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.     

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

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

Projections from the intracerebellar nuclei to the ventral midbrain tegmentum in the rat

The present study was undertaken to provide anatomical evidence, in the rat, for a direct projection from the cerebellum towards structures, other than the red nucleus, which belong to the ventral midbrain tegmentum, by using the retrograde as well as the anterograde horseradish peroxidase transport method. Following unilateral injection in the ventral midbrain tegmentum of horseradish peroxidase, free or conjugated to wheat germ agglutinin, sparing the red nucleus, retrogradely labeled neurons were found in the contralateral cerebellar lateral nucleus and, at lower density, in the interpositus nucleus. No labeled neurons were found in the fastigial nucleus of either side. Anterogradely labeled axons from lectin coupled horseradish peroxidase injection sites in the lateral and interpositus nuclei reached the contralateral ventral midbrain tegmentum. Terminal labeling was observed in the entire red nucleus as well as in the lateral division of the ventral tegmental area of Tsai, in the dorsal region of the substantia nigra pars compacta, and in the medial part of the retrorubral field. No terminal labeling was found in the caudal linear nucleus, interfascicular nucleus, peripeduncular nucleus, rostral linear nucleus of the raphe, substantia nigra pars lateralis and the substantia nigra pars reticulata. Terminal labeling was also not observed in the ventral midbrain tegmentum following horseradish peroxidase injection in lateral and interpositus nuclei of rats pretreated with kainic acid. In conclusion, it is noteworthy that, besides the red nucleus, the sole structures of ventral midbrain tegmentum receiving cerebellar efferents are those with a higher density of dopaminergic cells.     

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     

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.     

Synaptic organization of GABAergic inputs from the striatum and the globus pallidus onto neurons in the substantia nigra and retrorubral field which project to the medullary reticular formation.

Anatomical tract-tracing and immunohistochemical techniques involving correlated light and electron microscopy were used to determine whether the descending striatal and pallidal afferents to the substantia nigra pars reticulata converge onto individual neurons projecting to the pontomedullary and medullary reticular formation in the rat. Injections of biocytin into the ventrolateral region of the striatum and Phaseolus vulgaris-leucoagglutinin into the ventrolateral and caudal regions of the globus pallidus led to overlapping anterogradely labelled terminal fields within the dorsolateral substantia nigra pars reticulata. These terminal fields were punctuated by neurons which had been retrogradely labelled following injections of wheatgerm agglutinin conjugated to horseradish peroxidase into the lateral pontomedullary reticular formation. The anterogradely labelled striatal and pallidal terminals displayed different morphological characteristics; the striatal terminals were small and diffusely distributed throughout the neuropil without any particular neuronal association whereas the pallidal terminals were large and formed pericellular baskets around the perikarya of retrogradely and non-retrogradely labelled nigral neurons. In areas of the substantia nigra where there was an overlap between the two terminal fields, individual retrogradely labelled nigroreticular neurons were found to be apposed by both sets of anterogradely labelled terminals. Electron microscopic analysis revealed that the striatonigral and pallidonigral terminals displayed different ultrastructural features, the striatal terminals were small, contained few mitochondria and formed symmetric synaptic contacts predominantly with the distal dendrites of nigroreticular neurons whereas the pallidal terminals were large, contained numerous mitochondria and formed symmetric synaptic contacts preferentially with perikarya and proximal dendrites of nigroreticular neurons. Post-embedding immunohistochemical staining revealed that both striatonigral and pallidonigral terminals, some which formed synaptic contact with nigroreticular neurons, displayed GABA immunoreactivity. Examination of twelve retrogradely labelled neurons in the electron microscope revealed that all received synaptic inputs from both sets of anterogradely labelled terminals. In addition to the substantia nigra pars reticulata, neurons of the retrorubral field were also retrogradely labelled following injections of wheatgerm agglutinin conjugated to horseradish peroxidase into pontomedullary reticular formation. These retrorubroreticular neurons were part of a continuum of labelled cells which extended from the dorsolateral substantia nigra pars reticulata caudally into the retrorubral field. When combined with anterograde tracing methods it was found that the retrorubroreticular neurons received synaptic inputs from pallidal terminals which were morphologically similar to the pallidonigral terminals and formed symmetric synapses with the neuronal somata and proximal dendrites. In contrast to nigroreticular neurons, the stratonigral terminals were not seen in contact with retrorubroreticular cells.(ABSTRACT TRUNCATED AT 400 WORDS)     

