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.     

Control of recurrent inhibition of the lateral geniculate nucleus by afferents from the superior colliculus of the rabbit: a possible mechanism of saccadic suppression

Summary Stimulation of the ipsilateral superior colliculus elicited a short burst of discharges of the recurrent inhibitory interneurones in the geniculocortical pathway of the rabbit. The most effective stimulating sites for this excitation were located in the deep layers rather than the superficial layers of the superior colliculus. The short latency of the response (2.3±0.6 ms) implied an oligo-synaptic excitatory pathway from the deep layers of the superior colliculus to the recurrent interneurones located in the caudal reticular nucleus of the thalamus. Following the excitation of the inter-neurone, there was a prolonged inhibition which started 10–30 ms and ended 150 ms after the collicular stimulation. The maximal inhibition occurred 50–70 ms after the stimulation. The effects of collicular stimulation on the recurrent inhibitory interneurones may be concerned with the inhibition of the visual pathway during saccades and with the disinhibition of facilitation during fixation of a new visual target.     

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.     

Putative inhibitory collicular boutons contact large neurons and their dendrites in the dorsal cochlear nucleus of the rat

Within the circuits of the acoustic nuclei, the inferior colliculus sends descending (collicular) terminals to control with a feedback mechanism, part of the activity of the dorsal cochlear nucleus (DCN). It is not known whether this descending projection is prevalently excitatory or inhibitory. Using the neuronal tracer Wheat Germ Agglutinin conjugated to Horse Radish Peroxidase (WGA-HRP) the connections between the inferior colliculus and the DCN of the rat have been investigated. By far most retrograde labelled large neurons were glycine and GABA negative (pyramidal and giant neurons) and rare medium-size cells were glycine positive. The ultrastructural immunocytochemical analysis for glycine and GABA shows that mainly large, excitatory, neurons innervate the inferior colliculus. Rare medium-size glycine-positive cells with intermediate characteristics between pyramidal and cartwheel cells, seem also to project to the colliculus. Few WGA-HRP labelled boutons contact the large cells or their dendrites, have symmetric pre- and post-synaptic thickenings, contain pleomorphic and/or flat vesicles, and are labelled for GABA or glycine. Since no GABA labelled cells in both the dorsal and ventral cochlear nucleus were retrograde labelled from the colliculus, the source of these intrinsic anterograde labelled boutons must be external to the cochlear nucleus. GABA positive neurons are both present in the inferior colliculus (injected with the tracer) and superior olivary complex (not injected with the tracer). This suggests that the double labelled boutons (WGA-HRP and GABA) are inhibitory GABA-ergic collicular terminals contacting the excitatory neurons of the DCN. Other few boutons or mossy fibers containing round vesicles and immunonegative for both glycine and GABA, were also seen contacting the large neurons and their dendrites in the DCN. As the round vesicles boutons may be derived from other retrograde cells of the cochlear nucleus (pyramidal and stellate cells) and those glycine positive from the glycinergic neurons in paraolivary nuclei, it is more likely that only the WGA-HRP and GABA labelled boutons are true collicular terminals.     

The fixation area of the cat superior colliculus: effects of electrical stimulation and direct connection with brainstem omnipause neurons

