Projections of the cerebellar and dorsal column nuclei upon the inferior olive in the rhesus monkey: an autoradiographic study.

Projections from the cerebellar and dorsal column nuclei to the inferior olive of the rhesus monkey were traced with anterograde autoradiographic methods. The cerebellar nuclei give rise to a massive projection which reaches the contralateral inferior olivary complex by way of the descending limb of the superior cerebellar peduncle. Dentato-olivary fibers project exclusively upon the principal olivary nucleus (PO) and observe a strict topography. The dorsal, lateral, and ventral dentate project respectively to the dorsal, lateral, and ventral lamellae of the PO. Within the lamellae, the dentato-olivary fibers are related point for point in the medio-lateral axis. By contrast, the rostro-caudal topography is reversed so that the rostral pole of the dentate projects to the caudal PO and the caudal dentate to the rostral PO. These connections are predominantly crossed but a small ipsilateral component recrosses the midline at the olivary commissure and mirrors the topography on the opposite side. The anterior interpositus projects only to the medial half of the DAO and the posterior interpositus projects only to the rostral two thirds of the MAO. The ipsilateral component is minor in comparison with the contralateral projection, but appears to be more substantial than the ipsilateral projection to the PO arising from the dentate nucleus. The fastigial nucleus does not project upon the olivary complex. The dorsal column nuclei project topographically upon the contralateral accessory nuclei with the gracile nucleus sending fibers primarily to the lateral half of the DAO and the cuneate nucleus projecting to rostral cell groups of the MAO. The present results when compared with other olivary connections described by previous studies in a variety of species suggest that regions of the MAO and DAO receiving sensory information from the periphery may lie outside the influence of cerebellar feedback loops.     

Projections from the cerebellar interposed and dorsal column nuclei to the thalamus in the rat: A double anterograde labelling study

It is generally agreed that cerebellar and lemniscal pathways project to largely separate areas of the thalamus and influence different functional areas of the cerebral cortex. Cerebellar afferents arise from neurones in the deep cerebellar nuclei and terminate in the ventral lateral group of thalamic nuclei or the “motor thalamus,” whereas lemniscal afferents arise from the dorsal column nuclei and terminate in the adjacent ventral posterior group of thalamic nuclei or “sensory thalamus.” However, it remains unclear whether or not these pathways converge onto thalamic neurones in the border zone between motor and sensory thalamus. The aim of this study was to compare directly the locations of cerebellar interposed and dorsal column nuclei terminals in the rat thalamus by using a double anterograde labelling technique. Microinjections of dextran-tetramethylrhodamine and dextran-fluorescein were made into the interposed and dorsal column nuclei, and labelled terminals in the thalamus were examined in the same sections. The labelled cerebellar and lemniscal terminals were located in separate areas throughout most of the ventral lateral and ventral posterior lateral nuclei, and there was only a limited region around the rostral border between these nuclei where the two groups of terminals came in close proximity to each other. In this common projection zone, however, cerebellar and lemniscal terminals seldom intermingled, and they mostly occupied separate, discreet areas. The results show that cerebellar and lemniscal fibres do indeed project to the border zone between the sensory and cerebellar thalamic nuclei, but they show practically no overlap in this region and are likely to influence separate thalamic neurones. © 1996 Wiley-Liss, Inc.     

Projections of auditory cortex upon the thalamus and midbrain in the owl monkey.

Two tonotopically organized cortical fields, the primary (AI) and the rostral (R) fields, comprise the core of auditory cortex in the owl monkey. Injections of tritiated proline were made into each of these fields to determine their efferent projections using autoradiographic methods. Both AI and R project to the principal and magnocellular divisions of the medial geniculate body. In addition, R projects to the posterior part of the dorsal division of the medial geniculate. AI sends axons to the dorsomedial region and laminated portion of the central nucleus of the inferior colliculus. Labeling in the central nucleus following AI injections appears as a band of silver grains oriented parallel to isofrequency contours. Axons from R terminate in the dorsomedial region of the central nucleus of the inferior colliculus and in the pericentral and external nuclei of the inferior colliculus. In addition, the rostral field projects to a small area of the medial pulvinar just anterior to the brachium of the superior colliculus.     