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     

Ascending projections of presumed dopamine-containing neurons in the ventral tegmentum of the rat as demonstrated by horseradish peroxidase

The projections of presumed dopamine-containing neurons in the zona compacta of the substantia nigra and the ventral tegmental area were examined by stereotaxic injections of horseradish peroxidase into diverse cortical and subcortical regions which are known to include dopamine-containing terminals. Neurons in the lateral half of the substantia nigra pars compacta were labelled after injections into the caudolateral aspect of the caudate-putamen, while neurons in the medial part of the substantia nigra pars compacta and lateral aspect of the ventral tegmental area projected to the anteromedial portion of the caudate putamen. Injections of horseradish peroxidase into the amygdala resulted in the appearance of reactive neurons in the anterior portion of the ventral tegmental area, but the more caudally located entorhinal cortex received projections from the posterior half of the ventral tegmental area. Injections of horseradish peroxidase into the frontal cortex, anterior to the genu, produced scattered labelled cells in the rostral half of the ventral tegmental area, whereas more posterior injections into the cingulate cortex resulted in the appearance of reactive cells which were confined to the medial one-quarter of the substantia nigra pars compacta. The near-midline structure, the lateral septum, was innervated by neurons with cell bodies primarily in the medial half of the ventral tegmental area. Injections of horseradish peroxidase into the nucleus accumbens, which contains very high levels of dopamine, resulted in the appearance of many labelled neurons throughout the ventral tegmental area and some reactive neurons in the medial part of the substantia nigra pars compacta. A few labelled cells were also occasionally observed in the contralateral ventral tegmental area after accumbens injections.These results suggest that although there is considerable overlap, and that the same subdivisions within the substantia nigra pars compacta and the ventral tegmental area appear to innervate diverse regions of the forebrain, there also exists a general topographical organization with respect to the projections of these neurons.Injections of horseradish peroxidase into some of the forebrain regions also resulted in the appearance of reactive cells in mesencephalic nuclei not known to contain dopaminergic perikarya. For example, labelled cells were observed in the supramamillary nucleus after injections into the frontal cortex, entorhinal cortex, accumbens and lateral septum. Injections into the amygdala produced reactive cells in the suprageniculate nucleus, the peripeduncular nucleus, and the magnocellular nucleus of the medial geniculate. These latter results are discussed with reference to the possibility that such pathways may mediate the responsiveness of cells in the amygdala to a wide range of sensory stimuli.     

大鼠纹状体边缘区的传入投射—WGA-HRP逆行和顺行追踪研究

用WGA-HRP顺行和逆行追踪法研究了大鼠纹状体边缘区的传入投射。当WGA-HRP微电泳入纹状体边缘区时,逆行标记胞体见于黑质外侧部及背外侧区,包括脚周核、丘脑后板内核等;当WGA-HRP庄射于黑质外侧部及背外侧区时,纹状体边缘区中可见顺行标记纤维从腹侧向背侧走行,并可见许多终末终止于此。结果表明,黑质外侧部及背外侧区,包括脚周核及丘脑后板内核等投射到大鼠纹状体边缘区,可能和听觉、运动及边缘系统等功能有关。     

Collateral projection from the substantia nigra to the striatum and superior colliculus in the rat

Our retrograde fluorescent double labeling study demonstrated the existence of divergent collateral projections from the substantia nigra to the striatum and superior colliculus in the rat. These bifurcating projection neurons were located predominantly in the ventrolateral portions of the substantia nigra pars reticulata at its rostral level, where they formed a narrow band along the boundary between the substantia nigra and cerebral peduncle. Such specific projection cells were also seen in the substantia nigra pars lateralis. However, nigral neurons did not give off axonal branches to the striatum and ventromedial thalamic nucleus. The new nigral cell population proposed here might constitute a neuroanatomical substrate for abnormal saccadic eye movements clinically manifested by many parkinsonian patients.     