The superior colliculus has long been recognized as an important structure in the generation of saccadic displacements of the visual axis. Neurons with presaccadic activity encoding saccade vectors are topographically organized and form a motor map. Recently, neurons with fixation-related activity have been recorded at the collicular rostral pole, at the area centralis representation or fixation area. Another collicular function which deals with the maintenance of fixation behavior by means of active inhibition of orientation commands was then suggested. We tested that hypothesis as it relates to the suppression of gaze saccades (gaze = eye in space = eye in head + head in space) in the head-free cat by increasing the activity of the fixation cells at the rostral pole with electrical microstimulation. Long stimulation trains applied before gaze saccades delayed their initiation. Short stimuli, delivered during the gaze saccades, transiently interrupted both eye and head components. These results provide further support for a role in fixation behavior for collicular fixation neurons. Brainstem omnipause neurons also exhibit fixation-related activity and have been shown to receive a direct excitatory input from the superior colliculus. To determine whether the collicular projection to omnipause neurons arises from the fixation area, the deep layers of the superior colliculus were electrically stimulated either at the rostral pole including the fixation area or in more caudal regions where stimulation evokes orienting responses. Forty-nine neurons were examined in three cats. 61% of the neurons were found to be orthodromically excited by single-pulse stimulation of the rostral pole, whereas only 29% responded to caudal stimulation. In addition, stimuli delivered to the rostral pole activated, on average, omnipause neurons at shorter latencies and with lower currents than those applied in caudal regions. These results suggest that excitatory inputs to omnipause neurons from the superior colliculus are principally provided by the fixation area, via which the superior colliculus could play a role in suppression of gaze shifts.     

Evidence for the participation of nigrotectal γ-aminobutyrate-containing neurones in striatal and nigral-derived circling in the rat

The γ-aminobutyrate-containing nature of nigrotectal neurones and the possible involvement of the tectum in circling behaviour were investigated in the rat. Electrolytic or kainic acid lesions of the substantia nigra reduced γ-aminobutyrate levels on average by 19–29% in intermediate and deep, but not superficial superior colliculus. Placement of lesions or injection of muscimol (40 ng) into these γ-aminobutyrate-innervated layers of superior colliculus gave only weak ipsilateral posturing or circling that was intensified by apomorphine, but which strongly antagonized contraversive apomorphine-induced circling in 6-hydroxydopamine pretreated rats (lateral > medial sites). Contraversive circling to unilateral intranigral muscimol (40 ng) was significantly attenuated by lesions or muscimol injections placed in the ipsi- or contralateral superior colliculus. Picrotoxin (40 ng) and tetanus toxin (30 mouse LD₅₀ doses) evoked explosive motor behaviour from medial colliculus and vigorous contraversive circling when injected into the lateral colliculus. The latter offset ipsiversive asymmetries to kainate (0.8 μg) in the corresponding substantia nigra. Bilateral intratectal picrotoxin produced hyperactivity that reversed haloperidol catalepsy. Similar bilateral administration of muscimol did not produce catalepsy but a state of frozen immobility. Kainic acid introduced into the superior colliculus gave mixed excitatory-inhibitory responses initially followed by ipsiversive circling only and loss of tectal perikarya. None of these drug effects occurred from the overlying cerebral cortex or subjacent tegmentum.We propose that separate medial ‘non-postural’ and lateral ‘postural’ tectal locomotor regions may exist in the superior colliculus that are situated within a striato-nigrotectal outflow system capable of influencing the animal's motor activity and posture.     

Immunocytochemical evidence for the involvement of glycine in sensory centers of the rat brain.

Glycine-like immunoreactivity was localized to a number of sites in the rat brain which are involved in processing sensory information. In the auditory and vestibular systems, glycine immunoreactivity was seen in dorsal and ventral cochlear nuclei, superior olive, trapezoid body, medial and lateral vestibular nuclei, and inferior colliculus. Staining in the visual system was seen in retina, dorsal lateral geniculate nucleus, and superior colliculus. The olfactory system exhibited staining in the olfactory bulb and accessory olfactory formation. Somatosensory centers with glycine immunoreactivity included the dorsal column nuclei, spinal trigeminal nucleus, principal sensory nucleus of V, reticular formation, and periaqueductal gray. Glycine-immunoreactive neurons were also seen in cerebellar cortex, deep cerebellar nuclei, hippocampus, cerebral cortex, and striatum. The distribution of staining indicates that glycine plays a major role in sensory centers with actions at both strychnine-sensitive and strychnine-insensitive receptors.     

