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GABAergic projection from the ventral tegmental area and substantia nigra to the periaqueductal gray region and the dorsal raphe nucleus.

Previous studies have shown that neurons in the ventral tegmental area (VTA) and substantia nigra (SN) project to the ventrolateral periaqueductal gray (PAGvl) and dorsal raphe nucleus (DR). Research has also shown that stimulation of neurons in the VTA/SN elicits cardiovascular depressor responses that are mediated by a projection to the PAGvl/DR. Anatomic and physiological experiments were done in the present study to determine the neurochemical identity of the VTA/SN projection to the PAGvl/DR. Experiments were done to characterize the origin and chemical nature of this projection by combining cholera toxin B tracing with immunofluorescence for the 67K isoform of glutamic acid decarboxylase (GAD) and tyrosine hydroxylase. The PAGvl/DR region was found to receive a substantial input from neurons in the VTA, SN, and deep mesencephalic nucleus. The DR was preferentially innervated by neurons in the VTA, whereas the PAGvl was preferentially innervated by neurons in the SN. A proportion of neurons in the VTA and the reticular portion of the SN found to project to the PAGvl/DR were GAD positive. In addition, experiments were done in urethane-anesthetized rats to determine whether injections of a gamma-aminobutyric acid (GABA) antagonist in the region of the PAGvl/DR attenuated the cardiovascular depressor responses produced by glutamate stimulation of the VTA/SN. Injections of the GABA-blocking agent picrotoxin (2.5 nmol, 500 nl) into the PAGvl/DR eliminated the cardiovascular responses from stimulation of the VTA/SN (0.01 M, 50 nl). The results of the present investigation provide evidence for a GABAergic projection from the VTA/SN to the PAGvl/DR. This projection may be an important regulator of the PAGvl/DR, an area of the midbrain involved in the production of behavioral and physiological responses to pain and stress.

Animals↗

Neuropeptide expression in rat paraventricular hypothalamic neurons that project to the spinal cord.

The paraventricular hypothalamic nucleus (PVH) exerts many of its regulatory functions through projections to spinal cord neurons that control autonomic and sensory functions. By using in situ hybridization histochemistry in combination with retrograde tract tracing, we analyzed the peptide expression among neurons in the rat PVH that send axons to the spinal cord. Projection neurons were labeled by immunohistochemical detection of retrogradely transported cholera toxin subunit B, and radiolabeled long riboprobes were used to identify neurons containing dynorphin, enkephalin, or oxytocin mRNA. Of the spinally projecting neurons in the PVH, approximately 40% expressed dynorphin mRNA, 40% expressed oxytocin mRNA, and 20% expressed enkephalin mRNA. Taken together with our previous findings on the distribution of vasopressin-expressing neurons in the PVH (Hallbeck and Blomqvist [1999] J. Comp. Neurol. 411:201-211), the results demonstrated that the different PVH subdivisions display distinct peptide expression patterns among the spinal cord-projecting neurons. Thus, the lateral parvocellular subdivision contained large numbers of spinal cord-projecting neurons that express any of the four investigated peptides, whereas the ventral part of the medial parvocellular subdivision displayed a strong preponderance for dynorphin- and vasopressin-expressing cells. The dorsal parvocellular subdivision almost exclusively contained dynorphin- and oxytocin-expressing spinal cord-projecting neurons. This parcellation of the peptide-expressing neurons suggested a functional diversity among the spinal cord-projecting subdivisions of the PVH that provide an anatomic basis for its various and distinct influences on autonomic and sensory processing at the spinal level.

Animals↗

Neuromodulator content of hamster intergeniculate leaflet neurons and their projection to the suprachiasmatic nucleus or visual midbrain.

