Anterograde Axonal Degeneration Research Articles

Synaptic relationships between axon terminals from the mediodorsal thalamic nucleus and layer III pyramidal cells in the prelimbic cortex of the rat

A combined study of anterograde axonal degeneration and Golgi electron microscopic technique was designed to examine the distribution and density of axon terminals from the mediodorsal thalamic nucleus (MD) over layer III pyramidal cells in the prelimbic cortex of the rat. The reconstructive analysis of serial ultrathin sections of gold-toned apical and basal dendrites of layer III pyramidal cells showed that degenerating thalamocortical axon terminals from MD formed asymmetrical synaptic contacts predominantly with dendritic spines of the identified basal dendrites as well as apical dendrites. There was little difference in the numerical density of thalamocortical synapses from MD per unit length of both apical and basal dendrites.

Connective integration of hippocampal grafts in excitotoxic hippocampal lesions in adult rats: an anterograde axonal tracing study

Exchange of nerve connections between developing neural grafts and adult recipient brains is enhanced for grafts placed in excitotoxic lesions, which spare recipient brain afferent axons in otherwise neuron-depleted lesion areas. In previous studies of hippocampal grafts placed in such lesions, we have used anterograde axonal degeneration, histochemical Timm staining and acetylcholinesterase to demonstrate host-graft interconnectivity. In this study, we have now used three anterograde axonal tracers, Phaseoulus vulgaris-leukoaglutinin (PHA-L), biocytin and biotinylated dextran amine (BDA), which allow individual fibers to be traced. Adult male rats with 1-week-old axon-sparing ibotenic acid lesions of the dorsal CA3 region or fascia dentata were grafted into the respective lesions with suspensions of fetal (El8-19) CA3 cells or a block of neonatal fascia dentata tissue. One to twelve months later, recipients were injected with Phaseoulus vulgaris-leukoaglutinin or biocytin in the hippocampus contralateral to the graft to trace the possible ingrowth and distribution within the transplants of host commissural axons, or into the transplants with biotinylated dextran amine in order to trace outgrowing graft fibers. In rats with succesfull host Phaseoulus vulgaris-leukoaglutinin or biocytin injections, the CA3 and fascia dentata transplants were innervated by labelled host commissural fibers. In the dentate transplants, most commissural fibers projected as normally to the inner part of the molecular layer, with fewer aberrant fibers extending more superficially into the molecular layer. Following injections into the fascia dentata and CA3 grafts of biotinylated dextran amine, labelled graft fibers were traced into the ipsilateral host dentate hilus, CA3 and CA1. From some CA3 containing grafts, a few labelled fibers were also observed passing through the host fimbria-fornix to the lateral septum on the grafted side. A few fibers were projected as far as to the most septal levels of the contralateral CA1.

Thalamocortical synapses between axons from the mediodorsal thalamic nucleus and pyramidal cells in the prelimbic cortex of the rat.

A combined anterograde axonal degeneration and Golgi electron microscopic (Golgi-EM) study was undertaken to identify thalamocortical synaptic connections between axon terminals from the mediodorsal thalamic nucleus (MD) and pyramidal cells in layers III and V of the agranular prelimbic cortex in the rat. The morphological characteristics of thalamocortical synapses from MD were also examined by labeling axon terminals with anterograde transport of wheat germ agglutinin-horseradish peroxidase (WGA-HRP). WGA-HRP labeled axon terminals from MD to the prelimbic cortex were small in size (0.5-1 microns in diameter), contained round synaptic vesicles, and formed axospinous synapses with asymmetrical membrane thickenings. With Golgi-EM methods, gold-toned apical dendrites in layer III were analyzed by reconstruction of serial ultrathin sections. Following lesions in the thalamus, degenerating thalamocortical axon terminals formed asymmetrical contacts exclusively on dendritic spines of the identified apical dendrites. More thalamocortical synapses were found on apical dendrites of layer V pyramidal cells than on apical dendrites of layer III pyramidal cells. In addition to thalamocortical synapses, a very few unlabeled symmetrical synapses were found on apical dendrites and somata of pyramidal cells, but they were not quantified and their sources are unknown.

