Hendrik Jan ten Donkelaar

Early development of descending pathways from the brain stem to the spinal cord in Xenopus laevis.

SummaryThe early development of descending pathways from the brain stem to the spinal cord has been studied in Xenopus laevis tadpoles. The relatively protracted development of this permanently aquatic amphibian as well as its transparency during development make this animal particularly attractive for experimental studies. Between the 5th and 10th myotome the spinal cord was crushed with a thin needle and dry horseradish peroxidase (HRP) crystals were applied. After a survival time of one day the tadpoles were fixed and the brain and spinal cord were stained as a whole according to a modification of the heavy metal intensification of the DAB-reaction, cleared in cedarwood oil and examined as wholemounts.At stage 28 (the neural tube has just closed) the first brain stem neurons projecting to the spinal cord were found in what appear to be the nucleus reticularis inferior and medius. At this stage of development the first, uncoordinated swimming movements can be observed. At stage 30/31 (the tailbud is visible) both Mauthner cells project to the spinal cord as well as the interstitial nucleus of the fasciculus longitudinalis medialis situated in the mesencephalon. Towards stage 35/36 (the tail is now clearly visible), a more extensive reticulospinal innervation of the spinal cord appears, now including cells of the nucleus reticularis superior. At this stage also the first vestibulospinal and raphespinal projections were found. At stage 43/44 (the tadpoles have now a well-developed tail) the pattern of reticulospinal projections appears to be completed with the presence of labeled neutrons in the nucleus reticularis isthmi. From stage 43/44 on, the number of HRP-positive cells is steadily increasing. At stage 47/48, when the hindlimb buds appear, the descending projections to the spinal cord are comparable with the adult situation except for the absence of a rubrospinal and a hypothalamospinal projection.The observations demonstrate that already very early in development reticulospinal fibers and, somewhat later, Mauthner cell axons and vestibulospinal fibers innervate the spinal cord. Furthermore, a caudorostral gradient appears to exist with regard to the development of descending projections to the spinal cord. However, the interstitial nucleus of the fasciculus longitudinalis medialis forms an exception to this rule.

The Human Substantia Nigra and Ventral Tegmental Area

The present study comprises a cytoarchitectonic analysis of the human substantia nigra (SN) and ventral tegmental area (VTA); a discussion of their chemoarchitecture and fiber connections (mainly based on tract-tracing studies in primates) preceded by an overview of the wealth of tract-tracing data in rodents; a discussion of the involvement of the SN/VTA complex in Parkinsons disease (PD) and related disorders and in Alzheimers disease (AD), including some quantitative data; and finally, some functional and pathophysiological considerations, relating nigral organization to pathophysiology and hypotheses on the etiology and distribution of AD and PD. DAergic cell populations in the mesencephalon (SN pars compacta, VTA, and the retrorubral area A8) which give rise to well-developed, DAergic, mesotelencephalic pathways, including a distinct mesostriatal system, and a substance P-immunoreactive striatotegmental system which projects to the SN pars reticulata and VTA appear to be common to reptiles, birds, and mammals (Sect. 3.1). The extensive literature on the organization of the SN/VTA complex in rats is summarized in Sect. 3.2. The mesotelencephalic projection is organized along inverted dorsal to ventral, medial to lateral, and rostral to caudal topographies. A dense DAergic innervation is characteristic of the entire striatal complex, including the caudate-putamen (the dorsal striatum), the nucleus accumbens, and the olfactory tubercle (the ventral striatum). This mesostriatal projection is compartmentally organized with distinct sets of DAergic neurons projecting to striosomes and extrasriosomal matrix, respectively, suggesting specialized channels directed at DAergic modulation of sensorimotor processing in the striatal matrix and limbic related mechanisms represented in the striosomal system. The VTA and medial part of the SN give rise to the DAergic mesolimbocortical system with extensive projections to limbic, allocortical, and neocortical structures. The striatonigral output pattern in rats is organized in such a way that the dorsal striatum mainly innervates the SN pars reticulata, whereas the ventral striatum projects predominantly to the VTA and medial part of the SN. Within the striatonigral projections in rats some interesting channels can be recognized, relating the sensorimotor cortex, via its corticostriatal projections, to that region of the SN giving rise to the nigrothalamic projection, and the visual cortex to the nigrotectal component of the SN pars reticulata.(ABSTRACT TRUNCATED AT 400 WORDS)