The intergeniculate leaflet (IGL) of the lateral geniculate complex has widespread, bilateral, and reciprocal connections with nuclei in the subcortical visual shell. Its function is poorly understood with respect to its role in visual processing. The most well-known IGL projection, and the only one with a clear function, is the geniculohypothalamic tract (GHT) that terminates in the suprachiasmatic nucleus (SCN), site of the primary circadian clock. The hamster GHT is derived, in part, from IGL neurons containing neuropeptide Y and enkephalin. IGL neurons containing these peptides also project to the pretectal region. The present studies used a combination of immunohistochemical, lesion, and retrograde tracing techniques to study neuron types in the IGL and their projections to hamster SCN and pretectum. Two additional neuromodulators, gamma-aminobutyric acid (GABA) and neurotensin, are shown to be present in IGL neurons. The GABA- and neurotensin-immunoreactive neurons project to the SCN with terminal field patterns very similar to those for neuropeptide Y and enkephalin. IGL neurons of all four types also send projections to the pretectum, but rarely do individual cells project to both the SCN and the pretectum. Nearly all neurotensin is colocalized with neuropeptide Y in IGL neurons, although about half of the neuropeptide Y cells do not contain neurotensin. Otherwise, the extent to which the four neuromodulators are colocalized varies from 6% to 54%. Nearly every SCN neuron appears to contain GABA. In the IGL, the majority of cells studied are not identifiable by GABA immunoreactivity. Putative functions of the various neuromodulator projections from the IGL to pretectum or SCN are discussed.

Animals↗

Identification of NPY-induced c-Fos expression in hypothalamic neurones projecting to the dorsal vagal complex and the lower thoracic spinal cord.

Neuropeptide Y exerts profound effects on body weight and glucose homeostasis. We have investigated the effect of centrally administered neuropeptide Y on the activity of descending neurones of the hypothalamic paraventricular nucleus by combining retrograde tract tracing with c-Fos immunocytochemistry. Male rats were injected with True Blue into the dorsal vagal complex and with FluoroGold into the intermediolateral column of the lower thoracic spinal cord. One week after the last surgical procedure, animals were injected centrally with an orexigenic dose of neuropeptide Y (5 microg) and sacrificed 60 to 240 minutes following this injection. Temporal analysis of NPY-induced c-Fos expression showed a peak at 90 minutes, which was nearly returned to basal levels between 120 and 240 minutes. Expression of c-Fos was prominent in several of the subnuclei of the paraventricular nucleus and in the adjacent perifornical nucleus. Neurones projecting to the spinal cord were prominent in the dorsal, lateral, and ventral portion of the medial parvicellular subnuclei of the PVN. About 15% of IML projecting neurones of the medial parvicellular subnucleus were Fos-positive, whereas less than 5% of IML projecting neurones from other subnuclei were Fos-positive. Hardly any PVN neurones projecting to the dorsal vagal complex were concomitantly Fos-positive. A considerably larger (>10%) proportion of perifornical neurones projecting to the nucleus of the solitary tract were c-Fos-immunopositive. In conclusion, NPY induces c-Fos in paraventricular neurones projecting to intermediolateral column of the spinal cord and in neurones of the perifornical nucleus projecting to the dorsal vagal complex.

Animals↗

Crossed and uncrossed projections to the cat sacrocaudal spinal cord: III. Axons expressing calcitonin gene-related peptide immunoreactivity.

We have investigated the projection patterns of peptidergic small-diameter primary afferent fibers to the cat sacrocaudal spinal cord, a region associated with midline structures of the lower urogenital system and of the tail. Calcitonin gene-related peptide (CGRP)-immunoreactive (CGRP-IR) primary afferent fibers were observed within the superficial laminae, rostrally as the typical inverted U-shaped band that capped the separate dorsal horns (S1 to rostral S2) and caudally as a broad band that spanned the entire mediolateral extent of the fused dorsal horns (caudal S2 and caudal). Within the dorsal gray commissure, labeling was seen as a periodic vertical, midline band. CGRP-IR labeling was prevalent in an extensive mediolateral distribution at the base of the dorsal horn, originating from both lateral and medial collateral bundles that extend from the superficial dorsal horn. Some bundles, in part traveling within the dorsal commissure, conspicuously crossed the midline. In addition to the robust projection to the superficial dorsal horn, there was a more extensive distribution of CGRP-IR fibers within the deeper portions of the cat sacrocaudal dorsal horn than has been reported for other regions of the cat spinal cord. Presumably, these deep projections convey visceral information to projection or segmental neurons at the neck of the dorsal horn and in the region of the central canal. This deep distribution overlaps the reported projections of the pelvic and pudendal nerves. In addition, the contralateral projections of CGRP-IR fibers may form an anatomical substrate of the bilateral receptive fields for selective dorsal horn neurons. The density and variety of CGRP-IR projection patterns is a reflection of the functional attributes of the innervated structures.