Electron microscopic evidence that axon terminals from the mediodorsal thalamic nucleus make direct synaptic contacts with callosal cells in the prelimbic cortex of the rat

A combined study of anterograde axonal degeneration and HRP retrograde labeling has shown that there exist monosynaptic connections between afferent fibers from the mediodorsal thalamic nucleus (MD) and callosal cells in the prelimbic cortex of the rat. Degenerating axon terminals from MD made asymmetrical synaptic contacts with dendritic spines from apical dendrites of layer III pyramidal cells that were retrogradely labeled with HRP after its injection into the prelimbic cortex contralateral to MD lesions.

Change of phosphotyrosine immunoreactivity on microglia in the rat substantia nigra following striatal ischemic injury.

Using immunohistochemistry, we investigated changes in phosphotyrosine (P-Tyr) immunoreactivity on the microglia of the rat substantia nigra (SN) following striatal ischemic injury produced by transient middle cerebral artery (MCA) occlusion. Anterograde axonal degeneration in the SN due to striatal ischemic injury was detected by depletion of calcineurin immunoreactivity in that region from 1 day after operation. From 3 days to 1 month (the longest period examined in this study) after MCA occlusion, there was a significant increase in P-Tyr immunoreactivity in the SN ipsilateral to the MCA occlusion. Also, light microscopic observation showed that the microglia exhibited an increased immunoreactivity for P-Tyr and characteristic morphological changes in the ipsilateral SN. The present results indicate that a signal transducing cascade(s) associated with tyrosine phosphorylation may be involved in the activation of the microglia in the SN responding to anterograde degeneration of the striatonigral pathway.

Toxic neurofilamentous axonopathies and fast axonal transport. V. Reduced bidirectional vesicle transport in cultured neurons by acrylamide and glycidamide.

Fast axonal transport deficiencies as mechanisms of action of acrylamide in producing axonal degeneration are under evaluation. The current study determines the effects of acrylamide and several analogues on the number of vesicles moving within the neurite processes of cultured rat embryonic neurons. Acrylamide produced severe, concentration-dependent (0.25-1.0 mM) and time-dependent (0-60 min) reduction in the quantity of vesicles translocated in both the anterograde and retrograde directions. Glycidamide, a potential neurotoxic metabolite of acrylamide, produced a time-dependent but not a concentration-dependent (in the 0.25-1.0 mM range) reduction in bidirectional transport. Based on inhibition at 60 min, glycidamide was estimated to be 4 times more potent than acrylamide in altering transport. Propionamide, a C1-C2 saturated nonneurotoxic acrylamide analogue, had no effect on axonal transport. While a tendency for methylene bisacrylamide (MbACR) to reduce vesicle transport was noted, at the concentration used no statistically significant differences from control were observed. The data support the correlation between toxicant-induced fast anterograde and retrograde axonal transport reductions and axonal degeneration produced by acrylamide and its analogues.

CT changes associated with normal aging of the human brain

CT was used to measure changes in cerebral gray and white matter tissue densities associated with normal aging, using a cross-sectional design, in order to provide normative data for comparisons with abnormal aging such as dementias of Alzheimer's and vascular types. Cerebral compartmental densities were measured using plain CT, and their perfusion values were recorded during stable xenon inhalation (CT-CBF), among 81 neurologically and cognitively normal volunteers of different ages. Results led to the conclusion that cortical gray matter tissue densities progressively decline (polio-araiosis) after age 60. Cortical polio-araiosis is coupled with regional hypoperfusion but not with cortical atrophy. It is speculated that the cortical hypodensity identified by CT imaging parallels declines in cortical synaptic density, as reported from autopsy studies using anti-synaptophysin staining of cerebral cortex obtained from normal people above and below age 60. The coupling of cortical hypoperfusion with polio-araiosis is believed to reflect age-related reductions of cortical metabolic demands as reported by PET. During normal aging leuko-araiosis correlates directly with cortical atrophy, suggesting that anterograde axonal degeneration resulting from cortical neuronal dearborization play a role in its causation.

