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     

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.     

Long collateral branches of substantia nigra pars reticulata axons to thalamus,superior colliculus and reticular formation in monkey and cat. Multiple retrograde neuronal labeling with fluorescent dyes

In order to gain some impressions about the degree to which individual neurons of the pars reticulata of the substantia nigra send long collateral branches to more than one of its three major targets (thalamus, superior colliculus, reticular formation), two, or all three targets were injected with fluorescent dyes (Evan's blue, granular blue, nuclear yellow, propidium iodide) in six squirrel monkeys and four cats. The best results were obtained in the monkey brain with injections of Evan's blue in the thalamus, granular blue in the colliculus and nuclear yellow in the reticular formation. Whereas nigrothalamic and nigroreticular neurons are numerous and widely scattered throughout all parts of the pars reticulata, cells projecting only to the superior colliculus are fewer in number and restricted to a rostral-lateral zone. These results are consistent with earlier data obtained with the horseradish peroxidase method.² Although double-labeled cells with projections to both the thalamus and reticular formation occur throughout the pars reticulata, such cells are somewhat more abundant at caudal levels of the nucleus. Cells containing dyes from both the superior colliculus and reticular formation are less common and restricted to the lateral part of the pars reticulata. A small number of cells near the rostral pole of the pars reticulata contain dye from both the tectal and thalamic injection. Typically, less than two dozen cells in any case can be confidently identified as containing all three dyes and these cells are located in the rostrolateral half of the pars reticulata. Fewer than 20% of the labeled nigral cells contain more than one dye.In the cat, thalamic injection of granular blue and tectal injection of nuclear yellow indicate that most nigrotectal cells are located in the middle of the mediolateral expanse of the pars reticulata in its rostral half. Nigrothalamic cells flank the nigrotectal group medially, laterally and caudally. Where these groups border one another, several cells contain both dyes indicating that they project to both the thalamus and colliculus. In both the cats and monkeys, a less extensive cell-labeling occurs in the contralateral nigra with a pattern similar to that in the ipsilateral substantia nigra.The results indicate that several neurons of the substantia nigra's pars reticulata send long collateral branches to two or even all three of the major targets. Many reticulata cells, however, appear to project either to the thalamus, or to the superior colliculus or to the reticular formation.     

Early establishment of adult-like nigrotectal architecture in the neonatal cat: a double-labeling study using carbocyanine dyes

Virtually nothing is known about the ontogeny of substantia nigra, pars reticulata projections to the midbrain superior colliculus, even though this pathway is critical for the basal ganglia modulation of midbrain-mediated visuomotor behaviors. The present studies used the lipophilic carbocyanine dyes 1,1'-dioctodecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate and 1,1'-dioctodecyl-3,3,3',3'-tetramethylindodi, 4-chlorobenzenesulfonate salt to examine the crossed and uncrossed nigrotectal projections in neonatal cats, from parturition to 14 days postnatal (the technical limits of the tracing technique). In retrograde experiments, paired placement of the dyes in each superior colliculus produced numerous retrogradely-labeled nigrotectal neurons, with the uncrossed neurons far out numbering their crossed counterparts. No double-labeled neurons were observed, indicating that crossed and uncrossed nigrotectal neurons are segregated at birth. In anterograde experiments, dye placements into each substantia nigra, pars reticulata resulted in an iterative series of labeled patches, aligned medial-to-lateral across the intermediate and deep superior colliculus, a pattern reminiscent of the adult. Uncrossed neonatal axons had simple linear morphologies with few branch points; by contrast, crossed axons displayed more extensive terminal arbors that were distributed diffusely throughout the rostrocaudal extent of the contralateral superior colliculus In the final series of experiments, one dye was placed unilaterally in the substantia nigra, pars reticulata, while the second dye was positioned in the predorsal bundle, in order to bilaterally label superior colliculus output neurons. Although both crossed and uncrossed axons appeared to have contacted superior colliculus output neurons, crossed axons preferentially targeted the soma and proximal dendrites, whereas uncrossed terminals were distributed more distally. Throughout this early postnatal period, no significant changes in cellular morphologies or gross modification of terminal projection patterns were observed; however, the presence of growth cones in even the oldest animals studied suggests that the refinement of the nigrotectal projections extends well into postnatal life. Nevertheless, the segregation of crossed and uncrossed nigrotectal neurons into a highly organized afferent mosaic that has established synaptic contacts with superior colliculus output neurons indicates that many of the salient features characterizing nigrotectal projections are established prior to the onset of visual experience.     

