axonal projections to the medial and lateral parafascicular, central lateral, paracentral, central medial, rhomboid, reuniens, and submedius nuclei. The medial sector of the intermediate and deep SC layers project to the parafascicular and central lateral thalamic nuclei. The paraventricular thalamic nucleus is innervated almost exclusively by the medial sectors of the deep SC layers. The superficial gray and optic layers of the SC do not project to any of these thalamic areas. The discussion focuses on the role these SC-thalamic inputs may have on forebrain circuits controlling orienting and defense (i.e., fight-or-flight) reactions.

Parallel analyses of nociceptive neurones in rat superior colliculus by using c-fos immunohistochemistry and electrophysiology under different conditions of anaesthesia.

Multiple sensory inputs to the superior colliculus (SC) play an important role in guiding head and eye movements toward or away from biologically significant stimuli. Much is now known about the visual, auditory, and somatosensory response properties of SC neurones that mediate these behavioural reactions. Rather less is known about the responses of SC neurones to noxious stimuli, and thus far, most of this information has been obtained in anaesthetised animals. Therefore, the purpose of the present study was to use the c-fos immunohistochemical technique and standard extracellular electrophysiology as parallel measures of nociceptive activity in the SC under different conditions of anaesthesia. In unanaesthetised animals, experimental and control treatments induced a qualitatively similar pattern of Fos-like immunoreactivity (FLI) in the SC, which was quantitatively related to the severity or biologic salience of the treatment; thus, baseline control < control injections of saline < a nonpainful stressor (immobilisation) < noxious injections of formalin. Compared with baseline levels, urethane and avertin anaesthesia induced FLI expression in the SC intermediate layers, although the FLI response to both noxious stimulation and control conditions was differentially suppressed in different layers of the SC by anaesthesia. Parallel electrophysiologic recordings found that anaesthesia was associated with high levels of spontaneous activity in the SC intermediate layers, often in neurones which were also nociceptive. High rates of background spike activity were also induced in the SC intermediate layers by noxious stimulation in chronically recorded awake animals. Although these results point to some differences between the nociceptive responses of SC neurones in anaesthetised and unanaesthetised animals, both data sets support the view that there are different populations of nociceptive neurones in the rodent SC that may be related to different adaptive functions of pain.

Cerebellar output exerts spatially organized influence on neural responses in the rat superior colliculus.

The deep cerebellar nuclei project to largely segregated target regions in the contralateral superior colliculus. Single-unit recordings have previously shown that nuclear inactivation normally suppresses spontaneously active collicular target neurons. However, facilitation of activity has also been found in a proportion of collicular units. In the present study we tested the hypothesis that the type of effect is related to the cerebellotectal topography. We recorded simultaneously in the deep cerebellar nuclei and superior colliculus of 53 anaesthetized rats. GABA microinjections produced a complete, reversible, arrest of activity in the deep cerebellar nuclei. We investigated the effect of this inactivation on 292 sensory and non-sensory cells in the collicular intermediate and deep layers. Of these, 29% showed a reduced response to their preferred sensory stimulus or decreased their spontaneous firing rate in the case of non-sensory cells. However, 15% increased their sensory responsiveness and/or spontaneous firing rate following cerebellar inactivation. No effect was seen in the remaining 56% of cells. The distribution of these different effects was highly significantly related to the topography of the cerebellotectal terminal fields. Thus, 68% of the suppressive effects were obtained from cells lying in the terminal fields of the deep cerebellar nucleus inactivated. Conversely, 86% of the excitatory effects and 66% of the cells showing no effect were obtained from cells falling outside the terminal field. The results support the view that the superior colliculus is an important site for the functional integration of primary sensory information, not only with cortical and basal ganglia afferents, but also with cerebellar information. The contrasting physiological responses observed within the terminal cerebellotectal topography appear to map closely on to the known distribution of the cells of origin of the two major descending output pathways of the superior colliculus and are possibly mediated by intrinsic inhibitory connections within its intermediate and deep layers. These results provide evidence for a neural architecture in the superior colliculus whose function is the selection of appropriate actions in response to novel stimuli and the suppression of competing motor programmes.