Projections of the paraventricular and paratenial nuclei of the dorsal midline thalamus in the rat

The paraventricular (PV) and paratenial (PT) nuclei are prominent cell groups of the midline thalamus. To our knowledge, only a single early report has examined PV projections and no previous study has comprehensively analyzed PT projections. By using the anterograde anatomical tracer, Phaseolus vulgaris leucoagglutinin, and the retrograde tracer, FluoroGold, we examined the efferent projections of PV and PT. We showed that the output of PV is virtually directed to a discrete set of limbic forebrain structures, including 'limbic' regions of the cortex. These include the infralimbic, prelimbic, dorsal agranular insular, and entorhinal cortices, the ventral subiculum of the hippocampus, dorsal tenia tecta, claustrum, lateral septum, dorsal striatum, nucleus accumbens (core and shell), olfactory tubercle, bed nucleus of stria terminalis (BST), medial, central, cortical, and basal nuclei of amygdala, and the suprachiasmatic, arcuate, and dorsomedial nuclei of the hypothalamus. The posterior PV distributes more heavily than the anterior PV to the dorsal striatum and to the central and basal nuclei of amygdala. PT projections significantly overlap with those of PV, with some important differences. PT distributes less heavily than PV to BST and to the amygdala, but much more densely to the medial prefrontal and entorhinal cortices and to the ventral subiculum of hippocampus. As described herein, PV/PT receive a vast array of afferents from the brainstem, hypothalamus, and limbic forebrain, related to arousal and attentive states of the animal, and would appear to channel that information to structures of the limbic forebrain in the selection of appropriate responses to changing environmental conditions. Depending on the specific complement of emotionally associated information reaching PV/PT at any one time, PV/PT would appear positioned, by actions on the limbic forebrain, to direct behavior toward a particular outcome over a range of outcomes.     

Brainstem and spinal projections of the deep cerebellar nuclei in the monkey,with observations on the brainstem projections of the dorsal column nuclei

Miniature end-plate potentials (MEPPs) recorded at the neuromuscular junction were initially reported to be normally distributed and have been attributed to quantal ACh release. This quantum was later correlated with the release of the content of one clear vesicle. This is the ‘classical vesicular hypothesis’. Recent observations of subminiature end-plate potentials (s-MEPPs) and of multimodal distribution of the MEPP amplitudes have led to the formulation of a new 'multivesicular hypothesis'. It attributes the s-MEPP to the release of one vesicle and the MEPP to the simultaneous release of several vesicles at one active zone.The distribution of MEPP intervals, the evaluation of the ACh content of a vesicle and of the ACh necessary to produce a MEPP, estimates of the number of vesicles missing following repeated stimulation, and the freeze fracture studies of the active zone do not permit a definitive rejection of either hypotheses.     

Brainstem and spinal projections of the deep cerebellar nuclei in the monkey, with observations on the brainstem projections of the dorsal column nuclei

The cytoarchitecture of the ventral lateral region of the primate thalamus has been appraised in the frontal, parasagittal and horizontal planes. A morphologically distinct region, possessing a sparse and diffuse distribution of large and small neurons is identified. The region includes several nuclei previously separately named by Olszewski⁴⁵. These are nuclei VPLo, VLc, X, VLps, and some cellular extensions into the VLo nucleus. The whole zone is continuous, and it is shown that no clear separation exists between any of the previously identified sub-nuclei. Connectional grounds are given for suggesting that this region should be considered as a common cerebellar relay nucleus to motor cortex.Morphological criteria for distinguishing the cellsparse nucleus from adjacent nuclei are given. These cytological criteria provide a basis for the experimental analysis of cortical and subcortical connectivity of the ventral lateral thalamic region. Close attention was paid to the border between the VPLo nucleus and the VPLc nucleus. VPLc is separated from VPLo by a clear border, and no transitional zone can be detected in the parasagittal or horizontal planes. Previous ambiguities in the delineation of the VPLo-VPLc border probably stem from analysis in the frontal plane, in which the border is not clear.     