Microglial and astroglial reactions to anterograde axonal degeneration: a histochemical and immunocytochemical study of the adult rat fascia dentata after entorhinal perforant path lesions.

The reaction of microglial and a stroglial cells to anterograde axonal degeneration was studied in the fascia dentata of adult rats at various timepoints after removal of the entorhinal perforant path projection. Microglial cells were identified by histochemical staining for nucleoside diphosphatase (NDPase) at light and electron microscopical levels. Astroglial cells were stained immunocytochemically for glial fibrillary acidic protein (GFAP). Activated astroglial cells and some microglial cells also stained immunocytochemically for the intermediate filament protein vimentin. Phagocytotic activity was detected by histochemical staining for acid phosphatase. The postlesional connective reorganization of the cholinergic septohippocampal projection was monitored by histochemical staining for acetylcholinesterase. Twenty-four hours after entorhinal cortex ablation, microglial cells in the perforant path zones of the fascia dentata and the adjacent neuropil reacted by shortening and coarsening of processes and an increase in NDPase reactivity. These changes occurred prior to a noticeable increase in GFAP immunoreactivity and hypertrophy of astroglial cells (first evident on postlesional day 2) or sprouting of cholinergic septohippocampal fibres (first evident on day 3). There was evidence of an early, local proliferation of microglial cells in the denervated perforant path zones and migration into these zones of microglial cells from adjacent intact areas. The specific accumulation of strongly stained microglial cells within the denervated parts of the dentate molecular layer persisted for at least 4 weeks, while the astroglial reaction subsided at 3 weeks. The results demonstrate an early activation of microglial cells by axonal degeneration, and indicate that these cells may play a pivotal, inductive role in the subsequent glial and neural events.

Facial nerve fiber orientation, linkage between central nervous organization and muscular function.

Conflicting descriptions [1–9] of the anatomical organization of the facial nerve motor neurons have bee reconciled recently, through the use of neuroanatomical tracers [10–12] in combination with anterograde tracer and axonal degeneration techniques [13]. These observations have provided an anatomical basis for explaining some of the clinical phenomenon related to the facial nerve.

Direct synaptic connections between thalamocortical axon terminals from the mediodorsal thalamic nucleus (MD) and corticothalamic neurons to MD in the prefrontal cortex

A combined anterograde axonal degeneration with ibotenic acid and wheat germ agglutinin-horseradish peroxidase (WGA-HRP) retrograde tracing study revealed that some degenerating thalamocortical axon terminals from the mediodorsal thalamic nucleus (MD) directly formed asymmetrical synaptic contacts predominantly with dendritic spines of apical dendrites of WGA-HRP-labeled corticothalamic projection neurons to MD in the prelimbic cortex of the rat. This result suggests that there is a monosynaptic feedback loop from and to MD via deeper layer neurons in the prelimbic cortex.

Lesion of the rat entorhinal cortex leads to a rapid microglial reaction in the dentate gyrus

Stereotaxic lesioning of the entorhinal cortex leads to an anterograde axonal degeneration in the molecular layer of the dentate gyrus. As revealed by immunocytochemical and histochemical methods, lesion of the entorhinal cortex induced a proliferation of microglia and an increased expression of established microglial activation markers within the deafferented zone. Reactive microglial cells were detected as early as 24 h after the lesion. The microglial reaction showed a maximum around day 3 post-lesion and disappeared by day 8 post-lesion. Reactive microglia were strongly positive for the B4-isolectin from Griffonia simplicifolia (GSI-B4), expressed high levels of CR3 complement receptor and 5'-nucleotidase, but lacked CD4 and MHC class I and II antigens. In addition, microglial cells were identified using MUC 102, a new monoclonal antibody against rat microglia. At the ultrastructural level, reactive microglial cells were consistently seen to phagocytose degenerating terminals. Our data suggest that (1) axonal degeneration represents a sufficient stimulus for inducing microglial activation and proliferation in the deafferented dentate gyrus; (2) these activated microglial cells are characterized by immunophenotypes different from those observed in other types of CNS injury; (3) the early microglial reaction precedes the well-documented astrocyte reaction in the dentate gyrus; and (4) the timed interaction of microglia and astrocytes could be important for regulating regenerative sprouting processes in the mature CNS.