Animals↗

Perirhinal and parahippocampal cortices of the macaque monkey: Intrinsic projections and interconnections.

We investigated the topographic and laminar organization of the intrinsic projections and interconnections of the macaque monkey perirhinal and parahippocampal cortices. Discrete anterograde tracer injections placed at various rostrocaudal and mediolateral levels in these cortices revealed extensive associational connections both within and between the perirhinal and parahippocampal cortices. Areas 35, 36rm, 36rl, 36cm, and 36cl are highly interconnected, whereas area 36d (encompassing the dorsal portion of the medial temporal pole) shares only modest connections with the rest of the perirhinal cortex. Areas TH, TFm, and TFl of the parahippocampal cortex also share an extensive network of associational connections that tend to be heaviest within a given subdivision. Area 36c of the perirhinal cortex is the main interface between the perirhinal and parahippocampal cortices. Its heaviest connections are with area 36r and the anterior aspect of area TF. The laminar organization of all these connections is typical of associational projections. Anterograde tracer experiments revealed that these projections are distributed through both deep and superficial layers, although heavier projections are directed toward the superficial layers. Results of retrograde tracer experiments suggested that the projections from caudal areas (36c or TF) to area 36r are of the feedforward type, whereas the projections from areas 36r and 36c to area TF are of the feedback type. These findings suggest that the perirhinal cortex is at a higher level than the parahippocampal cortex in the hierarchy of associational cortices. We discuss the functional implications of the organization of these extensive networks of intrinsic, associational projections.

Animals↗

Amygdalostriatal projections in reptiles: a tract-tracing study in the lizard Podarcis hispanica.

Whereas the lacertilian anterior dorsal ventricular ridge contains unimodal sensory areas, its posterior part (PDVR) is an associative center that projects to the hypothalamus, thus being comparable to the amygdaloid formation. To further understand the organization of the reptilian cerebral hemispheres, we have used anterograde and retrograde tracing techniques to study the projections from the PDVR and adjoining areas (dorsolateral amygdala, DLA; deep lateral cortex, dLC; nucleus sphericus, NS) to the striatum in the lizard Podarcis hispanica. This information is complemented with a detailed description of the organization of the basal telencephalon of Podarcis. The caudal aspect of the dorsal ventricular ridge projects nontopographically mainly (but not exclusively) to the ventral striatum. The NS projects bilaterally (with strong ipsilateral dominance) to the nucleus accumbens, thus recalling the posteromedial cortical amygdala of mammals. The PDVR (especially its lateral aspect) and the dLC project massively to a continuum of structures connecting the striatoamygdaloid transition area (SAT) and the nucleus accumbens (rostrally), the projection arising from the dLC being probably bilateral. Finally, the DLA projects massively and bilaterally to both the ventral and dorsal striatum, including the SAT. Our findings lend further support to the view that the PDVR and neighboring structures constitute the reptilian basolateral amygdala and indicate that an emotional brain was already present in the ancestral amniote. These results are important to understand the comparative significance of the caudal aspect of the amniote cerebral hemispheres, and specifically challenge current views on the nature of the avian caudal neostriatum.

Amygdala↗

Octavolateral projections and organization in the medulla of a teleost fish, the sleeper goby (Dormitator latifrons).

This study is the first to employ simultaneous labeling with different colored fluorescent dyes and confocal microscopy to investigate the central projections of the octavolateral nerves in any fish. Three-dimensional reconstructions of the hindbrain octavolateral nuclei were made and overlap of octavolateral projections was assessed in a teleost, the sleeper goby (Dormitator latifrons). The octavolateral nerves, which innervate the otolithic organs, semicircular canals, and lateral lines, project to seven hindbrain nuclei in diverse, complex patterns. The medulla is generally organized with auditory regions dorsal to vestibular regions. The intermediate subdivision of the descending octaval nucleus (DON) receives interdigitating projections from the otolithic organs, and the dorsomedial DON likely integrates multiple auditory inputs. Afferents from the three otolithic organs (the utricle, saccule, and lagena) project to the intermediate DON in approximately equal proportion, supporting physiological evidence that suggests auditory roles for all three otolithic organs in the sleeper goby. The anterior octaval nucleus receives partially segregated inputs from the octavolateral organs. The dorsal division of the magnocellular octaval nucleus (MgON) receives highly overlapping otolithic organ and semicircular canal input, and we propose that this region is a major octaval integration center. Regions in the ventral medulla (the tangential octaval nucleus, ventral DON, and ventral MgON) receive mainly utricular and semicircular canal inputs, suggesting vestibular roles. Each semicircular canal nerve projects to distinct regions of the hindbrain, with little overlap in most octaval nuclei. Efferent neurons receive bilateral input and project unilaterally to the octavolateral organs.