Cortical and reticular influences upon evoked responses in dorsal column nuclei

Cortical influences, conducted in the pyramidal tract, can modify the amplitude and form of the evoked response in dorsal-column nuclei. Both an increase and a decrease in magnitude of responses can be produced by direct cortical stimulation. When the cortex is excited indirectly, through specific thalamocortical connections, only facilitation occurs. This study has explored further ways in which the response can be modified. In the encéphale isolé of the cat, evoked response in dorsal column nuclei can be reduced by stimulation of midbrain tegmentum. When sensorimotor cortex is ablated, this reduction can no longer be obtained; instead, facilitation occurs. Additionally, serially evoked responses in dorsal-column nuclei display a pronounced increase in amplitude after ablation of the sensorimotor cortex. In low pyramidal preparations, the depressor effect continues functioning, showing that this is a direct action through the pyramidal tract. It is concluded that: the cerebral cortex exerts an inhibitory influence upon afferent potentials in the gracile and cuneate nuclei; stimulation of the reticular formation is capable of activating this mechanism; and the reticular formation also has a direct facilitatory effect on these responses in the dorsal-column nuclei.     

Projections from the dorsal column nuclei and the spinal cord to the red nucleus in cat

The projections of the red nucleus (RN) from the dorsal column nuclei (DCN) and the spinal cord have been investigated in cats with the degeneration method. After electrolytic DCN lesions and unilateral cordotomies including the lateral and ventral funiculi, the degeneration was studied in Fink-Heimer stained sections. Contralateral to a DCN lesion terminal degeneration was found along the whole rostrocaudal extent of the red nucleus. In most portions the degeneration was scattered, but dense zones were present, too. Terminal fibers were present in both magnocellular and parvocellular parts. After a gracile lesion the degenerating fibers were restricted to the ventral part of the RN, while the terminal patterns did not differ significantly after cuneate and large DCN lesions. The spinal fibers were found ipsilateral to the cordotomy. Like the DCN fibers, the spinal fibers were present along the whole rostrocaudal extent of the RN and in both magno- and parvocellular zones. Their distribution in the transverse plane was similar, as well. However, the present material was not sufficient to show subtle differences between the DCN and spinal projections, nor to show a possible somatotopical organization of the spinal projection.     

Corticospinal neurons with branching axons to the dorsal column nuclei in the monkey

Previous work in cats has shown that cells of origin of the corticospinal tract give rise to collateral branches to the dorsal column nuclei (DCN). The present experiments were performed in monkeys (Macaca fascicularis) in which 2% fast blue and 2% diamidino yellow were delivered to infiltrate the dorsolateral funiculus at levels between C2 and C6 and the cuneate nucleus on the same side. Retrograde labelling in the cortex allows simultaneous visualization of three classes of neurons: corticospinal tract (CST) neurons, corticocuneate tract (CCT) neurons, and double-labelled neurons. The morphological features and distribution of CST and CCT neurons are similar to those previously reported from investigations based mainly upon the retrograde transport of horseradish peroxidase (HRP). CST neurons occur in layer V in the pre- and postcentral gyri, except for the lateral part (face representation), in the supplementary motor and sensory cortex, and in SII. CCT neurons are present in layer V largely in the postcentral gyrus and in SII. Double-labelled neurons are present wherever CST and CCT neurons are found. Reconstruction and quantitative data from the pericentral cortex show that up to 60% of CCT neurons are double-labelled and are found predominantly in areas 1 and 2, and that their perikarya are in the size range of the larger CCT neurons. Comparison of these results with those obtained previously in cats by using HRP and tritiated, enzymatically inactive HRP (3H-apo-HRP, Rustioni and Hayes: Exp. Brain Res. 43:237-245, 1981) suggests that CST neurons with branching axons to the DCN are considerably more numerous in monkeys than in cats. To determine whether this difference is caused by the different tracers used in the two species. 2% fast blue and 2% diamidino yellow were delivered in cats to infiltrate the dorsolateral funiculus at C2-C3 and the cuneate nucleus on the same side. The results in these cats are remarkably similar to those obtained in the previous study, which used HRP and 3H-apo-HRP: double-labelled neurons occur predominantly in area 3a and constitute 14-16% of the CCT neurons in the pericruciate area. The results bear upon mechanisms of descending control and tuning of performances that characterize the dorsal column-medial lemniscal system, e.g., discrimination of discrete spatiotemporal cues. The species differences may be related to the higher degree of tactile resolution and synchronous control of sensory inflow at the DCN and spinal cord in monkeys relative to cats.     

