The isolation and transplantation of the brain. An historical perspective emphasizing the surgical solutions to the design of these classical models.

Following an historical review of earlier attempts to develop separated head and brain preparations and their contributions to modern-day understanding of the neurophysiology and neurochemistry of the central nervous system, the experiments that eventually led to the first successful total isolation of the mammalian brain are presented. The operative strategies emphasizing the anatomical and physiological problems requiring solution that resulted in vascular and neurogenic separation from the parent body and cephalon are described. The innovative engineering concepts that were utilized in the design of miniaturized equipment to maintain the isolated brain in a living state under conditions of cross circulation, extracorporeal artificial perfusion and transplantation are elaborated. Investigations employing isolated brain and cephalic preparation documenting tissue substrate requirements, metabolic and rheological conditions prevailing at various low temperatures and the immunologically privileged state of the separated organ are briefly presented. The unique opportunities these isolated brain models offer for study are emphasized as well as the complexity of their surgical preparation, which, to date, has limited their universal applications.

Projection systems and terminal localization of dorsal column afferents: an autoradiographic and horseradish peroxidase study in the rat.

Projection systems from the gracile nucleus and the cuneate nuclear complex to their terminal sites in the mesencephalon, diencephalon, and cerebellum were examined by means of anterograde autoradiography and retrograde horseradish peroxidase methods. Three projection systems emerge from the dorsal column nuclei, decussate via internal arcuate fibers, and form the contralateral medial lemniscus (ML). At the obex, some fibers split off the ML and course dorsolaterally, forming an ascending lateral system which fits the "lemniscal adjunct channel" (LAC) concept of Graybiel ('72). The ML continues rostrally as the "main lemniscal line channel" (MLLC). At the inferior colliculus, some LAC fibers terminate in the pontine nuclei, parabrachial, dorsal reticular nuclei, and the external and ventral medial part of the central nucleus of the inferior colliculus. More rostrally at the level of the superior colliculus, terminal fields are found in the medial nucleus of the medial geniculate body, the suprageniculate, pretectal, and mesencephalic reticular nuclei, marking the end of the LAC. In the diencephalon, gracile fibers leave the MLLC and form a crescentlike terminal field along the extreme lateral border of the ventral posterior lateral nucleus (VPL) of the thalamus. Cuneate MLLC fibers terminate in a bandlike formation in the VPL medial to the gracile termination. The third fiber system, the cuneocerebellar projection, emerges from the cuneate, the external cuneate nuclei, and the "cellular bridge" and immediately enters the ipsilateral inferior cerebellar peduncle. Upon entering the cerebellum, the major fiber component remains ipsilateral and terminates as vertical bands in vermal and paravermal lobules, and lobules I through IVa. The posterior cerebellar lobe contains terminal bands in lobules VII-IX, the copula pyramidis, and the paramedian lobule. It is concluded that the dorsolateral fiber system conforms to Graybiel's LAC. It is more divergent and probably less modality specific, whereas the medial lemniscal system conforms to the MLLC, which is said to be modality specific, less divergent, and locked to specific sensory-motor response characteristics. The topography of cerebellar terminal bands indicates that there is sensory-motor representation from all parts of the body to all parts of the cerebellum, at least in the rat.

Brain stem projections from cortical area 18 in the albino rat.

Efferent brain stem projections from area 18 of the albino rat cortex were traced by autoradiography. Since results could have been compromised by spread of injected label to neighboring areas 17 and 29, studies of projections from these areas were used as controls. A hitherto unreported projection from area 18 to the thalamus in the region of its anterior nuclei was found, terminating in a roughly circular area including parts of the anteromedial, ventral, ventromedial and rhomboid nuclei. At this same level, a very light projection was seen in the contralateral anteromedial nucleus. More caudally the projection pattern was similar to that of area 17, with the lateral, lateral posterior, posterior and pretectal nuclei as targets. However, area 18 showed no projections to either division of lateral geniculate nucleus, projections which are commonly seen following injections in area 17. More caudally, the area 18 projection to the superior colliculus was confined to its four deepest laminae, a projection identical to that from areas 29c and 29b. Area 18 also resembled the cingulate cortex in that it sent a small projection to the dorsolateral central gray, although the routes taken to this region were slightly different. It was decided that the projections from this visual association area were, for the most part, unique to that area, although some of them resembled those from either the cingulate cortex or the primary visual area.

Cerebellothalamic projections in the rat: an autoradiographic and degeneration study.