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.     

Localization of nigrostriatal, nigrothalamic and nigrotectal neurons in ventricular coordinates in macaques

The topography of the substantia nigra and its subdivisions was first analysed in macaques by using a topographic technique based on ventricular landmarks. This study shows the stability of the contours of the substantia nigra and its subdivisions in various species of macaques. The anteroposterior sequence of four subdivisions was standardized by defining eight verticotransverse levels, regularly interspaced and systemically used for each experimental case. Neurons of the substantia nigra sending axons to the striatum, thalamus and superior colliculus were identified by the technique of retrograde transport of horseradish peroxidase. The nigrostriatal labeled neurons were essentially located in the ipsilateral pars compacta but also scattered dorsally in the pars mixta and ventrally in the pars reticulata. In addition, the existence of a crossed nigrostriatal pathway was demonstrated in monkeys. Nigrothalamic labeled neurons were found in the whole pars reticulata at rostral levels and only in the medial part at more caudal levels. Comparatively, nigrotectal labeled neurons were also found in the whole pars reticulata at rostral levels, but caudally, they were confined to the lateral part of the pars reticulata and the pars lateralis. It thus appears that these three nigral components may overlap at some levels of the substantia nigra. This is discussed in relation to the existence of branched axons already documented. However, the present results underline the strong tendency of the nigrotectal neurons to be segregated from the nigrothalamic ones and to be laterally located in monkeys. In addition, two nigrotectal components have been identified on the basis of their topography and their somata size: one with large somata located in the pars lateralis, probably specific to primates, and the other with smaller somata located in the pars reticulata. These two components may indicate the existence of two different functional systems.     

The striatonigral projection and nigrotectal neurons in the rat. A correlated light and electron microscopic study demonstrating a monosynaptic striatal input to identified nigrotectal neurons using a combined degeneration and horseradish peroxidase procedure

In a light and electron microscopic study of the substantia nigra of the rat, the distribution and morphology of nigrotectal neurons and the pattern of termination of striatonigral fibres have been examined following the placement of horseradish peroxidase injections in the superior colliculus and kainic acid lesions in the dorsal striatum. In confirmation of previous findings, nigrotectal neurons which had been identified by the retrograde transport of horseradish peroxidase from the superior colliculus had mainly medium sized somata, varied from fusiform to stellate in shape and were found in mainly ventral regions of the rostral two-thirds of the substantia nigra pars reticulata. On electron microscopic examination, single and multiple (from two to six) degenerating striatonigral boutons were found in synaptic contact with the soma, proximal mainstem dendrites and small dendrites (but mainly on small dendrites) of labelled nigrotectal and unlabelled nigral neurons in the ventral region of the pars reticulata. In addition, a small number of degenerating striatonigral boutons formed axoaxonic synapses with degenerating or normal boutons which were presynaptic to nigral dendrites. Almost all of the identified striatonigral synapses were of the symmetrical type, although a few degenerating boutons established asymmetrical synaptic contacts on unlabelled dendrites. These findings provide evidence of a monosynaptic input from the dorsal striatum to nigrotectal projection neurons in the substantia nigra and thus demonstrate the existence of a bineuronal pathway from the striatum through the substantia nigra to the superior colliculus. The possible significance of the pattern of termination of striatonigral fibres in the substantia nigra is discussed with reference to the known dendritic arborization of nigral neurons.     