Enhanced host perforant path innervation of neonatal dentate tissue after grafting to axon sparing, ibotenic acid lesions in adult rats.

This study examines to which extent developing dentate granule cells grafted into excitotoxic lesions of the adult rat fascia dentata can be appropriately innervated by the host brain. The lesions were induced by focal injections of ibotenic acid (IA) and resulted in localized dentate and hippocampal neuronal cell death, but sparing of the afferent connections, now deprived of their targets. One week later pieces of fascia dentata from newborn rats were grafted into the lesions. After 6 weeks to 9 months the recipient brains were processed and analyzed by cell stain, histochemistry, immunohistochemistry, anterograde nerve fiber degeneration methods, and electron microscopy. Dentate grafts survived well in the lesion area and became organo-typically organized. They contained the normal nerve cell types of the fascia dentata and hilus (CA4), including the peptidergic somatostatin-, cholecystokinin- and enkephalin-reactive ones. The grafts were innervated by AChE-positive, cholinergic fibers from the host septum, and perforant path fibers from the host entorhinal area. The presence of the latter were demonstrated by Timm staining and light and electron microscopy of anterograde axonal degeneration. When the extent and density of the host perforant path innervation was examined and mapped at the electron microscopical level the grafts in the IA-lesions were found to receive a more extensive and denser host innervation than grafts placed in the normal fascia dentata of adult rats without a preceding axon-sparing ibotenic acid lesion. In this way the results demonstrate that certain lesion types can enhance the innervation of intracerebral grafts by already mature neural pathways of the point-to-point type.

Neural grafting to ischemic lesions of the adult rat hippocampus.

The purpose of this study was to examine the structural and connective integration of developing hippocampal neurons grafted to ischemic lesions of the adult rat hippocampus. The 4-vessel occlusion model was used to cause transient cerebral ischemia which damages CA1 pyramidal cells in the dorsal hippocampus, but spares nonpyramidal neurons and afferents in the area. One week later, cell suspensions were made from the CA1 region of fetal (E18-20) rats and injected stereotaxically into the lesion. The recipient brains were examined 6 weeks to 6 months later for survival, morphology, and intrinsic and extrinsic connections of the grafts. The methods used included cell stains, histochemical staining for acetylcholinesterase (AChE), immunocytochemical staining for neuropeptides (cholecystokinin (CCK), somatostatin (SS), enkephalin (Enk) and an astrocytic marker, glial fibrillary acidic protein (GFAP), as well as tracing by retrograde axonal transport of fluorochromes and light and electron microscopy of anterograde axonal degeneration. The grafts survived well (80%) and were often quite large. They were well integrated in the lesioned host brain area, contained both pyramidal cells and neuropeptidergic neurons and displayed a near normal GFAP immunoreactivity for astrocytes. The latter contrasted the dense gliosis of the host ischemic lesion. Judged by the AChE staining the grafts were innervated by cholinergic host septohippocampal fibers. Ingrowth of host hippocampal commissural fibers was demonstrated by Fink-Heimer staining for degenerating nerve terminals following acute lesions of the hippocampal commissures. At the ultrastructural level degenerating, electron dense terminals of host commissural origin were found even deep inside the graft neuropil in synaptic contact with mainly dendritic spines. A transplant efferent connection to the host brain was demonstrated by retrograde fluorochrome tracing and consisted of a homotypic projection to more posterior levels of the ipsilateral host CA1 and subiculum. Minor abnormal, efferent projections to the host dentate molecular layer were shown in Timm staining. We conclude that fetal CA1 neurons grafted to one week old ischemic lesions of the dorsal CA1 in adult rats become structurally well incorporated and can establish nerve connections with the host brain.