The purpose of this study was to determine the topographical organization of cerebellothalamic projections in the rat. Following stereotaxic injections of 3H-leucine or electrolytic lesions in the cerebellar nuclei, efferent fibers were observed to emerge from the cerebellum through two discrete routes. Fibers from the fastigial nucleus decussated within the cerebellum, formed the crossed ascending limb of the uncinate fasciculus, ascended in the dorsal part of the midbrain tegmentum, and entered the thalamus. Cerebellothalamic fibers from the interpositus and dentate nuclei coursed in the ipsilateral brachium conjunctivum, decussated in the caudal midbrain, and ascended to the thalamus via the crossed ascending limb of the brachium conjunctivum. Cerebellar terminations were observed in the intralaminar, lateral, and ventral tier thalamic nuclei as well as in the medial dorsal nucleus. Projections to the intralaminar nuclei were more pronounced from the dentate and posterior interpositus than from the anterior interpositus and fastigial nuclei. The lateral thalamic nuclei received a projection from the dentate and posterior interpositus nuclei while the fastigial nucleus projected to the medial dorsal nucleus. Within the rostral ventral tier nuclei fastigiothalamic terminations were localized in the medial parts of the ventral medial and ventral lateral nuclei, whereas dentatothalamic projections were concentrated in the lateral parts of the ventral medial nucleus and the medial half of the ventral lateral nucleus. Terminations from the posterior interpositus nucleus were observed ventrally and laterally within the caudal two-thirds of the ventral medial nucleus and throughout the ventral lateral nucleus, where they were densest in the lateral part of its lateral wing and within the central part of its cap. The anterior interpositus nucleus also projected to the central and lateral parts of the ventral lateral nucleus, but these terminations were considerably less dense than those from the posterior interpositus. A few fibers from the interpositus nuclei terminated in the medial part of the rostral pole of the ventral posterior nucleus. A prominent recrossing of cerebellothalamic fibers from the fastigial, posterior interpositus, and dentate nuclei occurred through the central medial nucleus of the internal medullary lamina. These terminated within the ipsilateral ventral lateral and intralaminar nuclei. These results show that each of the cerebellar nuclei project to the thalamus and that their terminations are topographically organized in the rostral ventral tier nuclei. The clustering of autoradiographic silver grains or terminal degeneration observed in the thalamic nuclei suggests a medial-to-lateral organization of this cerebellothalamic system.

Nigrothalamic pathway in the cat demonstrated by autoradiography and electron microscopy.

Light microscopic autoradiography and electron microscopy were used to trace the nigrothalamic projections and to study the sites of termination of this pathway in the cat. Injections of tritiated amino acids or electrolytic lesions were placed in the substantia nigra pars reticularis (SNr). An accumulation of radioactivity was found in the ventral medial nucleus and in the ventromedial part of the ventral anterior nucleus. At the ultrastructural level degenerating medium size synaptic boutons and medium size myelinated fibers were observed in these nuclei. The boutons contained clear pleomorphic veiscles and formed symmetrical type synaptic contacts with regular type dendrites and vesicel-containing dendrites. The present findings indicate that the ventral medial nucleus is the principal site of termination of nigrothalamic projections in the cat.

The anatomical organization of the cerebello-olivary projection in the cat.

The cerebello-olivary pathway in the cat has been examined using orthograde and retrograde neuroanatomical tracing techniques. The orthograde transport of 3H-leucine from injection sites in the deep cerebellar nuclei labeled dentate and interpositus projections to the rostral two-thirds of the contralateral inferior olivary complex. These projections are topographically organized, with the dentate nucleus projecting to the principal olivary nucleus and the posterior and anterior interpositus nuclei projecting to the medial and dorsal accessory olives respectively. Fibers from the ventral half of the dentate nucleus terminate in the lateral bend and ventral lamina of the principal olive, whereas the medial and lateral parts of the dorsal half of the nucleus project to the medial and lateral regions of the dorsal lamina respectively. It is apparent that the more caudal parts of the interpositus nuclei project to areas of the medial and dorsal accessory olives near the caudal end of the principal olivary nucleus, whereas neurons in the more rostral parts of the interpositus nuclei project to the more rostral areas of the accessory olivary nuclei. A connection between the fastigial ncleus and the inferior olive could not be demonstrated. The retrograde transport of horseradish peroxidase (HRP) from injections sites in the inferior olive labeled cells throughout the contralateral dentate and interpositus nuclei. The labeled cells were especially numerous in the ventral parts of the dentate and posterior interpositus nlclei. These HRP-positive neurons were consistently small (10--15 mu) ovoid or spindle-shaped cells, with relatively large nuclei and light-staining Nissl substance. This evidence strongly suggests that the cerebello-olivary pathway originates from a population of small neurons in the dentate and interpositus nuclei and projects to specific, topographically defined areas in the contralateral inferior olive.