Firing properties of preposito-collicular neurones related to horizontal eye movements in the alert cat

The projection from the nucleus prepositus hypoglossi (PH) to the superior colliculus (SC) has been proposed to provide a feedback control of collicular saccadic activities. The present study aimed to identify the functional properties of PH neurones projecting to the SC relative to eye movement parameters. Preposito-collicular neurones were identified in alert cats by antidromic invasion and collision tests following electrical stimulations of the contralateral SC. Their discharges were then correlated with the horizontal component of eye movements. Particular attention was given to the timing of discharges relative to saccade onsets. Most prepositocollicular neurones (12/14) displayed transient activities associated to eye velocity, and onsets preceded the saccade onset by 9.4–19.9 ms. The mean eye velocity sensitivity of these early preposito-collicular neurones (1.46±0.53 spikes/s per degree per second) was quite similar to that calculated from a sample of putative motoneurones or interneurones that have been recorded within abducens nucleus and quantified in the same conditions. The remaining two preposito-collicular neurones exhibited transient activity related to saccades, but this followed the transient putative motoneuronal discharge. These delayed neurones also had lower eye velocity sensitivities (0.38 sp/s per degree per second and 0.58 sp/s per degree per second, respectively) compared with early neurones. Both classes of preposito-collicular neurones also displayed a subsequent tonic activity correlated with the eye position. Taken together, these results demonstrate that preposito-collicular neurones code both eye position and eye velocity just like ocular motoneurones, but in a predictive manner. The anticipatory discharge of early neurones makes them likely candidates for the control of peak activities of saccade-related collicular neurones, particularly in the caudal colliculus. Delayed preposito-collicular neurones may also participate in the control of collicular activities, but probably in more rostral SC, where peak activities occur later during eye movements together with smaller motor error coding.     

Nigral and cerebellar synaptic terminals in the intermediate and deep layers of the cat superior colliculus revealed by lesioning studies

The presence of degenerating nigral and cerebellar synaptic terminals in the intermediate and deep layers of the cat superior colliculus was demonstrated by electron microscopy following lesions of the substantia nigra or brachium conjunctivum. The superior colliculus was taken for analysis 4–5 days after operation. Nigral terminals underwent a dark type of degeneration following kainic acid lesion of the pars reticulata of the substantia nigra. The majority of nigral degenerating terminals and axons were found in the stratum griseum intermediate with a few in the stratum griseum profundum. Two kinds of cerebellar terminals were distinguished by general appearances such as size, type of synaptic contact and type of synaptic vesicle and by the pattern of degenerative changes following electrical lesion of the brachium conjunctivum. Large elongated synaptic terminals 4–7 μm in diameter, were found mainly in the stratum griseum profundum. They often had double termination with conventional dendrites and with vesicles containing dendrites. This kind of terminal had a filamentous type of degeneration. A second type of degenerating cerebellar terminal, characterized by an electron-lucent type of degeneration, was predominantly located in the stratum griseum intermediale. These terminals were circular, about 4 μm in diameter, and did not have synaptic contact with vesicle-containing profiles. The finding of the two types of degenerating terminal after lesion of the brachium conjunctivum can be considered as evidence of the coexistence of at least two kinds of cerebellar terminals in the superior colliculus. The presence of nigral and cerebellar terminals in the intermediate and deep layers of the superior colliculus implicates the involvement of the substantia nigra and cerebellum in control of collicular visuomotor function.     

Intraparenchymal grafting of cerebellar cell suspensions to the deep cerebellar nuclei of pcd mutant mice, with particular emphasis on re-establishment of a Purkinje cell cortico-nuclear projection.