Different neuronal location of [3H]SCH 23390 binding sites in pars reticulata and pars compacta of the substantia nigra in the rat

The precise neuronal localization of D1 receptors in the substantia nigra has been studied autoradiographically in the rat by measuring the alterations of [3H]SCH 23390 binding site densities in this brain area after 6-hydroxydopamine (6-OHDA) induced destruction of nigrostriatal dopaminergic neurons and after ibotenate-induced lesion of striatal afferents. 6-OHDA-induced nigral lesion provoked a total loss of [3H]SCH 23390 binding sites in the pars compacta and pars lateralis (but not in the pars reticulata) of the substantia nigra. In contrast, ibotenate-induced striatal lesion caused a large diminution of the [3H]ligand binding site density in the pars reticulata but not in the pars compacta and pars lateralis of the substantia nigra. These results suggest that D1 receptors in the pars compacta or pars lateralis of the substantia nigra are located on the dopaminergic perikarya whereas those D1 receptors present in the pars reticulata of the substantia nigra lie on the terminals of nigral afferents of striatal origin.     

Nigral dopamine autoreceptors are exclusively of the D2 type: quantitative autoradiography of [125I]iodosulpride and [125I]SCH 23982 in adjacent brain sections

The effect of unilateral 6-hydroxydopamine lesions of the medial forebrain bundle on the specific binding of [125I]iodosulpride and [125I]SCH 23982 in the rat substantia nigra was determined by quantitative autoradiography of adjacent sections. The specific binding of [125I]iodosulpride was reduced by 40-70% on the lesioned side in the substantia nigra pars compacta, reticulata, lateralis and in the ventral tegmental area. In contrast, the specific [125I]SCH 23982 binding was unchanged in all subdivisions of the substantia nigra. The results indicate that dopamine autoreceptors are present in the substantia nigra and in the ventral tegmental area and that they are exclusively of the D2 type.     

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.     

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.     

A lectin horseradish peroxidase study of the origin of ascending fibers in the medial forebrain bundle of the rat. The upper brainstem

The origins of projections within the medial forebrain bundle from the upper brainstem were examined with the horseradish peroxidase technique. Labeled cells were found in approximately 15 upper brainstem nuclei following injections of a conjugate of horseradish peroxidase and wheat germ agglutinin at various levels of the medial forebrain bundle. Labeled nuclei included (from caudal to rostral): dorsal and ventral parabrachial nuclei; Kolliker-Fuse nucleus; dorsolateral tegmental nucleus; A7 (lateral pontine tegmentum medial to lateral lemniscus); median and dorsal raphe nuclei; distinct group of cells oriented mediolaterally in the dorsal pontine tegmentum below the central gray; B9 (ventral midbrain tegmentum dorsal to medial lemniscus); retrorubral nucleus; nucleus of Darkschewitsch, interfascicular nucleus; rostral and caudal linear nuclei; ventral tegmental area; medial part of substantia nigra, pars compacta; and the supramammillary nucleus. With the exception of the ventral parabrachial nucleus, Kolliker-Fuse, A7, B9 and substantia nigra, pars compacta, each of the nuclei mentioned above sent strong projections along the medial forebrain bundle to the rostral forebrain. Sparse labeling was observed throughout the pontine and midbrain reticular formation. With the exception of the dorsal raphe nucleus, projections to the most anterior regions of the medial forebrain bundle (level of the anterior commissure) essentially only arose from presumed dopamine-containing nuclei-retrorubral nucleus (A8 area), interfascicular nucleus, rostral and caudal linear nuclei, substantia nigra pars compacta, and ventral tegmental area. Evidence was reviewed indicating that major forebrain sites of termination for these dopaminergic nuclei are structures that have been collectively referred to as the 'ventral striatum'. It is concluded from the present findings that several pontine and mesencephalic cell groups are in a position to exert a strong, direct effect on structures in the anterior forebrain and that the medial forebrain bundle is the main communication route between the upper brainstem and the forebrain.     

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.     

Origin,course and termination of dopaminergic substantia nigra neurons projecting to the amygdaloid complex in the cat

The organization of dopaminergic neurons projecting to the amygdala was examined using retrograde (horseradish peroxidase histochemistry) and anterograde ([³H]leucine autoradiography) transport methods and Falck-Hillarp histofluorescence techniques combined with microspectrofluorometry and radiofrequency lesions. Cell bodies located within the pars lateralis and pars compacta of the substantia nigra were found to project to the lateral and central amygdaloid nuclei, respectively. Both of these areas within the substantia nigra contained dopaminergic perikarya, while the central and lateral amygdaloid nuclei contained fluorescent varicosities with features indicative of dopaminergic neurons. Lesions restricted to the pars lateralis of the substantia nigra resulted in a loss of fluorescence in the lateral amygdaloid nucleus. Autoradiographic experiments revealed that the projections from the pars lateralis did not run with fibers originating from the pars compacta in the nigrostriatal tract but rather had their own course occupying a lateral position adjacent to the cerebral peduncle and joining the ventral amygdalo-fugal bundle.The data indicate that, in the cat, there are two separate dopaminergic projections to the amygdala arising from the substantia nigra.     