Afferent Pathways↗

Thalamic innervation of the direct and indirect basal ganglia pathways in the rat: Ipsi- and contralateral projections.

The present study describes the thalamic innervation coming from the rat parafascicular nucleus (PF) onto striatal and subthalamic efferent neurons projecting either to the globus pallidus (GP) or to the substantia nigra pars reticulata (SNr) by using a protocol for multiple neuroanatomical tracing. Both striatofugal neurons targeting the ipsilateral SNr (direct pathway) as well as striatal efferent neurons projecting to the ipsilateral GP (indirect pathway) were located within the terminal fields of the thalamostriatal afferents. In the subthalamic nucleus (STN), both neurons projecting to ipsilateral GP as well as neurons projecting to ipsilateral SNr also appear to receive thalamic afferents. Although the projections linking the caudal intralaminar nuclei with the ipsilateral striatum and STN are far more prominent, we also noticed that thalamic axons could gain access to the contralateral STN. Furthermore, a small number of STN neurons were seen to project to both the contralateral GP and PF nuclei. These ipsi- and contralateral projections enable the caudal intralaminar nuclei to modulate the activity of both the direct and the indirect pathway.

Animals↗

Descending projections from the auditory cortex to the inferior colliculus in the gerbil, Meriones unguiculatus.

Corticofugal projections to the auditory midbrain, the inferior colliculus (IC), influence the way in which specific sets of IC neurons process acoustic signals. We used retrograde tracer (Fluorogold, Fluororuby, microbeads) injections in the IC to study the morphology and location of cortico-collicular projecting neurons and anterograde tracer (dextran biotin) injections in auditory cortical fields to describe the distribution of terminals in the IC. Nissl staining, cytochrome oxidase activity, and neurofilament SMI32 immunostaining were used to delimit the different auditory areas. We defined a primary or "core" auditory cortex and a secondary "caudal" auditory area containing layer V pyramidal neurons that project to the IC. These projections target the central nucleus of the IC (CNIC) ipsilaterally and the IC cortices bilaterally, with the ipsilateral component predominant. Other secondary auditory areas, dorsal and ventral to the core, do not directly participate in this projection. The ventral secondary cortex targets midbrain periaqueductal gray. The projection from the core cortex originates from two classes of layer V pyramidal cells. Cells presenting a tufted apical dendrite in layer I have dense terminal fields in the IC cortices. Pyramids lacking layer I dendritic tufts target the CNIC in a less dense but tonotopic manner. The caudal cortex projection originates from smaller layer V pyramids and targets the IC cortices with dense terminal fields. Descending auditory inputs from the core and caudal areas converge in the dorsal and external cortices of the IC. Descending connections to the gerbil IC form a segregated system in which multiple descending channels originating from different neuronal subpopulations may modulate specific aspects of ascending auditory information.

Animals↗

Descending projections of the hamster intergeniculate leaflet: relationship to the sleep/arousal and visuomotor systems.

