Walle J. H. Nauta

Efferent connections of the substantia nigra and ventral tegmental area in the rat

Small injections of tritiated leucine and proline confined to the ventral tegmental area (AVT) were found to label fibers ascending: (a) to the entire ventromedial half of the striatum, but most massively to the ventral striatal zone that includes the nucleus accumbens; (b) to the thalamus: lateral habenular nucleus, nuclei reuniens and centralis medius, and the most medial zone of the mediodorsal nucleus; (c) to the posterior hypothalamic nucleus and possibly the lateral hypothalamic and preoptic region; (d) to the nuclei amygdalae centralis, lateralis and medialis; (e) to the bed nucleus of the stria terminalis, the nucleus of the diagonal band, and the medial half of the lateral septal nucleus; (f) to the anteromedial (frontocingulate) cortex; and (g) to the entorhinal area. Further AVT efferents descend to the medial half of the midbrain tegmentum including an anterior region of the median raphe nucleus, to the ventral half of the central grey substance including the dorsal raphe nucleus, to the parabrachial nuclei, and to the locus coeruleus. Similar injections centered in the pars compacta of the substantia nigra (SNC) label fibers that are distributed in the striatum in an orderly medial-to-lateral arrangement, and almost entirely avoid the nucleus accumbens and olfactory tubercle. With the exception of the lateral quarter of the substantia nigra, which apparently does not project to the extreme rostral pole of the striatum, each small SNC locus, regardless of its anteroposterior localization, distributes nigrostriatal fibers throughout the length of the striatum. Descending SNC efferents are distributed to the same general regions that receive descending AVT projections, except that no SNC fibers appear to enter the locus coeruleus. Isotope injections confined to the pars reticulata (SNR) label sparse nigrostriatal fibers, and numerous nigrothalamic fibers ascending mainly to the nucleus ventromedialis and in lesser number to the parafascicular nucleus and the paralamellar zone of the nucleus mediodorsalis. Descending SNR fibers leave the nigra as a voluminous fiber bundle that bifurcates into a large nigrotectal and a smaller nigrotegmental component, the latter terminating largely in the pedunculopontine nucleus of the pontomesencephalic tegmentum.

The amygdalostriatal projection in the rat—an anatomical study by anterograde and retrograde tracing methods

Tritiated leucine and proline injected into the amygdaloid complex was found to label a voluminous amygdalostriatal fiber system which is distributed to all parts of the striatum except an antero-dorsolateral striatal sector. The connection is established by way of the longitudinal association bundle as well as the stria terminalis, and includes a modest (10-15%), symmetrically distributed contralateral component conveyed by the anterior commissure. Both autoradiographic findings and subsequent observations in retrograde cell-labelling (horseradish peroxidase) material indicate that the amygdalostriatal projection originates mainly from the nucleus basalis lateralis amygdalae, in much lesser volume from the nucleus basalis medialis, and minimally from the nucleus lateralis amygdalae; no other contributing amygdaloid cell group could be identified. A comparison of the present findings with earlier reports indicates that the amygdalostriatal projection widely overlaps the striatal projections from the ventral tegmental area, the mesencephalic raphe nuclei and the prefrontal cortex. Like the amygdalostriatal projection, these striatal afferents largely or entirely avoid the antero-dorsolateral striatal quadrant, which thus appears to be the striatal region most sparsely innervated by afferents originating from structures within the circuitry of the limbic system. Findings in additional autoradiographic material identify this relatively non-limbic striatal quadrant as the main region of distribution of the corticostriatal projection from the sensorimotor cortex.

SILVER IMPREGNATION OF DEGENERATING AXONS IN THE CENTRAL NERVOUS SYSTEM: A MODIFIED TECHNIC

Frozen sections of formalin-fixed brains containing surgical lesions, were treated with 15% ethanol for 0.5 hr., soaked in 0.5% phosphomolybdic acid for 0.25–1.0 hr., and subsequently treated with 0.05% potassium permanganate for 4–10 min. (The duration of the latter treatment is critical and individually variable). Subsequent procedure is as follows: decolorize in a mixture of equal parts of 1% hydroquinone and 1% oxalic acid; wash thoroughly and soak sections in 1.5% silver nitrate for 20–30 min.; ammoniacal silver nitrate (silver nitrate 0.9 g., distilled water 20 ml., pure ethanol 10 ml., strong ammonia 1.8 ml., 2.5% sodium hydroxide 1.5 ml.) 0.5–1.0 min.; reduce in acidified formalin (distilled water 400 ml., pure ethanol 45 ml., 1% citric acid 13.5 ml., 10% formalin 13.5 ml.) 1 min.; wash, and pass section through 1% sodium thiosulfate (0.5–1.0 min.); wash thoroughly and pass sections through graded alcohols and xylene (3 changes); cover in neutral synthetic resin.