Inhibition of the dorsal column nuclei

Recordings of electrical changes were made in the dorsal column nuclei in decerebrated cats, in some of which the pericruciate, coronal, and anterior ectosylvian gyri, or parts thereof, were chronically ablated. Single weak test volleys from skin and peripheral nerve or dorsal columns of cord evoked responses slightly above threshold. These were conditioned from either contralateral bulbar pyramid or reticular formation by repetitive volleys. Inhibition of the nuclei of the dorsal columns is obtainable from the contralateral and to a slight extent from the ipsilateral pyramid and from the reticular formation both crossed and uncrossed. The cortical area which yields pyramidal inhibition comprises the pericruciate, coronal, and anterior ectosylvian gyri. The pyramid inhibition is not mediated via the reticular formation above the level of the dorsal column nuclei. It requires at least five volleys and increases in effectiveness up to twenty volleys. It is relatively weak and is easily overcome by large test volleys. It may last for over 200 msec and to a slight degree for several seconds. It is virtually eliminated by small doses of sodium pentobarbital which may reveal a previously hidden facilitation. We regard it as direct inhibition and not as a result of refractoriness.     

Projections of the amygdala to the thalamus in the cynomolgus monkey

The projections of the amygdala to the thalamus in cynomolgus monkeys (Macaca fascicularis) were studied with both anterograde and retrograde axonal tracing techniques. Horseradish peroxidase (HRP) was injected into medial and midline thalamic sites in five animals, and tritiated amino acids were injected into selected amygdaloid regions in a total of 13 hemispheres in ten animals. The findings from the two types of tracer experiments demonstrated the origins, course, and terminal pattern of amygdaloid projections to two thalamic nuclei--medialis dorsalis (MD) and reuniens. Almost all of the amygdaloid nuclei contribute projections to MD, though the greatest proportion arise from the basal group and terminate in discrete, interlocking patches within the medial, magnocellular portion of MD. In addition to this major projection, the central and medial amygdaloid nuclei send a lighter projection to the lateral portion of nucleus reuniens. The amygdalothalamic projections took a variety of routes out of the amygdala before the large majority joined the inferior thalamic peduncle and entered the rostral head of the thalamus where they turned caudally toward their targets. A small number of amygdalothalamic fibers may also run in the stria terminalis.     

Projections of the vestibular and cerebellar nuclei in Rana pipiens

The efferent projections and cytoarchitecture of the vestibulocerebellar region were examined to determine the nuclear boundaries and potential homologies. The anterior portion of the vestibular complex projects to the ipsilateral oculomotor and trochlear nuclei and is the major source of commissural fibers. Neurons in the rostromedial portions of the complex project to the contralateral trochlear nucleus. Large neurons in the ventrolateral portion of the complex give rise to a bilateral vestibulospinal pathway. Medium-sized neurons in the neuropil and small neurons in the central gray giving rise to bilateral projections to the spinal cord and oculomotor nuclei as well as commissural and ipsilateral cerebellar efferents. Projections from the nucleus of the cerebellum reach the contralateral spinal cord and cerebellar nucleus and there is also a bilateral projection to the ventral rhombencephalic and mesencephalic basal plates. The medial portion of the nucleus gives rise to commissural, ipsilateral mesencephalic and contralateral spinal projections. The lateral portion of the nucleus projects to the contralateral ventral mesencephalon. On the whole, the results of this investigation substantiate the division of the anuran vestibular complex in anurans into nuclei which may be homologous to the superior nucleus and nucleus of Deiters in mammals. The case for distinct descending and medial nuclei is less compelling. Further, it appears possible to divide the nucleus of the cerebellum into medial and lateral components whose connectivity is similar to that of reptiles and to a lesser extent mammals.     