Summary In transplanting embryonic cerebellar grafts to the cerebellar cortex of Purkinje cell degeneration (pcd) mutant mice to replace missing Purkinje cells (PC), donor PC leave the graft and migrate to the molecular layer of the host. However, PC axons do not always reach the deep cerebellar nuclei of the host, which would be a key element in restoring much of the necessary inhibitory cortico-nuclear projection associated with normal cerebellar function. Rather, grafted PC axons often innervate a region containing deep cerebellar nuclei neurons inside the transplant, while the perikaryon migrates to the host molecular layer. In the present study, aimed at re-establishing a PC innervation of the deep nuclei, we implanted E12 cerebellar cell suspensions intraparenchymally to the deep cerebellar mass of the hosts. The development of grafted PC was monitored with 28-kDa calcium-binding protein (CaBP) immunocytochemistry at various times after transplantation. At short survival times (5 days after grafting), grafts were confined to the site of the original injection. At longer survival times (7–32 days after grafting), grafted PC formed a migratory stream that reached the cerebellar cortex of the host. The most robust graft development was seen 1 month after grafting, the longest survival time allowed in this series of experiments. At that time, clusters of donor PC were found both in the deep nuclei parenchyma and aligned along cortical folia. The orientation of the dendritic trees of PC that had migrated to the cortex was toward the pia. A CaBP-immunoreactive fibre plexus innervated the host deep cerebellar nuclei. The stream of grafted PC extended from the deep cerebellar nuclei to the cerebellar cortex of the host, indicating that donor PC could establish their axonal contacts in the deep nuclei and then move to their final cortical locality, thus recapitulating a migratory path normally taken during cerebellar ontogeny. It appears therefore that both from the pathophysiological and ontogenetic standpoints, the deep cerebellar nuclei represent the appropriate site for PC implantation in cerebellocortical atrophy.     

Colocalization of neurotransmitters in the deep cerebellar nuclei

Summary An abundance of glycine and glycine receptor immunoreactivities was found in all three parts of the deep cerebellar nuclei. Glycine immunoreactivity was restricted to small neurons throughout most of the deep cerebellar nuclei except for a few large positive neurons in the ventral part of the fastigial nuclei. In addition, glycine immunoreactivity was found in boutons outlining somata of large glycine negative neurons. Complementary to the glycine positive boutons was an intense glycine receptor immunoreactivity on large deep cerebellar nuclei neurons. Comparisons of immunoreactivities for glycine, GABA and aspartate in consecutive one micron sections revealed that many small neurons colocalized glycine and GABA, while some large neurons in the fastigal region colocalized glycine and aspartate.Ultrastructural investigations revealed glycine receptors on postsynaptic sites of dendrites and somata. Most boutons, which were presynaptic to glycine receptor sites, were filled with small flattened vesicles; however, a small percentage of boutons had round clear or dense core vesicles. Frequently, each bouton apposed multiple active zones on the dendrite or soma. One of these active zones was positive for glycine receptor and another was negative.This study supports: (1) glycine as a neurotransmitter in deep cerebellar nuclei, and (2) glycine and GABA colocalization in the same cell and bouton, but releasing to different receptor sites on the target neuron. Furthermore, the coexistence of glycine with GABA in the same deep cerebellar neuron may play an important role in controlling the conset and duration of signal transmission.     

Neural control of vocalization in bats: mapping of brainstem areas with electrical microstimulation eliciting species-specific echolocation calls in the rufous horseshoe bat