The neurons of the substantia nigra and zona incerta which project to the cat superior colliculus are GABA immunoreactive: a double-label study using GABA immunocytochemistry and lectin retrograde transport

The neurotransmitter cytochemistry of neurons in the substantia nigra and zona incerta which project to the cat superior colliculus was examined. Neurons in both structures were double-labeled with an antibody to the transmitter GABA and a retrograde tracer, [3H]n-acetylated wheat germ agglutinin, injected into the superior colliculus. All cells in the zona incerta and substantia nigra which projected to the superior colliculus were labeled by the GABA antiserum. Most other neurons within the zona incerta and virtually all within the substantia nigra pars reticulata and pars lateralis were also labeled by the GABA antibody. By contrast, neurons in the substantia nigra pars compacta were not labeled by either the GABA antibody or wheat germ agglutinin. Nigrotectal cells in the substantia nigra were of medium to large size and most had stellate-shaped cell bodies. Zona incerta cells projecting to the superior colliculus were also of medium to large size, but most had horizontal fusiform cell bodies. This study demonstrates two new findings: (1) that all nigrotectal neurons in cat are immunoreactive to a GABA antibody and probably contain the neurotransmitter GABA; and (2) that these GABA immunoreactive neurons in cat are found not only in the substantia nigra pars reticulata but also within the pars lateralis. Zona incerta cells projecting to the superior colliculus have a different morphology but are also apparently GABAergic. These data provide an anatomical substrate for the known inhibitory action of the nigrotectal pathway on superior colliculus neurons.     

The sources of the nigrotectal pathway

The nigrotectal pathway plays a role in the generation of saccade related responses by cells in the deep layers of the superior colliculus. By using a retrograde horseradish peroxidase technique that homogeneously fills neurons, the present experiments demonstrate that the source of the nigrotectal projection to the intermediate gray layer of the grey squirrel (Sciurus carolinensis) is a heterogeneous population of neurons whose somas and dendrites are concentrated in the rostral pole of pars reticulata. This region of pars reticulata receives projections from the posterior caudate, which in turn is a target of both the pulvinar and visual cortex. In addition, these experiments reveal the presence of a second, distinct set of neurons projecting to the midbrain tectum that are located in pars lateralis of the substantia nigra. These neurons can be distinguished from those in pars reticulata by their homogeneity and by their prominent basal dendrites. Furthermore, pars lateralis of the squirrel substantia nigra is, on cytoarchitectonic and immunocytochemical grounds, a distinct subdivision that does not receive projections from the posterior caudate. We conclude that both pars reticulata and lateralis are sources of the nigrotectal pathway. In addition, our results suggest, on connectional grounds, that the rostral pole of pars reticulata may be specialized to subserve the visual guidance of orienting movements.     

Projections from the superior colliculus to a region of the central mesencephalic reticular formation (cMRF) associated with horizontal saccadic eye movements