Biochemical evidence for γ-aminobutyrate containing fibres from the nucleus accumbens to the substantia nigra and ventral tegmental area in the rat

Glutamate decarboxylase activity, a specific marker for γ-aminobutyrate-containing neurons, has been analysed in microdissected samples from rat mesencephalon following unilateral electrocoagulations of the nucleus accumbens. This lesion resulted in a consistent decrease of 50% in the enzyme activity in the rostromedial substantia nigra, and a slight, but insignificant decrease (?15%) in the medial parts of the caudal pars compacta of the substantia nigra. No change was found in the lateral pars compacta or the central pars reticulata. In the ventral tegmental area, the highest activity was found in the rostromedial part, adjacent to the mammillary body. At this level, a significant decrease of 20% was found in the ventral tegmental area on the lesioned side. In contrast, the activities in the medial accessory optic nucleus and the caudal ventral tegmental area adjacent to the interpenduncular nucleus were unchanged.The results indicate that the nucleus accumbens sends γ-aminobutyrate-containing fibres to the rostromedial substantia nigra and to the rostral ventral tegmental area. The caudal ventral tegmental area, the lateral pars compacta and the central pars reticulata do not receive measurable amounts of such fibres.     

The lamellar organization of the rat substantia nigra pars reticulata: distribution of projection neurons.

As a major output station of the basal ganglia, the pars reticulata of the substantia nigra has stimulated much interest. In the past two decades there has been a growing body of evidence for a partition of this structure into separate channels to express the striatal processing. To further our knowledge on the functional partitioning of the rodent substantia nigra pars reticulata, the regional distribution of the nigral efferent cell groups that provide innervation of thalamus, colliculus and tegmentum has been detailed in rat using the wheatgerm agglutinin conjugated with horseradish peroxidase as an axonal tracer. To ensure a total visualization of the nigral efferent neurons we have, in a preliminary study, determined the total extent of the nigral terminal field in each of the nigral target structures using the anterograde transport of wheatgerm agglutinin-horseradish peroxidase and Phaseolus vulgaris leucoagglutinin. At variance with the classical view that nigral cells innervating distinct target structures form functionally distinct subnuclei, the results suggest a nigral compartmentation that rather relies upon specific associations of efferent cell groups. As disclosed, these associations are specified by topographic rules and spatially ordered in a series of curved laminae enveloping an excentrated dorsolateral core. In this onion-like model of the substantia nigra pars reticulata, each lamella defines an associative unit composed of a set of neurons innervating particular loci of thalamus, colliculus and/or tegmentum. This lamellar partitioning bestows the ability upon the substantia nigra to dispatch the striatal outflow via parallel and divergent channels to functionally associated target areas in thalamus and brainstem.     

Cytoarchitecture of the substantia nigra in the rat

Midbrains of ten young adult rats were sectioned serially in three planes to study the detailed cytoarchitecture of the substantia nigra. These neurons measure 8 to 17 μ in diameter. In comparison, the largest neurons in the midbrain measure 20 to 40 μ; hence, neurons are designated according to size as follows: those measuring 18 to 40 μ, large; 12 to 17 μ, medium; and 8 to 11 μ, small. The substantia nigra of the rat contains non-pigmented neurons in three divisions: pars reticulata, pars compacta, and pars lateralis. The pars reticulata is the largest division and has the longest rostrocaudal extent. It contains neurons of small size medially and of medium size laterally. This finding correlates with described differences in connections. Three-dimensionally, the pars reticulata is an oblate spheroid with the long axis in the rostrocaudal plane. The pars compacta is a triangular layer dorsal to reticulata. It is subdivided into rostral and caudal portions at the level of the fibers of the basal optic root. Neurons in both subdivisions are medium in size, but cells rostrally are darker than those caudally. The pars lateralis is a column of neurons with its long axis located in the rostrocaudal plane. It lies dorsolateral to the pars reticulata and the pars compacta, with occasional connections to both by cellular strands. The pars lateralis has rostral and caudal portions; neurons rostrally are medium in size and round; caudally, however, neurons are variable in size, dark, stellate or fusiform, and have long processes.