The intergeniculate leaflet (IGL), homolog of the primate pregeniculate nucleus, modulates circadian rhythms. However, its extensive anatomical connections suggest that it may regulate other systems, particularly those for visuomotor function and sleep/arousal. Here, descending IGL-efferent pathways are identified with the anterograde tracer, Phaseolus vulgaris leucoagglutinin, with projections to over 50 brain stem nuclei. Projections of the ventral lateral geniculate are similar, but more limited. Many of the nuclei with IGL afferents contribute to circuitry governing visuomotor function. These include the oculomotor, trochlear, anterior pretectal, Edinger-Westphal, and the terminal nuclei; all layers of the superior colliculus, interstitial nucleus of the medial longitudinal fasciculus, supraoculomotor periaqueductal gray, nucleus of the optic tract, the inferior olive, and raphe interpositus. Other target nuclei are known to be involved in the regulation of sleep, including the lateral dorsal and pedunculopontine tegmentum. The dorsal raphe also receives projections from the IGL and may contribute to both sleep/arousal and visuomotor function. However, the locus coeruleus and medial vestibular nucleus, which contribute to sleep and eye movement regulation and which send projections to the IGL, do not receive reciprocal projections from it. The potential involvement of the IGL with the sleep/arousal system is further buttressed by existing evidence showing IGL-efferent projections to the ventrolateral preoptic area, dorsomedial, and medial tuberal hypothalamus. In addition, the great majority of all regions receiving IGL projections also receive input from the orexin/hypocretin system, suggesting that this system contributes not only to the regulation of sleep, but to eye movement control as well.

Afferent Pathways↗

Ephrin-A2 and -A5 influence patterning of normal and novel retinal projections to the thalamus: conserved mapping mechanisms in visual and auditory thalamic targets.

Sensory axons are targeted to modality-specific nuclei in the thalamus. Retinal ganglion cell axons project retinotopically to their principal thalamic target, the dorsal lateral geniculate nucleus (LGd), in a pattern likely dictated by the expression of molecular gradients in the LGd. Deafferenting the auditory thalamus induces retinal axons to innervate the medial geniculate nucleus (MGN). These retino-MGN projections also show retinotopic organization. Here we show that ephrin-A2 and -A5, which are expressed in similar gradients in the MGN and LGd, can be used to pattern novel retinal projections in the MGN. As in the LGd, retinal axons from each eye terminate in discrete eye-specific zones in the MGN of rewired wild-type and ephrin-A2/A5 knockout mice. However, ipsilateral eye axons, which arise from retinal regions of high EphA5 receptor expression and represent central visual field, terminate in markedly different ways in the two mice. In rewired wild-type mice, ipsilateral axons specifically avoid areas of high ephrin expression in the MGN. In rewired ephrin knockout mice, ipsilateral projections shift in location and spread more broadly, leading to an expanded representation of the ipsilateral eye in the MGN. Similarly, ipsilateral projections to the LGd in ephrin knockout mice are shifted and are more widespread than in the LGd of wild-type mice. In the MGN, as in the LGd, terminations from the two eyes show little overlap even in the knockout mice, suggesting that local interocular segregation occurs regardless of other patterning determinants. Our data demonstrate that graded topographic labels, such as the ephrins, can serve to shape multiple related aspects of afferent patterning, including topographic mapping and the extent and spread of eye-specific projections. Furthermore, when mapping labels and other cues are expressed in multiple target zones, novel projections are patterned according to rules that operate in their canonical targets.

Animals↗

Movement suppression during anesthesia: neural projections from the mesopontine tegmentum to areas involved in motor control.

Microinjection of pentobarbital and GABA(A)-receptor agonists into a brainstem region we have called the mesopontine tegmental anesthesia area (MPTA; Devor and Zalkind [2001] Pain 94:101-112) induces a general anesthesia-like state. As in systemic general anesthesia, rats show loss of the righting reflex, atonia, nonresponsiveness to noxious stimuli, and apparent loss of consciousness. GABA(A) agonist anesthetics acting on the MPTA might suppress movement by engaging endogenous motor regulatory systems previously identified in research on decerebrate rigidity and REM sleep atonia. Anterograde and retrograde tracing revealed that the MPTA has multiple descending projections to pontine and medullary areas known to be associated with motor control and atonia. Prominent among these are the dorsal pontine reticular formation and components of the rostral ventromedial medulla (RVM). The MPTA also has direct projections to the intermediate gray matter and ventral horn of the spinal cord via the lateral and anterior funiculi. These projections show a rostrocaudal topography: neurons in the rostral MPTA project to the RVM, but only minimally to the spinal cord, while those in the caudal MPTA project to both targets. Finally, the MPTA has ascending projections to motor control areas including the substantia nigra, subthalamic nucleus, and the caudate-putamen. Projections are bilateral with an ipsilateral predominance. We propose that GABA(A) agonist anesthetics induce immobility at least in part by acting on these endogenous motor control pathways via the MPTA. Analysis of MPTA connectivity has the potential for furthering our understanding of the neural circuitry responsible for the various functional components of general anesthesia.