Spatial variation in the effects of inactivation of substantia nigra on neuronal activity in rat superior colliculus.

Superior colliculus (SC)-mediated behaviours are under the disinhibitory control of the striato-nigro-collicular projection. We systematically investigated the homogeneity of substantia nigra pars reticulata (SNr) influence on different populations of SC neurons by recording the effects of intranigral GABA microinjections on 149 cells at different locations in the rat SC. Suppression of the tonic activity of SNr resulted in both the facilitation and paradoxical inhibition of spatially-segregated SC target neurons. These dual influences were found to broadly map onto the SC origins of the descending projections known to support approach and avoidance/defensive behaviours. These findings are consistent with an organisation which promotes contrasting processes for the selection of a behaviour and simultaneous suppression of competing motor programs.

A floating microwire technique for multichannel chronic neural recording and stimulation in the awake freely moving rat.

We describe a cheap, and relatively simple, method for the construction and implantation of bundles of six fully-floating 25 microm microwire electrodes in the rat central nervous system (CNS). Wires are stiffened for implantation by temporarily attaching them to a micropipette guide with sucrose which subsequently dissolves in the brain. The associated headpiece connector mates with a plug-in FET which gives high quality recordings, free of movement artefacts, even when used with 3 m of unscreened cable. Different electrode configurations are easily selected and sufficient space is available on the headpiece to accommodate injection guide cannulae. The electrode performance was evaluated in 42 implanted rats where the system was used successfully for long term recording of superior colliculus (SC) deep layer neurons and behavioural responses evoked by electrical stimulation of the same wires. We obtained neural recordings on 81% of the 252 implanted wires, with 79% of these providing good, reliably discriminable, single unit responses following post-operative recovery. During a five-week testing period on a subsample of the 42 'best' electrodes (one per animal), we found the same sensory or motor response 1 week after initial testing in 91% wires, 67% after 2 weeks and 24% after 5 weeks. Using waveform templating techniques we were able to show that 62% of the electrodes still working at 5 weeks were reliably recording the same cell.

Cerebral vasomotion: a 0.1-Hz oscillation in reflected light imaging of neural activity.

Imaging of scattered and reflected light from the surface of neural structures can reveal the functional architecture within large populations of neurons. These techniques exploit, as one of the principal signal sources, reflectance changes produced by local variation in blood volume and oxygen saturation related to neural activity. We found that a major source of variability in the captured light signal is a pervasive low-frequency (0.1-Hz) oscillation which apparently results from regional cerebral blood flow. This signal is present in brain parenchyma as well as the microvasculature and exhibits many characteristics of the low-frequency "vasomotion" signals observed in peripheral microcirculation. Concurrent measurements in brain with a laser Doppler flow meter contained an almost identical low-frequency signal. The presence of the 0.1-Hz oscillation in the cerebral microcirculation could underlie a portion of the previously described characteristics reported in reflected-light imaging studies. The prevalence of the oscillatory phenomena in the brain raises substantial temporal sampling issues for optical imaging and for other visualization techniques which depend on changes in regional cerebral blood dynamics, such as functional magnetic resonance imaging.

Bicuculline-induced circling from the rat superior colliculus is blocked by GABA microinjection into the deep cerebellar nuclei.