Observations on the development of descending pathways from the brain stem to the spinal cord in the clawed toad Xenopus laevis

SummaryAnurans such as the clawed toad Xenopus laevis offer a unique opportunity to study the ontogeny of descending pathways to the spinal cord. Their transition from aquatic limbless tadpole to juvenile toad occurs over a protracted period of time during which the animal is accessible for experimental studies. In Xenopus laevis tadpoles the development of descending pathways has been studied from early limb-bud stage on (stage 50) with the aid of HRP slow-release gels. In stage 50, cells of origin of descending supraspinal pathways were already present throughout the reticular formation (including the interstitial nucleus of the fasciculus longitudinalis medialis) and in the vestibular nuclear complex. Also the giant Mauthner cells project to the cord at this stage. A spinal projection from the anuran homologue of the nucleus ruber of higher vertebrates does not appear before stage 58, i.e. when the hindlimbs are used for locomotion. Hypothalamospinal projections appear for the first time at stage 57. These observations in Xenopus laevis tadpoles suggest that reticulospinal and vestibulospinal projections innervate spinal segments very early in development, whereas the anuran red nucleus projects spinalward definitely later in development.

Materials and Techniques

The present cytoarchitectonic analysis of the brain stem of the savanna monitor lizard, Varanus exanthematicus (Fig. 1), is based on Nissl (cresylecht violet), Kluver-Barrera (1953), and Haggqvist (1936) stained material. Four transversely sectioned (15 µm) Nissl stained, one Kluver-Barrera, and one Haggqvist stained series were available. In addition, a Nissl and a Kluver-Barrera stained sagittal series (15 µm) were used. For comparison, transversely and sagittally sectioned series of the central nervous system of the tegu lizard, Tupinambis nigropunctatus, were available.

Comparative and Developmental Notes

Catecholamine (CA)-containing cells in the rostral midbrain tegmentum appear to be common to all tetrapods (see Parent et al. 1984b; Parent 1986). In reptiles and birds (see Sect. 3.1) the midbrain tegmentum contains a rather large number of CA cells that send their axons to the striatal regions of the telencephalon. In amphibians (Parent 1986), however, the rostral midbrain CA cell group is much less discrete than in amniotes, and no direct mesostriatal CA pathway has yet been demonstrated. In mammals, the topographical relationships between the pars compacta and the pars reticulata of the SN (Poirier et al. 1983; Parent 1986) and the development of the nuclei that form the VTA (Poirier et al. 1983; Halliday and Tork 1986) vary greatly among species. In Sect. 3.2 the cytoarchitecture, cytology, chemoarchitecture, and main fiber connections of the mammalian SN and VTA will be reviewed, with emphasis on data in rats and cats. Aspects of the development of these structures are discussed in Sect. 3.3.

Functional and Pathophysiological Considerations

Although it has been known for many years that various disturbances of movement and posture are associated with lesions in one or another of the basal ganglia (e.g., Wilson 1914; Denny-Brown 1960, 1962; Denny-Brown and Yanagisawa 1976; DeLong and Georgopoulos 1981), it is still not possible to account for individual symptoms, such as tremor, rigidity, or athetosis, in terms of normal or abnormal functioning of a particular component of the basal ganglia. Tremor cannot be produced in animals by lesions limited to structures of the basal ganglia. Neither electrolytic lesions of the SN nor 6-hydroxydopamine (6-OHDA) lesions of the ascending DAergic pathways from the SN and adjacent VTA produced tremor (Poirier 1960; DeLong and Georgopoulos 1981). It is only when lesions of the ascending cerebellar efferents are combined with nigrostriatal lesions that tremor appears. The usual site at which lesions are placed is in the VTA of the midbrain. Here, the lesions interrupt several pathways involving the SN and red nucleus: nigrostriatal, cerebellorubral, cerebellothalamic, and rubroolivary tracts. The conclusion is that parkinsonian rest tremor is not due to a purely striatal DA deficiency, but that damage to other structures, particularly the cerebellorubrothalamic projections, must also be involved. The ventrolateral thalamic nucleus has long been known to be involved in tremor generation (see I.S. Cooper et al. 1968). Hypokinesia and rigidity, cardinal features in Parkinson’s disease, are hypothesized to result from a complex series of changes resulting in an increase in basal ganglia output, particularly to the ventrolateral thalamic nucleus (DeLong and Georgopoulos 1981; Albin et al. 1989).