Anesthetics↗

Distribution within the barn owl's inferior colliculus of neurons projecting to the optic tectum and thalamus.

Behavioral studies in barn owls indicate that both the optic tectum (OT) and the auditory arcopallium (AAr) mediate sound localization through the presence of neurons that respond only when sound comes from a circumscribed direction in space. The early stages of the computations leading to these so-called space-specific neurons are shared in a common brainstem pathway, which then splits at the level of the inferior colliculus (IC) such that the last computational stage is thought to be duplicated. The study presented here addresses whether the space-specific neurons in OT and AAr are indeed partially independent of each other by using anatomical methods more precise than those used in previous studies. Specifically, projection neurons in IC were retrogradely labelled with injections of fluorescein- and rhodamine-conjugated dextran amines into OT and nucleus ovoidalis (OV), the thalamic nucleus leading to AAr. By labelling the OT-projecting and OV-projecting neurons in the same owl, it was confirmed that neurons in IC project to either OV or OT but not both. However, although a segregation was generally observed between the medially positioned OV-projecting neurons and the laterally positioned OT-projecting neurons, there was also a slight overlap between the two populations. Moreover, electrolytic lesions demarcating physiological tuning properties indicate that many OV-projecting neurons are within the area containing space-specific neurons. These results highlight the need for more detailed studies elucidating the microcircuitry and corresponding physiology of IC, such as have been done in the cortices of the mammalian cerebellum and cerebrum.

Animals↗

Ontogeny of the projections from the anteroventral periventricular nucleus of the hypothalamus in the female rat.

Neurons in the anteroventral periventricular nucleus of the hypothalamus (AVPV) mediate a variety of autonomic functions. In adults they primarily innervate neuroendocrine nuclei in the periventricular zone of the hypothalamus, including the paraventricular and arcuate nuclei (PVH, ARH). Ascending projections from the AVPV also provide inputs to the ventrolateral septum (LSv) and the principal division of the bed nuclei of the stria terminalis (BSTp). Consistent with a role in regulating preovulatory luteinizing hormone secretion, rostral projections from the AVPV contact gonadotropin-releasing hormone (GnRH) neurons surrounding the vascular organ of the lamina terminalis (OVLT). To study the development of these pathways, we placed implants of the lipophilic tracers DiI and CMDiI into the AVPV of female rats ranging in age from embryonic day 19 (E19) through adulthood. The earliest projections targeted a population of GnRH neurons, with apparent contacts from labeled fibers observed as early as E19. These connections appeared to be fully developed before birth, as similar numbers of appositions from AVPV projections onto the GnRH-immunoreactive cells were observed at all ages examined. Caudal projections were delayed relative to projections to the OVLT. Labeled AVPV fibers reached the PVH during the first postnatal week, and fibers targeting the BSTp and LSv were not observed until the second and third postnatal weeks, respectively. Labeled AVPV fibers were not seen in the ARH of animals at any age. Our results demonstrate that projections from the AVPV develop with both spatial and temporal specificity, innervating each target with a unique developmental profile.

Aging↗

The olivocerebellar projection in the cat studied with the method of retrograde axonal transport of horseradish peroxidase.

The distribution of labeled cells in the inferior olive of the cat has been mapped following injections of small amounts of horseradish perosidase in the paramedian lobule of the cerebellum. The distribution of labeled cells was plotted in drawings of approximately serial transverse sections. The findings in each case were transferred to a standard diagram of the olive to facilitate comparison of cases. Previous studies of the distribution of retrograde cell loss in the inferior olive following cerebellar lesions (Brodal, '40b) showed that fibers ending in the paramedian lobule come from the caudal part of the ventral lamella of the principla olive. This was confirmed with the peroxidase method, but in addition three other separate and well circumscribed area of the olive showed labeling: one in the dorsal accessory olive, another in the rostral part of the medial accessory olive, a third in the caudal part of the dorsal lamella of the principal olive (fig. 7). There is some degree of topical arrangement within the projection of each of these olivary areas to the paramedian lobule. It is particularly striking that the projection areas of the caudal one-third of the lobule are different from and overlap only little with those of the orstral two-thirds. On account of diffusion of the injected perosidase solution in the folia it could not be decided whether the different olivary areas project to particular longitudinal zones in the paramedian lobule. The main findings can be correlated with the physiological observations of Armstrong et al. ('74). Some of the "paramedian" olivary areas are labeled also following peroxidase injections in other cerebellar parts, among them the nuclei interpositus anterior and posterior. The findings are compatible with the notion that olivocerebellar fibers branch to supply more than one cerebellar region. It is confirmed that the olivocerebellar projection, including that of the nuclei, is almost completely crossed. In the discussion it is emphasized that afferents from several sources converge on all four olivary regions projecting onto the paramedian lobule. The olivocerebellar projection obviously allows for divergence as well as convergence of impulses from the olive to the cerebellum. For further insight into the anatomical organization of the inferior olive, the entire olivocerebellar projection has to be mapped with the peroxidase methods, and further studies of the afferents to the olive are needed. In such studies, as well as in physiological ones, it is essential that findings are described with meticulous reference to the topography of the olivary subdivisions.