Enhanced sprouting of retinotectal fibers after early superior colliculus lesions in hamsters treated with gangliosides

The effects of exogenous gangliosides on sprouting of optic tract axons was studied in hamsters which, after a right tectal lesion on the day after birth (P1), had an abnormal retinotectal projection from the left eye to the left superior colliculus (SC). Sprouting of these axons was induced by removing the competing input by right eye removal on postnatal day 9 (P9). Intraperitoneal GM1, given daily and started on P9, significantly stimulated the sprouting response. This was demonstrated by Fink-Heimer silver staining of anterograde axonal degeneration three days after the left eye was removed on P36. Terminal fields in the left SC were, in average, twice as large compared to controls. An estimate of the total number of terminals (silver stained particles) revealed a value of 7.9 X 10(6) for GM1 and 3.2 X 10(6) for control hamsters, respectively. Diencephalic structures which also receive collateral input from the sprouting optic tract did not show any alterations in the size of the terminal field due to GM1-treatment, suggesting that, in vivo, gangliosides fail to initiate sprouting in areas that have not previously been denervated. Unexpectedly, GM1-treated hamsters also had significantly smaller right SC damage and less left damage near the midline. Subsequent reanalysis of the data based on a lesion-matching procedure indicates that effects on reducing atrophy were independent of the GM1-enhanced sprouting of retinofugal axons. These findings provide the first direct evidence that exogenous GM1 stimulates lesion-induced axon sprouting in the mammalian brain.

Intensive anti-oxidant pretreatment retards motor nerve degeneration

Intensive pretreatment of cats with a combination of the antioxidants d-α-tocopherol (200 IU) and selenium (50 μg) once daily for 5 days (p.o.) was found to significantly preserve the functional capacity of degenerating soleus motor nerve terminals (measured at 48 h after axon section at the hip) in the in vivo saoleus nerve-muscle preparation. The preservation of function was apparent in terms of: (a) a greater seleus contractile response to nerve stimulation at low frequencies, (b) a more rapid recovery from d-tubocurarine-induced neuromuscular block, and (c) a better maintenace of tetanic contractile tension during high-frequency nerve stimulation. The ability of antioxidants to retard the anterograde axonal degeneration (i.e. ‘Wallerian’) process suggests that lipid peroxidation may be a fundamental mechanism of neuronal degeneration.

Intracephalic transplants of freeze-stored rat hippocampal tissue.

The survival and cellular and connective organization of intracephalic transplants of developing, freeze-stored rat hippocampal tissue were examined. Blocks of tissue containing the hippocampus and fascia dentata were obtained from late embryonic (E16-E22) and early postnatal rats (P0-P4) and immersed in a tissue culture medium with 10% of the cryoprotective agent DMSO, frozen at a cooling rate of approximately 1 degree C/minute, and stored for 1-226 days in liquid nitrogen. After quick thawing and washing out of the DMSO the tissue blocks were transplanted to the brain of adult rats. From 2 weeks to 3 months later the recipient brains were processed histologically. The cellular and connective organization of the transplants and their interaction with the host brains were analyzed after thionin cell staining, Timm's staining for hippocampal and dentate afferents, immunohistochemical staining for enkephalin-, CCK-, and somatostatin-reactive neurons and afferents, AChE staining for cholinergic afferents, and silver stains for fiber architectonics and tracing of connections by anterograde axonal degeneration. Freeze-storage narrowed the range of donor ages with good transplant survival. The best surviving hippocampal and dentate transplants thus came from 17-21-day-old embryos. There was no correlation between the length of storage and survival. Structurally the transplants of stored tissue were more frequently fragmented than the transplants of fresh tissue when located outside the brain parenchyma in the brain ventricles. This was in accordance with the results of a previous study of grafts of freeze-stored and fresh hippocampal tissue placed in the anterior eye chamber. Despite the decrease in survival and the tendency for fragmentation many well-structured and organotypically organized hippocampal and dentate transplants were recovered corresponding to the donor ages E19-E21. In addition to the main cell types (granule cells and pyramidal cells) the freeze-stored transplants also contained peptidergic nerve cells reacting for CCK, somatostatin, and enkephalin. The organization of the intrinsic nerve connections and the exchange of connections with the host brain were similar for transplants of stored and fresh tissue. Besides the consistent innervation of the hippocampal and dentate transplants by host cholinergic afferents monitored by AChE staining, several appropriately located dentate transplants thus sent mossy fibers to the host CA3. Others received host perforant path projections. A CA3-associated transplant projection to the denervated perforant path zones in the host fascia dentata was also observed.(ABSTRACT TRUNCATED AT 400 WORDS)