The Problem of the Frontal Lobe: A Reinterpretation

The frontal lobe, despite decades of intensive research by physiologists, anatomists and clinicians, has remained the most mystifying of the major subdivisions of the cerebral cortex. Unlike any other of the great cerebral promontories, the frontal lobe appears not to contain a single sub-field that could be identified with any particular sensory modality, and its entire expanse must accordingly be considered association cortex. It should, perhaps, not be surprising in view of this circumstance alone that loss of frontal cortex, in primate forms in particular, leads to a complex functional deficit, the fundamental nature of which continues to elude laboratory investigators and clinicians alike. The purpose of this paper is, to review some aspects of this deficit in animals and man, and to inquire to what extent the consequences of frontal-lobe lesion can be evaluated in neurological terms.

Projections of the Lentiform Nucleus in the Monkey

Summary The fiber degenerations resulting from variously located lesions of the lentiform nucleus were studied in the rhesus monkey by the aid of the Nauta-Gygax and Albrecht-Fernstrom techniques. The following observations were made. o (1) Putaminofugal connections. Thin fibers originating in the putamen and composing Wilsons ‘pencil’ bundles traverse the globus pallidus, converging toward the medial point of the lentiform nucleus. The mjority of these fibers terminate in both segments of the globus pallidus, but a considerable number continue caudalward, perforating the cerebral peduncle as ventral components of Edingers comb system, and terminate in lateral parts of the substantia nigra, pars reticulata. (2) Pallidofugal connections. The ansa lenticularis as defined by von Monakow originates exclusively from the globus pallidus. Its middle division, composed of fibers of medium calibre, arises in the external pallidal segment and traverses the cerebral peduncle as the dorsal component of the comb system to end in the subthalamic nucleus. The thick-fibered dorsal and ventral ansal divisions arise in the internal pallidal segment and combine to form the fasciculus lenticularis which represents the only apparent direct connection of the globus pallidus with the thalamus and the mesencephalic tegmentum. o (a) Pallidothalamic fibers follow successively the lenticular and thalamic fasciculi and are distributed to the nuclei ventralis lateralis (subnuclei medialis and oralis of Olszewski and Baxter; none to Zone X and subnucleus caudalis) and ventralis anterior (except subnucleus VAmc). A considerable number of thinner fibers, possibly collaterals of those to VL and VA, terminate in the ‘centre median’; this connection appears to close a potential transthalamic circuit: putamen-globus pallidus-‘centre median’-putamen. (b) There is suggestive evidence of pallidofugal fibers following the stratum zonale thalami to the habenula. (c) Pallidohypothalamic connections could not be identified. Most, and possibly all, of the ansal fibers composing the so-called pallidohypothalamic tract loop back into Forels fields after a shorter or longer descent into the hypothalamus. (d) Fibers of the fasciculus lenticularis by-passing the thalamus are distributed to the nucleus of Forels field H (prerubral field). Longer fibers of the same category pass caudalward lateral and ventral to the red nucleus and terminate in the nucleus tegmenti pedunculopontinus, particularly in the latters caudal subnucleus compactus (terminology of Olszewski and Baxter). A few such pallidomesencephalic fibers appear to end in a small circumscript caudal area of the substantia nigra, pars compacta. No evidence was obtained of pallidotegmental fibers extending caudally beyond the mesencephalon. (e) Pallidal efferents to the zona incerta could not be identified. Only sporadic pallidofugal fibers could be followed to the red nucleus, nucleus interstitialis, and nucleus of Darkschewitsch.

Columnar Distribution of Cortico-Cortical Fibers in the Frontal Association, Limbic, and Motor Cortex of the Developing Rhesus Monkey

The terminal distribution of cortico-cortical connections was examined by autoradiography 7-8 days following injections of tritium labeled amino acids into the dorsal bank of the principal sulcus, the posterior part of the medial orbital gyrus, or the hand and arm area of the primary motor cortex in monkeys ranging in age from 4 days to 5.5 months. Labeled axons originating in these various regions of the frontal lobe have topographically diverse ipsilateral and contralateral destinations but virtually all of these projections share a common mode of distribution: they terminate in distinct vertically oriented columns, 200-500 mum wide, that extend across all layers of cortex and alternate in regular sequence with columns of comparable width in which grains do not exceed background. Spatial periodicity in the pattern of transported label in such regions as the prefrontal association cortex, the retrosplenial limbic cortex and the motor cortex indicates that columination in the intracortical distribution of afferent fibers is not unique to sensory specific cortex but is instead a general feature of neocortical organization. A columnar mode of distribution of cortico-cortical projections is present in monkeys at all ages investigated but is especially well delineated in the youngest of them. Thus, grain concentrations within columns are very high in monkeys injected at 4 days of age, somewhat lower in monkeys injected at 39-45 days of age, and least dense in those injected at 5.5 months. The distinctness of the spatially segregated pattern of innervation in the cortex of neonates indicates that the columnar organization of association-fiber systems in the frontal and limbic cortex is achieved before or shortly after birth.