Summary 1. The functional role of brainstem structures in the emission of echolocation calls was investigated in the rufous horseshoe bat, Rhinolophus rouxi, with electrical low-current microstimulation procedures. 2. Vocalizations without temporal and/or spectral distortions could be consistently elicited at low threshold currents (typically below 10 A) within three clearly circumscribed brainstem areas, namely, the deep layers and ventral parts of the intermediate layers of the superior colliculus (SC), the deep mesencephalic nucleus (NMP) in the dorsal and lateral midbrain reticular formation and in a distinct area medial to the rostral parts of the dorsal nucleus of the lateral lemniscus. The mean latencies in the three vocal areas between the start of the electrical stimulus and the elicited vocalizations were 47 msec, 38 msec and 31 msec, respectively. 3. In pontine regions and the cuneiform nucleus adjacent to these three vocal areas, thresholds for eliciting vocalizations were also low, but the vocalizations showed temporal and/or spectral distortions and were often accompanied or followed by arousal of the animal. 4. Stimulus intensity systematically influenced vocalization parameters at only a few brain sites. In the caudo-ventra1 portions of the deep superior colliculus the sound pressure level of the vocalizations systematically increased with stimulus intensity. Bursts of multiple vocalizations were induced at locations ventral to the rostral parts of the cuneiform nucleus. No stimulus-intensity dependent frequency changes of the emitted vocalizations were observed. 5. The respiratory cycle was synchronized to the electrical stimuli in all regions where vocalizations could be elicited as well as in more ventrally and medially adjacent areas not yielding vocalizations on stimulation. 6. The possible functional involvement of the vocal structures in the audio-vocal feedback system of the Dopplercompensating horseshoe bat is discussed.Abbreviations AP pretectal area - BIC brachium of the inferior colliculus - CM mamillary body - CTm medial trapezoid body - CUN cuneiform ncl - HYP hypothalamus - IC (rp) inferior colliculus (rostral pole) - IP interpeduncular ncl. - LL (v, i, d) lateral lemniscus (ventral, intermediate, dorsal) - MGB medial geniculate body - NMP deep mesencephalic nucleus - NR red nucleus - P pons - PAG periaqueductal gray - PC cerebral peduncle - PO pons oralis - RD raphe dorsalis - RRF retrorubral field - RTP ncl. reticularis pontis - SC (s, i, d) superior colliculus (superficial, intermediate, deep) - SG suprageniculate ncl - SN substantia nigra - 3 ncl. of the oculomotor nerve     

Nigrotectal projections in the primate Galago crassicaudatus

Summary The pattern of the nigrotectal projection in Galago crassicaudatus was determined using retrograde and anterograde transport methods. These experiments revealed that pars reticulata and pars lateralis of the substantia nigra project to all layers of the ipsilateral and contralateral superior colliculus, except to layer I. The nigrotectal projection is not homogeneous, but is concentrated in particular collicular layers and sublayers, and the intensity and laminar distribution of the projection varies along the rostral-caudal dimension of the superior colliculus. The ipsilateral and contralateral nigrotectal projections are generally similar, except that a tier of dense label which is prominent in the ventral part of much of the ipsilateral layer IV is not obvious contralaterally; moreover, the contralateral projection is much sparser than the ipsilateral. Deposits of tracers at different medial-lateral locations within the substantia nigra did not result in different laminar patterns of anterogradely transported label in the superior colliculus. Based on the known connections and functions of the collicular layers and sublayers, the pattern and distribution of the nigrotectal projection suggests that the substantia nigra may use this pathway to gain access to particular components of vision- and visuomotor-related networks.Abbreviations Cd Caudate - CG Central gray - CP Cerebral peduncle - D Dorsal - FEF Frontal eye field - IC Internal capsule - ICo Inferior colliculus - IP Interpeduncular nucleus - L Lateral - LG Lateral geniculate - MDmf Medial dorsal nucleus, pars multiformis - MG Medial geniculate - MI Mammillary body, lateral nucleus - Mm Mammillary body, medial nucleus - MRF Mesencephalic reticular formation - nIII Oculomotor nerve - OT Optic tract - PG Pontine gray - Pg Pregeniculate nucleus - Pt Pretectal complex - Pulv Pulvinar nuclei - Put Putamen - R Red nucleus rostral - SCi,d Superior colliculus, intermediate and deep layers - SCs Superior colliculus, superficial layers - SEF Supplementary eye field - SNc Substantia nigra, pars compacta - SNr Substantia nigra, pars reticulata - SNr, 1 Substantia nigra, pars reticulata and pars lateralis - St Subthalamic nucleus - VAmc Ventral anterior nucleus, pars magnocellularis - V Cort Visual cortical areas - ZI Zona incerta - II Layer II of the superior colliculus - III Layer III of the superior colliculus - IV Layer IV of the superior colliculus - V Layer V of the superior colliculus - VI Layer VI of the superior colliculus     

The cerebellar projections to the superior colliculus and pretectum in the cat: An autoradiographic and horseradish peroxidase study