Summary Radioactive wheatgerm agglutinin (WGA) and horseradish peroxidase (HRP) were injected into portions of the mesencephalic reticular formation at sites where electrical stimulation induced either small or large contralateral horizontal saccadic eye movements. We have designated this region as the Central MRF (cMRF). It contains both cells and fiber tracts, including the efferent output of the superior colliculus (SC), destined for the dorsal tegmental decussation and the predorsal bundle. Cells labelled by WGA and HRP injections were found in the intermediate and deep layers of the superior colliculus and the adjacent central gray matter on the ipsilateral side. Injections into the dorsal cMRF, at sites where small saccades were induced, caused labelling of cells in the rostral intermediate layer of SC. Injections into the ventral cMRF, at points where large saccades were elicited, caused labelling of cells in the caudal intermediate layer of SC. The deepest layers of SC and the adjacent central gray were also labelled from the small eye movement region of dorsal cMRF. We interpret these findings to indicate that the intermediate layers of SC send axonal projections to the horizontal eye movement region of the MRF in a topographic fashion. The projection from the intermediate layer is organized so that regions in SC and cMRF related to small or to large eye movements are interconnected. The results support the hypothesis that cMRF is a topographically organized area, involved, like SC, in the control of eye movements. Since both cMRF and the superior colliculus project to areas of the pons and medulla where saccadic eye movements are produced, they could give rise to parallel pathways for the generation of contralateral saccades.Abbreviations III oculomotor nucleus - IV trochlear nucleus - ap area pretectalis - BC brachium conjunctivum - BSC brachium of the superior colliculus - cg central gray - cMRF central MRF - d deep layer of SC - DAB diaminobenzidine - EOG electro-oculography - h habenula nuclei - HRP horseradish peroxidase - iC interstitial nucleus of Cajal - ic inferior colliculus - li nucleus limitans - mg medial geniculate body - MLF medial longitudinal fasciculus - nIII oculomotor nerve - nIV trochlear nerve - on olivary nucleus - p pulvinar - PC posterior commissure - riMLF rostral interstitial nucleus of the MLF - rn red nucleus, pars magnocellularis - rnp red nucleus, pars parvocellularis - s superficial layer of SC - SC superior colliculus - sl sublentiform nucleus - sn substantia nigra - TMB tetramethyl benzidine - TR tractus retroflexus - WGA wheatgerm agglutinin Supported by NIH Research grant EY 02296, Deutsche Forschungsgemeinschaft grant SFB 200/A3 and Core Center grant EY 01867     

The nigrotectal projection and tectospinal neurons in the rat. A light and electron microscopic study demonstrating a monosynaptic nigral input to identified tectospinal neurons

In order to investigate the nigro-tecto-spinal pathway in the rat, the pattern of termination of nigrotectal fibres and the distribution of tectospinal neurons have been investigated in a light and electron microscopic study of the superior colliculus. In addition, the pattern of termination of nigrotectal fibres was compared to the pattern of acetylcholinesterase staining. The light microscopic studies showed that the nigrotectal fibres, which had been identified by anterograde transport of horseradish peroxidase from the substantia nigra, terminated in a distinctive clustered pattern throughout the rostrocaudal extent of the stratum griseum intermedium, stratum album intermedium and adjacent dorsal portion of the stratum griseum profundum of the ipsilateral superior colliculus. The clusters of nigrotectal terminals formed a series of branching, interconnected longitudinal columns which largely corresponded with the pattern of acetylcholinesterase staining. The tectospinal neurons, which had been identified by retrograde transport of horseradish peroxidase from the spinal cord, had mainly large-sized somata, were stellate in shape with multiple long dendrites, and formed variable-sized clusters of 4-15 neurons within lateral regions of the ventral stratum album intermedium and dorsal stratum griseum profundum. In experiments where both the nigrotectal terminals and the tectospinal neurons were labelled by the transport of horseradish peroxidase, the clusters of tectospinal neurons largely corresponded with the regions of densest nigrotectal fibre termination in the lateral regions of the superior colliculus. In addition, a small contralateral nigrotectal projection was localized in the rostrolateral region of the superior colliculus where the crossed fibres terminated in a clustered pattern in alignment with clusters of tectospinal neurons in this region. Electron microscopic examination of the superior colliculus following ibotenic acid lesions in the substantia nigra and horseradish peroxidase injections in the spinal cord showed multiple degenerating nigrotectal boutons in synaptic contact with the soma and the mainstem and secondary dendrites of labelled tectospinal neurons in the lateral regions of the stratum album intermedium and stratum griseum profundum of the superior colliculus. The majority of the degenerating nigrotectal boutons showed electron-lucent degenerative changes and were in axodendritic contact. All of the identified nigrotectal synapses were of the symmetrical type.(ABSTRACT TRUNCATED AT 400 WORDS)     

Topographic projections from the basal ganglia to the nucleus tegmenti pedunculopontinus pars compacta of the cat with special reference to pallidal projections