Acoustic chiasm II: Anatomical basis of binaurality in lateral superior olive of cat.

The afferent projections to the lateral superior olive (LSO) were examined with horseradish peroxidase, horseradish peroxidase-wheat germ agglutinin conjugate, 125I-wheat germ agglutinin and tritiated leucine autoradiograhy, anterograde axonal degeneration, and 14C-2-deoxyglucose methods. The pathway to the ipsilateral LSO orginates in the spherical cells in anteroventral cochlear nucleus. Although some of the fibers pass above the lateral nucleus of the trapezoid body, most pass below it and turn at right angles to enter the LSO either directly through its ventral, lateral, or dorsal borders, or through its ventral or dorsal hilus. They end in unpolarized terminal fields throughout the LSO. Most if not all of these fibers are true collaterals of axons continuing across the midline in the trapezoid body. Verifying Held's (1893) finding of a major direct projection from the cochlear nucleus to the contralateral medial nucleus of the trapezoid body (MTB) and Rasmussen's ('46) finding of a major projection from the MTB to the LSO, the present results illustrate that this two-neuron pathway probably supplies all but a very small component of the relatively direct input to the LSO from the contralateral ear. This pathway originates in the globular cells of the ventral cochlear nucleus and relays mostly though not exclusively through the "principal cells" in the more rostral parts of the MTB. It terminates mostly in perisomal endings in unpolarized fields throughout the LSO, though most heavily within the (high frequency) medial and middle limbs and less heavily in the LSO's (low frequency) lateral limb. In addition to this indirect pathway, there is a small direct pathway to the contralateral LSO as suggested by Goldberg and Brown ('69) and Warr ('72, '82). This direct pathway to the contralateral LSO, like the direct ipsilateral pathway, probably originates in the spherical cell region of the ventral cochlear nucleus, crosses the midline in the trapezoid body, and terminates in a small circumscribed area within the LSO's ventromedial (high frequency) area. The 2-deoxyglucose method applied to cats in which the ipsilateral and contralateral pathways have been surgically isolated shows that each of the pathways converging on the LSO is topographically and tonotopically organized with the ipsilateral and the combined contralateral terminations in strict tonotopic register.

Retinofugal projections of the big brown bat, Eptesicus fuscus and the neotropical fruit bat, Artibeus jamaicensis.