Efferent projections from the cerebellar nuclei to the superior colliculus and the pretectum have been studied using both retrograde and orthograde labeling techniques in the cat. In order to identify what parts of the cerebellar nuclei project to the superior colliculus and the pretectum, the retrograde horseradish labeling technique was employed. In another set of experiments, tritiated amino acids were injected into each of the cerebellar regions from which the cerebello-tectal and cerebellopretectal projections arise, and the laminar and spatial distributions of orthograde labeling in the superior colliculus and the pretectum were compared.The results showed that the cerebello-tectal projections arise from two different regions of the cerebellar nuclei: the caudal half of the medial nucleus and the ventrolateral part of the posterior interposed nucleus. Fibers arising from the medial nucleus distribute bilaterally in the superficial zone of the intermediate gray layer in the superior colliculus, while those originating from the posterior interposed nucleus terminate contralaterally in the deeper aspect of the intermediate gray layer and in the deep gray and white layers. Although the lateral nucleus does not contribute to the cerebello-tectal projection, it projects profusely to the pretectum contralaterally. The origin of the cerebello-pretectal projection lies in the parvicellular part of the lateral nucleus. Among several pretectal nuclei, the posterior pretectal, the medial pretectal nucleus and the reticular part of the anterior pretectal nucleus receive the cerebellar afferents.The findings of the differential projections from the cerebellum to the superior colliculus and the pretectum suggest that the cerebellum exerts a regulatory influence on visuo-motor and somato-motor transfer in these midbrain structures by differential circuits.     

Nociceptive responses of midbrain dopaminergic neurones are modulated by the superior colliculus in the rat

Midbrain dopaminergic neurones exhibit a short-latency phasic response to unexpected, biologically salient stimuli. In the rat, the superior colliculus is critical for relaying short-latency visual information to dopaminergic neurones. Since both collicular and dopaminergic neurones are also responsive to noxious stimuli, we examined whether the superior colliculus plays a more general role in the transmission of short-latency sensory information to the ventral midbrain. We therefore tested whether the superior colliculus is a critical relay for nociceptive input to midbrain dopaminergic neurones. Simultaneous recordings were made from collicular and dopaminergic neurones in the anesthetized rat, during the application of noxious stimuli (footshock). Most collicular neurones exhibited a short-latency, short duration excitation to footshock. The majority of dopaminergic neurones (92/110; 84%) also showed a short-latency phasic response to the stimulus. Of these, 79/92 (86%) responded with an initial inhibition and the remaining 14/92 (14%) responded with an excitation. Response latencies of dopaminergic neurones were reliably longer than those of collicular neurones. Tonic suppression of collicular activity by an intracollicular injection of the local anesthetic lidocaine reduced the latency, increased the duration but reduced the magnitude of the phasic inhibitory dopaminergic response. These changes were accompanied by a decrease in the baseline firing rate of dopaminergic neurones. Activation of the superior colliculus by the local injections of the GABA(A) antagonist bicuculline also reduced the latency of inhibitory nociceptive responses of dopaminergic neurones, which was accompanied by an increased in baseline dopaminergic firing. Aspiration of the ipsilateral superior colliculus failed to alter the nociceptive response characteristics of dopaminergic neurones although fewer nociceptive neurones were encountered after the lesions. Together these results suggest that the superior colliculus can modulate both the baseline activity of dopaminergic neurones and their phasic responses to noxious events. However, the superior colliculus is unlikely to be the primary source of nociceptive sensory input to the ventral midbrain.     