Summary Projections from the basal ganglia to the nucleus tegmenti pedunculopontinus pars compacta (TPC) were studied by using anterograde and retrograde tracing techniques with horseradish peroxidase conjugated with wheat germ agglutinin (WGA-HRP) in the cat. Following WGA-HRP injections into the medial TPC area, a substantial number of retrogradely labeled cells were seen in the entopeduncular nucleus (EP) and medial half of the substantia nigra pars reticulata (SNr), whereas following WGA-HRP injections into the lateral TPC area, labeled cells were marked in the caudal half of the globus pallidus (GP) and lateral half of the SNr. To confirm the retrograde tracing study, WGA-HRP was injected into the EP or the caudal GP, and anterograde labeling was observed in the TPC areas. Terminal labeling was located in the medail TPC area in the EP injection case, while terminal labeling was observed in the lateral TPC area in the caudal GP injection case. Projections from the striatum to the pallidal complex (the EP and the caudal GP) were also studied autoradiographically by injecting amino acids into various parts of the caudate nucleus and the putamen. Terminal labeling was distributed over the whole extent of the EP and the rostral GP following injections into the rostral striatum (the head of the caudate nucleus or the rostral part of the putamen), while terminal labeling was distributed over the caudal GP following injections into the caudal striatum (the body of the caudate nucleus or the caudal part of the putamen). From these findings, we conclude that there exists a medio-lateral topography in the projection from the basal ganglia to the TPC: The EP receives afferent projections from the rostral striatum and projects to the medial TPC area, whereas the caudal GP receives projections from the caudal striatum and sends fibers to the lateral TPC area.Abbreviations BC brachium conjunctivum - CD caudate nucleus - CP cerebral peduncle - DBC decussation of the brachium conjunctivum - EP entopeduncular nucleus - GP globus pallidus - IC internal capsule - ICo inferior colliculus - LH lateral habenular nucleus - ML medial lemniscus - PN pontine nuclei - PUT putamen - SCo superior colliculus - SI substantia innominata - SN substantia nigra - SNc substantia nigra pars compacta - SNr substantia nigra pars reticulata - STN subthalamic nucleus - TH thalamus - TPC nucleus tegmenti pedunculopontinus pars compacta     

The projection from superior colliculus to cuneiform area in the rat

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)     

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.     

Functional and ultrastructural neuroanatomy of interactive intratectal/tectonigral mesencephalic opioid inhibitory links and nigrotectal GABAergic pathways: Involvement of GABAA and μ1-opioid receptors in the modulation of panic-like reactions elicited by electrical stimulation of the dorsal midbrain

In the present study, the functional neuroanatomy of nigrotectal–tectonigral pathways as well as the effects of central administration of opioid antagonists on aversive stimuli-induced responses elicited by electrical stimulation of the midbrain tectum were determined. Central microinjections of naloxonazine, a selective μ₁-opiod receptor antagonist, in the mesencephalic tectum (MT) caused a significant increase in the escape thresholds elicited by local electrical stimulation. Furthermore, either naltrexone or naloxonazine microinjected in the substantia nigra, pars reticulata (SNpr), caused a significant increase in the defensive thresholds elicited by electrical stimulation of the continuum comprised by dorsolateral aspects of the periaqueductal gray matter (dlPAG) and deep layers of the superior colliculus (dlSC), as compared with controls. These findings suggest an opioid modulation of GABAergic inhibitory inputs controlling the defensive behavior elicited by MT stimulation, in cranial aspects. In fact, iontophoretic microinjections of the neurotracer biodextran into the SNpr, a mesencephalic structure rich in GABA-containing neurons, show outputs to neural substrate of the dlSC/dlPAG involved with the generation and organization of fear- and panic-like reactions. Neurochemical lesion of the nigrotectal pathways increased the sensitivity of the MT to electrical (at alertness, freezing and escape thresholds) and chemical (blockade of GABA_A receptors) stimulation, suggesting a tonic modulatory effect of the nigrotectal GABAergic outputs on the neural networks of the MT involved with the organization of the defensive behavior and panic-like reactions. Labeled neurons of the midbrain tectum send inputs with varicosities to ipsi and contralateral dlSC/dlPAG and ipsilateral substantia nigra, pars reticulata and compacta, in which the anterograde and retrograde tracing from a single injection indicates that the substantia nigra has reciprocal connections with the dlSC/dlPAG featuring close axo-somatic and axo-dendritic appositions in both locations. In addition, ultrastructural approaches show inhibitory axo-axonic synapses in MT and inhibitory axo-somatic/axo-axonic synapses in the SNpr. These findings, in addition to the psychopharmacological evidence for the interaction between opioid and GABAergic mechanisms in the cranial aspects of the MT as well as in the mesencephalic tegmentum, offer a neuroanatomical basis of a pre-synaptic opioid inhibition of GABAergic nigrotectal neurons modulating fear in defensive behavior-related structures of the cranial mesencephalon, in a short link, and through a major neural circuit, also in GABA-containing perikarya and axons of nigrotectal neurons.     