In a recent electrophysiological experiment, we showed the deep cerebellar nuclei to be a major source of excitatory input to the superior colliculus. Furthermore, target neurons in the colliculus were found, in every case, to receive convergent tonic inhibitory input from the substantia nigra pars reticulata. In the present study, we investigated these effects in the awake rat. We asked whether circling behaviour, induced by unilateral injection of a GABA antagonist into the lateral colliculus, could be suppressed by concurrent cerebellar inactivation. Rats were chronically implanted with bilateral guide cannulae located above the superior colliculus and deep cerebellar nuclei. Bicuculline methiodide (25 pmol) was microinjected unilaterally into intermediate layers of the colliculus at increasing depths until an optimal contralateral circling response was elicited. This behaviour was taken as the "baseline response" and was the first of three treatments. The second was an identical manipulation of the colliculus with a concurrent 200-nl microinjection of 1 M GABA into the contralateral deep cerebellar nuclei. The third was a repeat of BIC alone into the colliculus or, if rotation had been suppressed by more than 50% on test 2, the treatment was collicular BIC plus deep cerebellar saline. This latter treatment was used as a control for possible non-pharmacological injection effects. The effect of cerebellar GABA at 26 sites (17 within cerebellar nuclei and 9 outside) on BIC-induced rotation at 15 collicular sites was studied in ten animals. Only GABA injections at sites that fell within the cerebellar nuclei significantly reduced turning (P < 0.0001). A full behavioural analysis showed that this was a specific suppression of turning, not the result of general motor impairment. These results provide clear behavioral evidence that opposing, convergent influences from the basal ganglia and cerebellum interact in the lateral superior colliculus to control head and body movements. They furthermore suggest that the tonic deep cerebellar excitation of the superior colliculus could be the driving force in the expression of rotation induced by manipulations of the basal ganglia.

Opposing excitatory and inhibitory influences from the cerebellum and basal ganglia converge on the superior colliculus: an electrophysiological investigation in the rat.

We recently showed (Westby et al., Eur. J. Neurosci., 5, 1378-1388, 1993) that the cerebellar interpositus nucleus is a source of excitatory drive for a population of spontaneously active neurons in the lateral intermediate layers of the contralateral superior colliculus. Anatomical and physiological studies have shown that this region of the colliculus contains cells of origin of the crossed descending tectoreticulospinal tract and receives GABAergic input from the ipsilateral basal ganglia. In the present study we tested the hypothesis that the same neurons receiving excitatory drive from the cerebellum also receive tonic inhibitory input from the substantia nigra pars reticulata. From a sample of 73 spontaneously active collicular cells we found that in 53% the firing rate was suppressed by GABA microinjection into the contralateral deep cerebellar nuclei; a further 15% showed a frequency increase. Of the collicular cells identified as receiving excitatory cerebellar input, 85% were found to be disinhibited by nigral GABA microinjection. The remainder were all inhibited by nigral GABA. These data show that the main excitatory influence from the cerebellum and the main inhibitory influence from the substantia nigra converge on at least one population of spontaneously active cells in the lateral intermediate layers of the superior colliculus. This finding is discussed in relation to the possible function of these spontaneous cells in movement control and nociception.

Excitatory drive from deep cerebellar neurons to the superior colliculus in the rat: an electrophysiological mapping study.

The cerebello-tectal projection arising from the interpositus nucleus was investigated electrophysiologically to test the hypothesis that the deep cerebellar nuclei constitute a source of tonic excitation in the superior colliculus. A total of 117 spontaneously active collicular neurons were recorded during GABA microinjection into 26 interpositus sites, where tonic single-cell deep cerebellar activity was also simultaneously recorded. GABA injection always led to suppression of interpositus activity, while in the colliculus a clear pattern of results emerged. 58% of superior colliculus cells showed no response to suppression of interpositus activity, 35% showed a frequency decrease and 7% showed a frequency increase. The majority of these responsive cells were found in a laterally located sheet of cells mainly restricted to the intermediate white layer, in close register with the known cells of origin of the predorsal bundle and completely overlapping the terminals of the nigrotectal pathway originating in dorsolateral substantia nigra pars reticulata. The implications of these results for cooperative theories of head movement control involving the superior colliculus, cerebellum and precerebellar nuclei are discussed.

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.

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.

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.