Alterations of neuronal activity in the superior colliculus of rotating animals

We have investigated the relationship between alterations in neuronal activity in the superior colliculus and behavioral responses which occur following disruption of basal ganglia circuitry. These changes were analysed following unilateral suppression of the immediate early genes, c-fos and ngfi-a, in the striatum and/or the globus pallidus. Animals with unilateral suppression of immediate early gene expression in the striatum exhibited robust circling activity, following administration of D-amphetamine, that was directed towards the side of suppression. The intensity of rotation was inversely related to the length of the recovery period following antisense infusion and increased significantly when the globus pallidus was infused simultaneously with the striatum. The difference between ipsiversive (towards the antisense-infused hemisphere) and contraversive rotations was calculated and animals were grouped by number according to their ipsiversive bias: I, <50 turns; II, 50-500 turns; III, 500-1000 turns; IV, >1000 turns. Immunohistochemical localization of Fos was used as an indicator of neuronal activity in the superior colliculus. While group I animals showed diffuse Fos-like immunoreactivity throughout the intermediate layers of the superior colliculus, those animals in groups II-IV showed increasing suppression of Fos-like immunoreactivity in the stratum album intermediale and marked enhancement in the stratum griseum intermediale. Correlation and regression analysis revealed a significant positive relationship between the number of ipsiversive rotations and the number of Fos-positive nuclei in the stratum griseum intermediale of the ipsilateral superior colliculus. These data suggest that the degree of rotation elicited in an animal may depend on reciprocal suppression/stimulation of adjacent intermediate strata of the superior colliculus. This study provides the first demonstration, using Fos immunohistochemistry, of changes in tectal activity produced by alterations in basal ganglia function. These findings support previous electrophysiological studies in this region and suggest that the nigrotectal projection may be an important site of altered basal ganglia output.     

Sensory responses of intralaminar thalamic neurons activated by the superior colliculus

Summary The intralaminar thalamus of anesthetized rats was explored for neurons activated by stimulation of the superior colliculus and responsive to sensory inputs. Neurons activated by stimulation of the intermediate and deep collicular layers were distributed throughout the intralaminar thalamus. Approximately one half of them responded to tectal as well as sensory inputs. The majority were nociceptive or had a more complex response pattern including responses to auditory stimulation. A smaller population of low threshold units had contralateral orofacial receptive fields and responded to light taps; these units were preferentially localized anteriorly in the central lateral and paracentral nuclei. Neurons responsive to tectal and sensory stimulation were randomly intermingled with other neurons which had no detectable sensory input. The results indicate that ascending projection neurons of the intermediate and deep layers of the superior colliculus provide an input to functionally diverse subpopulations of intralaminar thalamic neurons. In view of its projections to motor cortex and basal ganglia, the intralaminar thalamus appears directly implicated in basal ganglia and superior colliculus related mechanisms of attention, arousal and postural orienting.     

Projections of extraocular, neck muscle, and retinal afferents to superior colliculus in the cat: their connections to cells of origin of tectospinal tract.

Unit recordings were made in the superior colliculus of cats anesthetized with chloralose and with Pentothal. Electrical stimulation of extraocular muscle afferents and neck muscle afferents excited more units in the superior colliculus than did a variety of moving and stationary visual stimuli. Units responding to neck muscle afferent stimulation fell into three populations; one population firing with a short latency and following stimulus presentation up to 1/s, a second population with a long latency and following stimulus presentation at frequencies lower than 15/min, and a third population exhibiting paired firing. The latencies and firing patterns of the third population combined the characteristics of each of the first two patterns. It is suggested that these characteristics of unit discharges stem from the existence of two pathways from neck muscle afferents to the superior colliculus. The projection is predominantly bilateral. Units responding to neck muscle afferent stimulation are distributed throughout the superior colliculus on the basis of their latencies. Long-latency responses predominate in the superficial layers of the superior colliculus and short-latency responses, while more common in the intermediate and deep layers, predominate in the tegmentum. Extraocular muscle afferent projections to the superior colliculus constitute the single richest projection found in these experiments. While the response patterns and latencies are similar to those of the neck muscle afferents, long-latency responses are the most common and dominate in all collicular regions. Few units in the tegmentum could be excited by extraocular muscle afferents. Both extraocular muscle and neck muscle afferents show considerable convergence with one another and with retinal afferents within the superior colliculus. Cells of origin of the tectospinal tract were identified within the superior colliculus and tegmentum by antidromic excitation from the upper cervical cord. These cells were distributed predominantly within the intermediate and deep layers of the superior colliculus, and sparsely in the superficial layers and tegmentum. Almost 50% of the cells of origin of the tectospinal tract receive a convergent input from extraocular muscle and neck muscle afferents and from the retina. About 30% of the cells were inexcitable to the stimuli employed in these experiments. The significance of these projections is discussed with respect to superior collicular function in the cat and i     