Animals↗

Nigrothalamic projections in the monkey demonstrated by autoradiographic technics.

In spite of repeated demonstrations by degeneration technics, nigrothalamic fibers have been regarded with some skepticism. Attempts were made to trace nigral efferent projections in the monkey by autoradiographic technics. Tritiated amino acids (L-leucine, L-lysine and L-proline), injected into portions of the substantia nigra (SN), labeled cells in four regions, designated as, (1) rostrolateral, (2) caudolateral, (3) rostromedial and (4) central. Rostrolateral nigral neurons transported radioactive label preferentially and abundantly to thalamic nuclei; localized isotope was found in parts of three thalamic nuclei, the medial part of the ventral lateral nucleus (VLm), the magnocellular part of the ventral anterior nucleus (VAmc), and the paralaminar part of the dorsomedial nucleus (DMpl)9 Lateral neurons in the caudal half of the SN transmitted radioactive label to the same thalamic nuclei as rostrolateral nigral neuron. Isotope transported to portions of the striatum was modest and localized. Radioactive label taken up by large cells in the caudal third of the SN was transported to portions of the striatum, but not to thalamic nuclei. Labeled nigral neurons in the medial two-thirds of the rostral half of the SN, and in the middle third of the central part of the SN, transported the label mainly to parts of the caudate nucleus and putamen. In these animals modest radioactive label was seen in VLm and VAmc, but not in other thalamic nuclei. There was no evidence that nigral neurons project to the subthalamic nucleus. No radioactive transport from nigral neurons was detected in the superior colliculus, the midbrain tegmentum, or the red nucleus, and none was transported to more caudal brain stem nuclei. Nigrothalamic fibers arise particularly from cells in rostral and lateral parts of the substantia nigra. While some cells in other parts of the nigra project to thalamic nuclei, these appear scattered and less numerous. Large cells in caudal parts of the SN do not project to thalamic nuclei. These observations confirm nigrothalamic projections to VLm and VAmc, and identify a new nigral projection to part of the dorsomedial nucleus of the thalamus (DMpl). No nigral efferent fibers project to any of the intralaminar thalamic nuclei.

Animals↗

Retinal projections in larval, transforming and adult sea lamprey, Petromyzon marinus.

Unilateral enucleations were performed on larval, transforming and adult sea lampreys. Following 5 to 11 days survival, the animals were sacrificed and the brains were processed using a modified Fink-Heimer technique. In larvae, contralateral optic projections were found to the posterior one-third of the dorsal thalamus, the pretectum, and the optic tectum. No ipsilateral projections were present in the larvae. In enucleated transforming and adult lampreys, degenerating axons were observed in the optic chiasm and bilaterally in the optic tracts. Retinal efferents projected bilaterally to a lateral neuropil region ("tractus opticus") in the posterior one-half of the dorsal thalamus. Contralaterally, a conspicuous dorsomedial cell group (lateral geniculate nucleus) also received a projection. Contralateral projections to the superficial layers of the pretectum and optic tectum were observed. Ipsilateral retinal projections to the pretectum and optic tectum in transforming and adult lampreys were restricted to a small zone at the ventrolateral margins of the pretectum and tectum. The changes in distribution of retinofugal projections during transformation appear to be occurring at the same time that the eye differentiates into its adult form.

Animals↗