The hypothalamic distribution of the stria terminalis in the rat

Abstract The hypothalamic distribution of the stria terminalis was studied by the Fink-Heimer methods and electron microscopy in rats sacrificed 3–6 days after unilateral amygdalectomy or stria terminalis section. Each of the major hypothalamic stria components was found to be distributed to fairly sharply defined regions, as follows: (1) The postcommissural component terminals massively in the rostral half of the anterior hypothalamic nucleus; an apparently small number of its fibers join the medial forebrain bundle. (2) The supracommissural component terminates predominantly in a dense synaptic zone surrounding the ventromedial nucleus and containing a massive plexus dendrites protruding from this nucleus, in smaller quantity also in lateral and ventral parts of the ventromedial nucleus proper and in the ventral premammillary nucleus. The prevalence in the hypothalamus of neurons with long dendrites suggests that the stria terminalis may have synaptic contracts not only with perikarya and dendrites of neurons lying within its synaptic fields, but also with dendrites of neurons whose cell bodies lie well outside these fields.

A General Profile of the Vertebrate Brain, with Sidelights on the Ancestry of Cerebral Cortex

The most elementary tenet of the theory of evolution is that animal specification followed a temporal sequence such that one order of species developed from another, and in time gave rise to one or more further orders. The reconstruction of the “tree of evolution,” one of the most constantly pursued goals of biology, is attended by numerous difficulties, foremost among which is the circumstance that existing forms of life represent little more than “leaves on the ends of branches” of a tree, the trunk and limbs of which have long been extinct. Virtually all extant animals appear to be specialized forms that have diverged in greater or lesser degree from any of the identified or presumed mainlines of evolution. The identification of such “mainlines,” furthermore, is often highly uncertain, the more so because several vertebrate classes appear to have evolved not from one, but from several ancestors. Modern amphibians, for example, are suspected of representing several developmental lines originating from various piscine forms.

A note on the problem of olfactory associations of the orbitofrontal cortex in the monkey

Abstract Evidence has recently been reported suggesting (1) that a circumscript posterolateral region of the monkeys orbitofrontal cortex has the functional significance of a higher-order olfactory association cortex (2) that olfactory information is conveyed to this cortical region over a conduction route that by-passes the thalamus. The present paper reports an attempt to identify sources of afferents to the above region that conceivably could function as links in such a specific olfacto-frontal conduction route. The attempt was made by comparing the patterns of retrograde cell-labelling resulting from horseradish peroxidase injections confined to, respectively, the lateroposterior quadrant of the orbitofrontal cortex and a more anterior orbitofrontal region with each other and with published reports of similar studies involving the frontal convexity. Both orbitofrontal injections labelled numerous cells in the medial subdivision of the nucleus mediodorsalis, and lesser numbers of cells in the nucleus ventralis anterior thalami, in the basal amygdaloid nuclei, substantia innominata, and temporal isocortex. Only in the case of injection in the lateroposterior quadrant of the orbitofrontal cortex did a considerable number of additional labelled cells appear in the medial bank of the rhinal sulcus (prorhinal cortex of Van Hoesen and Pandya). Since the prorhinal cortex lies in the path of known olfactory circuitry, this finding suggests that it gives rise to an olfactory conduction route selectively directed at the lateroposterior orbitofrontal cortex.

The thalamic projection to cortical area 17 in a congenitally anophthalmic mouse strain

Abstract The thalamocortical projection innervating area 17 in the congenitally anophthalmic ZRDCT-An mouse was compared with its counterpart in normal-eyed mice of different strains by the horseradish peroxidase method. The results indicate that, despite absence of retinal afferents and a reduction of its neuronal population to 76% of normal, the dorsal nucleus of the lateral geniculate body in the ZRDCT-An mouse projects to area 17 in an essentially normal topographic pattern. Our evidence also indicates the existence, both in normal-eyed and ZRDCT-An mice, of an extrageniculate thalamocortical projection to area 17, arising in particular from the nucleus lateralis posterior but in lesser degree also from the nucleus lateralis dorsalis. In both normal and anophthalmic mice, this extrageniculate projection favors the lateral and posterior parts of area 17; however, the projection to these parts is considerably greater in the congenitally anophthalmic than in the normal-eyed mouse. Compensatory innervation thus appears to occur in the anophthalmic mouse not only at the level of the primary retinorecipient nucleus of the geniculostriate system, but also at the level of the visual cortex that is once removed from the direct effects of congenital denervation.