Retinal connections were studied in Eptesicus fuscus and Artibeus jamaicensis using anterograde axonal degeneration and autoradiographic techniques following unilateral enucleations and uniocular injections of radioactive amino acids. Although each retina projected bilaterally to the brainstem, the number of silver grains in the emulsion of autoradiographs indicated that nearly all fibers in the optic nerve entered the contralateral optic tract. Ipsilaterally, a major portion of the projection ended in the suprachiasmatic nucleus; caudal to the suprachiasmatic nucleus, the amount of label was so small that individual silver grains were counted to determine the location and quantity of label in other ipsilateral nuclei. In both species the retinal projection terminated bilaterally in the suprachiasmatic, dorsal lateral geniculate, ventral lateral geniculate, and pretectal olivary nuclei and contralaterally in the posterior pretectal nucleus, superficial gray layers of the superior colliculus, and nuclei of the accessory optic system. In Eptesicus the projection to the nucleus of the optic tract ended contralaterally, and in Artibeus it ended in this nucleus bilaterally. The results of this study revealed a basic theme in the optic projection of the two ecologically different microchiropterans. The results differed, however, in that the projection was larger and visually related nuclei were better developed in Artibeus. Such variations are presumed to relate to eye size and the relative use of vision by the two chiropterans.

The auditory brainstem nuclei and some of their projections to the inferior colliculus in the North American opossum

Afferent projections to the inferior colliculus in the North American opossum have been examined using the retrograde transport of horseradish peroxidase. Projections to primarily the contralateral inferior colliculus arise in the dorsal and ventral cochlear nuclei, the auditory nerve nucleus and the spinal trigeminal nucleus pars caudalis, while ipsilateral projections arise in the superior paraolivary nucleus, the ventral nucleus of the trapezoid body, the ventral nucleus of the lateral lemniscus, the paralemniscal nucleus, the deep layer of the superior colliculus and the parabrachial nucleus. Bilateral projections to the inferior colliculus originate within the dorsal column nuclei, the nucleus reticularis gigantocellularis pars ventralis, the lateral and medial superior olivary nuclei, the dorsal nucleus of the lateral lemniscus and the auditory cortex. Nissl, fiber and Golgi-stained preparations were used to study the neuronal organization of those auditory nuclei with projections to the inferior colliculus. Anterograde axonal degeneration and transport techniques revealed that the inferior colliculus is innervated differentially by the dorsal and ventral cochlear nucleus, the superior olivary complex and the auditory neocortex. Axons from the contralateral dorsal cochlear nucleus and the ipsilateral superior olivary complex innervate both the central nucleus and external cortex, whereas those from ventral cochlear nucleus and contralateral, superior olivary complex project to only the central nucleus. Projections from auditory cortex form the complement of those from the cochlear nuclei and superior olivary complex, that is, they terminate in a thin band overlying the dorsal cortex and the superficial layer of external cortex. Our results have been compared with those obtained from eutherian mammals and it is clear that there are striking similarities in neuronal organization and connectivity. Since the opossum is born 12 days after conception and has an extended development in an external pouch, it may be suited for developmental studies of the mammalian auditory connections and the behaviors dependent of them.

Afferents to oculomotor nuclei from area "Y" in Macaca mulatta: an anterograde degeneration study.

AbstractElectrolytic lesions were placed in the dentate and interpositus nuclei of the monkey M. mulatta and the resulting anterograde degeneration was stained with the Wiitanen or Nauta‐Laidlaw techniques. Two of 19 lesions produced preterminal degeneration in the oculomotor nuclei. In both cases the lesions also damaged vestibular area “y” subjacent to the rostral pole of the dentate nucleus. The course and terminal distribution of anterograde degeneration to the oculomotor nuclei was the same in both cases. Degenerating fibers were found in lateral parts of the ipsilateral MLF, and preterminal degeneration was found in the ipsilateral abducens and trochlear nuclei and the dorsal subdivision of the oculomotor nucleus. Degenerating fibers were also traced from the crossed brachium conjunctivum to the contralateral paramedian subdivision of the oculomotor nucleus. These fibers appeared to course in dorsomedial parts of the brachium. Lesions of the dentate and interpositus nuclei which did not damage area “y” produced no anterograde axonal degeneration in the MLF or the oculomotor nerve nuclei. The results are discussed with regard to previous reports of cerebello‐oculomotor fibers originating in the dentate and interpositus nuclei. The results suggest that area “y”, rather than the cerebellar nuclei, projects principally to oculomotor neurons that control vertical eye movements.