Corticonigral projections from area 6 in the raccoon

Summary The corticonigral projections from area 6 in the raccoon were investigated using the autoradiographic tracing method. Injections of tritiated proline and leucine were made into either medial or lateral area 6 subdivisions. Uniformly distributed silver grains were observed overlying the ipsilateral substantia nigra pars compacta (SNc) while more restricted foci of label indicative of fiber labeling were present in the substantia nigra pars reticulata (SNr). Autoradiographic label was also present in the substantia nigra pars lateralis (SNl), the retrorubral area and the ventral tegmental area of Tsai. The existence of corticonigral projections from area 6 may serve to modulate SNc activity as a whole and provide an important substrate for the cerebral control of movement.Abbreviations cp cerebral peduncle - IP interpeduncular nucleus - PG pontine gray - R red nucleus - RR retrorubral area - SNc substantia nigra, pars compacta - SNl substantia nigra, pars lateralis - SNr substantia nigra, pars reticularis - VTA ventral tegmental area     

Functional and ultrastructural neuroanatomy of interactive intratectal/tectonigral mesencephalic opioid inhibitory links and nigrotectal GABAergic pathways: involvement of GABAA and mu1-opioid receptors in the modulation of panic-like reactions elicited by electrical stimulation of the dorsal midbrain

In the present study, the functional neuroanatomy of nigrotectal–tectonigral pathways as well as the effects of central administration of opioid antagonists on aversive stimuli-induced responses elicited by electrical stimulation of the midbrain tectum were determined. Central microinjections of naloxonazine, a selective μ₁-opiod receptor antagonist, in the mesencephalic tectum (MT) caused a significant increase in the escape thresholds elicited by local electrical stimulation. Furthermore, either naltrexone or naloxonazine microinjected in the substantia nigra, pars reticulata (SNpr), caused a significant increase in the defensive thresholds elicited by electrical stimulation of the continuum comprised by dorsolateral aspects of the periaqueductal gray matter (dlPAG) and deep layers of the superior colliculus (dlSC), as compared with controls. These findings suggest an opioid modulation of GABAergic inhibitory inputs controlling the defensive behavior elicited by MT stimulation, in cranial aspects. In fact, iontophoretic microinjections of the neurotracer biodextran into the SNpr, a mesencephalic structure rich in GABA-containing neurons, show outputs to neural substrate of the dlSC/dlPAG involved with the generation and organization of fear- and panic-like reactions. Neurochemical lesion of the nigrotectal pathways increased the sensitivity of the MT to electrical (at alertness, freezing and escape thresholds) and chemical (blockade of GABA_A receptors) stimulation, suggesting a tonic modulatory effect of the nigrotectal GABAergic outputs on the neural networks of the MT involved with the organization of the defensive behavior and panic-like reactions. Labeled neurons of the midbrain tectum send inputs with varicosities to ipsi and contralateral dlSC/dlPAG and ipsilateral substantia nigra, pars reticulata and compacta, in which the anterograde and retrograde tracing from a single injection indicates that the substantia nigra has reciprocal connections with the dlSC/dlPAG featuring close axo-somatic and axo-dendritic appositions in both locations. In addition, ultrastructural approaches show inhibitory axo-axonic synapses in MT and inhibitory axo-somatic/axo-axonic synapses in the SNpr. These findings, in addition to the psychopharmacological evidence for the interaction between opioid and GABAergic mechanisms in the cranial aspects of the MT as well as in the mesencephalic tegmentum, offer a neuroanatomical basis of a pre-synaptic opioid inhibition of GABAergic nigrotectal neurons modulating fear in defensive behavior-related structures of the cranial mesencephalon, in a short link, and through a major neural circuit, also in GABA-containing perikarya and axons of nigrotectal neurons.     