Cholecystokinin innervation of rat thalamus, including fibers to ventroposterolateral nucleus from dorsal column nuclei

The distribution of cholecystokinin octapeptide immunoreactive fibers and puncta in the adult rat thalamus was studied using immunocytochemical methods. Small to moderate numbers of immunoreactive fibers were present in the lateral habenular nucleus, ventral lateral geniculate nucleus, zona incerta, parataenial, mediodorsal, medioventral, and submedial nuclei, the rhomboid, paracentral, central lateral and parafascicular nuclei, and in the medial geniculate and dorsal lateral geniculate nuclei. Moderate to large numbers of cholecystokinin (CCK)-positive fibers were present in the paraventricular nuclei, the reticular nucleus, the anteroventral, anteromedial, and central medial nuclei, and in the rostral extension of the internal medullary lamina between the parataential and anteroventral nuclei. Dense concentrations of immunoreactive fibers were also found in a principal sensory relay nucleus, the ventroposterolateral nucleus (VPL), of the ventrobasal complex. The number of CCK-positive fibers in VPL showed a marked unilateral decrease in rats which had received lesions of the contralateral gracile and cuneate nuclei. The results of this study demonstrate that CCK-immunoreactive fibers and puncta are widely distributed in the rat thalamus, and that the source of these fibers in VPL is probably the dorsal column nuclei.     

Transneuronal changes of the inhibitory circuitry in the macaque somatosensory thalamus following lesions of the dorsal column nuclei

The inhibitory circuitry of the ventroposterolateral nucleus (VPL) of the macaque somatosensory thalamus was analyzed in normal animals and in those surviving for a few days or several weeks following a unilateral lesion of the cuneate nucleus, the source of medial lemniscal (ML) axons carrying information from the contralateral upper extremity. Inhibitory synaptic terminals in the VPL were defined as those that contain flattened or pleomorphic synaptic vesicles and that can be shown to be immunoreactive for γ-aminobutyric acid (GABA). There are two types of these profiles: F axon terminals that arise from neurons of the thalamic reticular nucleus, and perhaps from VPL local circuit neurons (LCNs); and the dendritic appendages of LCNs that form presynaptic dendrites (PSDs). ML terminals normally have extensive synaptic interactions with PSDs but not with F axon terminals. Electron microscopic analyses revealed that cuneatus lesions resulted in a rapid loss of ML terminals and a statistically significant reduction in both F and PSD synaptic profiles. Confocal scanning microscopy also demonstrated a profound loss of GABA immunoreactivity in the deafferented VPL. These changes persisted for more than 20 weeks, without any evidence of reactive synaptogenesis of surviving sensory afferents or of inhibitory synapses. The changes in GABA circuitry are transneuronal, and the possible mechanisms that may underlie them are discussed. It is suggested that the altered GABAergic circuitry of the VPL in the monkey may serve as a model for understanding changes in somatic sensation in the human following peripheral or central deafferentation. © 1996 Wiley-Liss, Inc.     

Projection of dorsal column nuclei and spinal cord to brainstem and thalamus in the tree shrew, Tupaia glis

The aim of this study was to compare the projections of the dorsal column nuclei and spinal pathways to the brainstem and thalamus in Tupaia glis. Animals with unilateral lesions in the dorsal column nuclei or with lateral hemisections were perfused after 5 to 14 days survival time and sections were treated with Nauta or Fink/Heimer silver impregnation methods. The findings indicate that efferent fibers of dorsal column nuclei terminate not only in the thalamus but also in the dorsal accessory nucleus of the inferior olive and bilaterally in the external nucleus of the inferior colliculus. Some fibers terminate in periaqueductal gray and a few in pontine nuclei. In the diencephalon, efferents of the dorsal column nuclei were found to terminate in the posterior group (PO), ventroposterior nucleus (VP) and zona incerta. Spinal efferents were traced to the medial and dorsal accessory nuclei of the inferior olive, medullary and mesencephalic reticular formation, facial and vestibular nuclei, cuneiform nucleus, locus caeruleus, parabrachial nuclei and periaqueductal gray, and also to the external nucleus of the inferior colliculus. Evidence was found of more limited additional spinal projections to PO intralaminar nuclei and VP. The results of this study indicate that the dorsal column system, generally considered to be a phylogenetically new direct pathway to the thalamus, contains other components comparable to some of the spinal efferent connections with the brainstem. Moreover, even in this intermediate form, whose exact taxonomic position is unsettled, the dorsal column-medial lemniscus system to the thalamus appears to be of greater volume than the anterolateral spinothalamic connection.