Collateral branches of cerebellopontine axons reach the thalamus, superior colliculus, or inferior olive: a double-fluorescence and combined fluorescence-horseradish peroxidase study in the rat

Retrograde double-labeling methods that used two different fluorescent dyes or a fluorescent dye in combination with wheat germ agglutinin horseradish peroxidase were used in the rat to study the collateralization of cerebellopontine fibers to the thalamus, the superior colliculus, or the inferior olive. In cases with combined basilar pontine nuclei and thalamus injections, double-labeled neurons were located in the rostral part of the lateral cerebellar nucleus as well as within the interpositus anterior and interpositus posterior nuclei. These cells are medium to large in size and multipolar-shaped. A much smaller number of double-labeled cells was observed in the combined basilar pontine nuclei and superior colliculus injections. In these cases most of the double-labeled cells were intermediate- to large-sized and either bipolar- or multipolar-shaped. Such neurons were distributed throughout the rostrocaudal extent of the lateral cerebellar nucleus, with only a few double-labeled cells located in the interpositus anterior and posterior nuclei. Finally, in the cases with combined basilar pontine nuclei and inferior olive injections, double-labeled cells were located in interpositus anterior and posterior nuclei and the medial portion of the lateral cerebellar nucleus. The double-labeled cells were relatively small in size and most were spindle-shaped. No double-labeled cells were observed in the medial cerebellar nucleus in any of the three injection combinations. Based upon the observation of double-labeled neurons in the deep cerebellar nuclei in each of the three injection combinations involving the basilar pontine nuclei, we conclude that cerebellar projections to the basilar pons arise in part as collaterals of axons that project to the thalamus, superior colliculus, or the inferior olive.     

Afferent and efferent connections of the ventrolateral tegmental area in the rat

 The present study examined the organization of afferent and efferent connections of the rat ventrolateral tegmental area (VLTg) by employing the retrograde and anterograde axonal transport of Fluorogold and Phaseolus vulgaris-leucoagglutinin, respectively. Our interest was focused on whether the anatomical connections of the VLTg would provide evidence as to the involvement of this reticular area in audiomotor behavior. Our retrograde experiments revealed that minor inputs to the VLTg arise in various telencephalic structures, including the cerebral cortex. Stronger projections originate in the lateral preoptic area, the zona incerta, the nucleus of the posterior commissure and some other thalamic areas, the lateral substantia nigra, the deep layers of the superior colliculus, the dorsal and lateral central gray, the deep mesencephalic nucleus, the paralemniscal zone, the intercollicular nucleus, the external cortex of the inferior colliculus, the oral and caudal pontine reticular nucleus, the deep cerebellar nuclei, the gigantocellular and lateral paragigantocellular reticular nuclei, the prepositus hypoglossal nucleus, the spinal trigeminal nuclei, and the intermediate layers of the spinal cord. Most importantly, we disclosed strong auditory afferents arising in the dorsal and ventral cochlear nuclei and in the cochlear root nucleus. The efferent projections of the VLTg were found to be less widespread. Telencephalic structures do not receive any input from the VLTg. Moderate projections were seen to diencephalic reticular areas, the zona incerta, the nucleus of the posterior commissure, and to various other thalamic areas. The major VLTg projections terminate in the deep layers of the superior colliculus, the deep mesencephalic nucleus, the intercollicular nucleus and external cortex of the inferior colliculus, the oral and caudal pontine reticular nucleus, the gigantocellular and lateral paragigantocellular reticular nuclei, and in the medial column of the facial nucleus. From our data, we conclude that the VLTg might play a role in sensorimotor behavior. Accepted: 3 April 1997