Laminar organization of the substantia nigra pars reticulata in the cat

Using a semihorizontal section plane tangential to the ventral surface of the cerebral peduncle, the authors re-examined cyto-, myelo- and dendroarchitecture, acetylcholinesterase activity, afferent fibers, and efferent projection neurons of the substantia nigra pars reticulata. In the semihorizontal section plane, the substantia nigra pars reticulata was a disc-shaped nucleus and contained two to three myelinated fiber bundles running from anteromedial to posterolateral. Bands of high acetylcholinesterase activity existed parallel to the anteromedial-posterolateral direction. The Golgi silver impregnation study revealed that many nigral neurons extended their varicose dendrites anteromedially and posterolaterally. In cases with injections of wheat germ agglutinated horseradish peroxidase into the neostriatum or injections of tritiated leucine into the subthalamic nucleus, anterogradely labeled afferent fibers and axon terminals in the substantia nigra pars reticulata were organized into bands in the same anteromedial-posterolateral direction. In cases with injections of wheat germ agglutinated horseradish peroxidase into either the superior colliculus, the pedunculopontine tegmental nucleus or the ventromedial nucleus of the thalamus, retrogradely labeled neurons were also clustered along the anteromedial-posterolateral direction with their dendrites extending anteromedially and posterolaterally. The present findings strongly suggest that the substantia nigra pars reticulata has a laminar organization.     

A direct projection from superior colliculus to substantia nigra pars compacta in the cat

Dopaminergic neurons exhibit a short-latency, phasic response to unexpected, biologically salient stimuli. The midbrain superior colliculus also is sensitive to such stimuli, exhibits sensory responses with latencies reliably less than those of dopaminergic neurons, and, in rat, has been shown to send direct projections to regions of the substantia nigra and ventral tegmental area containing dopaminergic neurons (e.g. pars compacta). Recent electrophysiological and electrochemical evidence also suggests that tectonigral connections may be critical for relaying short-latency (<100 ms) visual information to midbrain dopaminergic neurons. By investigating the tectonigral projection in the cat, the present study sought to establish whether this pathway is a specialization of the rodent, or whether it may be a more general feature of mammalian neuroanatomy. Anterogradely and retrogradely transported anatomical tracers were injected into the superior colliculus and substantia nigra pars compacta, respectively, of adult cats. In the anterograde experiments, abundant fibers and terminals labeled with either biotinylated dextran amine or Phaseolus vulgaris leucoagglutinin were seen in close association with tyrosine hydroxylase-positive (dopaminergic) somata and processes in substantia nigra pars compacta and the ventral tegmental area. In the retrograde experiments, injections of biotinylated dextran amine into substantia nigra produced significant retrograde labeling of tectonigral neurons of origin in the intermediate and deep layers of the ipsilateral superior colliculus. Approximately half of these biotinylated dextran amine-labeled neurons were, in each case, shown to be immunopositive for the calcium binding proteins, parvalbumin or calbindin. Significantly, virtually no retrogradely labeled neurons were found either in the superficial layers of the superior colliculus or among the large tecto-reticulospinal output neurons. Taken in conjunction with recent data in the rat, the results of this study suggest that the tectonigral projection may be a common feature of mammalian midbrain architecture. As such, it may represent an additional route by which short-latency sensory information can influence basal ganglia function.