Organization and Connections of the Sensory Trigeminal Nuclei

The sensory part of the trigeminal nuclear complex comprises three nuclei: the descending (or spinal) nucleus, the principal nucleus, and the mesencephalic nucleus. The descending and principal nuclei constitute a column of gray which extends from the entrance of the trigeminal nerve into the rostral part of the spinal cord, where it is continuous with the peripheral part of the dorsal horn.

The Reticular Formation

The reticular formation of the reptilian brain stem is composed of various types of cells, ranging from small to very large, reticulospinal neurons (Sect. 13.1). It contains monoaminergic and peptidergic components (Sect. 13.2). The rhombencephalic reticular formation is the main site of termination of afferents from the spinal cord (see Sect. 4.2.1.1 and Fig. 22), is extensively afferented by the tectum mesencephali (see Sect. 10.1.3.2) and also receives a direct projection from the striatum (see Sect. 11.2 and Fig. 45). Efferent fibers pass to the thalamus and even to the telencephalon (Sect. 13.3), but chiefly to the spinal cord (Sect. 13.4). The bulk of descending pathways to the spinal cord is formed by reticulospinal fibers (ten Donkelaar 1982). Prosencephalic structures exert their influence on brain stem and spinal motor mechanisms via the brain stem reticular formation. It seems likely that, in reptiles and in other lower vertebrates (e.g., Nieuwenhuys 1977), the reticular formation represents a “final common supraspinal” pathway by way of which higher nervous centers can influence spinal motor mechanisms (ten Donkelaar 1982).

The Vestibular Nuclear Complex and Related Structures

The reptilian vestibular complex is usually divided into at least five nuclei (Weston 1936), i.e., the nucleus vestibularis dorsolateralis (also described as the superior vestibular nucleus: Beccari 1911 ; Larsell 1926; Stefanelli 1944a), the nucleus vestibularis ventrolateralis, the nucleus vestibularis tangentialis, the nucleus vestibularis ventromedialis, and the nucleus vestibularis descendens (or inferior: Beccari 1911; Stefanelli 1944a). In turtles, in addition a nucleus vestibularis superior can be distinguished as a subdivision of the dorsolateral vestibular nucleus (Weston 1936; Cruce and Nieuwenhuys 1974; Miller and Kasahara 1979; ten Donkelaar and Nieuwenhuys 1979; Bangma et al. 1983). Stefanelli (1944 a, b; see also Schwab 1979; ten Donkelaar and Nieuwenhuys 1979) noted the considerable differences in the development of the vestibular nuclei and their connections. The ventrolateral and dorsolateral vestibular nuclei are strongly developed in those reptiles with wholly or partly quadrupedal locomotion, whereas the tangential nucleus is particularly large in species with serpentine movements.

The Solitary Tract and Related Nuclei

The reptilian solitary tract is a well-developed, thin-fibered bundle that receives fibers from cranial nerves VII, IX, and X (see Sect. 6.2). Its fibers terminate in the nucleus of the solitary tract and in its mediocaudal extension, the nucleus commissurae infimae (Jacobs 1979; Barbas-Henry 1982; Barbas-Henry and Lohman 1984). In the older literature, based on normal material, an ascending pathway to a sensory visceral nucleus located in the rostral part of the rhomben-cephalon just ventromedial to the nucleus isthmi, has been suggested (Shanklin 1930; Barnard 1936; see also ten Donkelaar and Nieuwenhuys 1979). In a more recent study in Varanus exanthematicus, ten Donkelaar and de Boer-van Huizen (1981b) introduced the term “parabrachial region” for this secondary visceral center.