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Serotonin neurons of the midbrain raphe: ascending projections.

The ascending projections of serotonin neurons of the midbrain raphe were analyzed in the rat using the autoradiographic tracing method. Axons of raphe serotonin neurons ascend in the ventral tegmental area and enter the medial forebrain bundle. A number of fibers leave the major group to ascend along the fasciculus retroflexus. Some fibers enter the habenula but the majority turn rostrally in the internal medullary lamina of the thalamus to innervate dorsal thalamus. Two additional large projections leave the medial forebrain bundle in the hypothalamus; the ansa peduncularis-ventral amygdaloid bundle system turns laterally through the internal capsule into the striatal complex, amygdala and the external capsule to reach lateral and posterior cortex, and another system of fibers turns medially to innervate medial hypothalamus and median eminence and form a contrelateral projection via the supraoptic commissures. Rostrally the major group in the medial forebrain bundle divides into several components: fibers entering the stria medullaris to terminate in thalamus; fibers entering the stria terminalis to terminate in the amygdala; fibers traversing the fornix to the hippocampus; fibers running through septum to enter the cingulum and terminate in dorsal and medial cortex and in hippocampus; fibers entering the external capsule to innervate rostral and lateral cortex; and fibers continuing forward in the medial olfactory stria to terminate in the anterior olfactory nucleus and olfactory bulb.

5,6-Dihydroxytryptamine↗

The hypothalamic magnocellular system of the rhesus monkey: an immunocytochemical study.

The hypothalamic magnocellular system of the adult female rhesus monkey is studied here, using immunoperoxidase technique and antisera to estrogen stimulated neurophysin (ESN), nicotine stimulated neurophysin (NSN), oxytocin (OT) and vasopressin (VP). These observations confirm and enlarge previous descriptions by others using Gomori techniques. It is apparent from this study that the magnocellular system spreads through a broader area than is generally accepted. A group of cells ventral to the head of the caudate nucleus and medial to the internal capsule is described. The general orientation of the nuclei and their tracts can only be appreciated when coronal, horizontal and sagittal sections are compared. Our observations suggest that the supraoptic nucleus is made up of a single group of cells that straddles the optic pathways, and is not divided in three segments, as it is generally described. It is also shown that the rostral extensions of the paraventricular and supraoptic nuclei merge above the optic chiasm. Cells containing ESN/OT and NSN/VP are evenly dispersed in the paraventricular nucleus but a topographical arrangement is present in the supraoptic nucleus. The magnocellular nuclei project to the organum vasculosum of the lamina terminalis, zona externa of the median eminence and pars nervosa of the pituitary gland. Reactive fibers were also seen within islets of cells from the pars intermedia located inside the pars nervosa. A globular structure containing small blood vessels surrounded by positive fibers was noticed protruding into the floor of the third ventricle, at the level of the median eminence.

Animals↗

Efferent projections of the deep mesencephalic nucleus (pars lateralis) in the rat.

The projections of the lateral part of the deep mesencephalic nucleus (DMN) were traced by autoradiography and retrograde horseradish peroxidase (HRP) techniques. At the level of the DMN, projections from its lateral part crossed the midline and terminated in the medial and lateral part of the contralateral DMN. Furthermore, two labeled tracts passed rostrally from the lateral part of the DMN. One tract coursed dorsolaterally from the lateral DMN to terminate in the ipsilateral lateral thalamic nucleus. The second tract coursed ventrally and rostrally over the substantia nigra toward the ipsilateral zona incerta. At the caudal part of the zona incerta these fibers divided into two bundles. One bundle coursed superiorly to terminate bilaterally in the mediodorsal nucleus of the thalamus. The second bundle of fibers passed anteriorly to enter the ipsilateral zona incerta. Some of these fibers terminated upon neurons of the zona incerta and the ventromedial part of the subthalamic nucleus. The remaining fibers within the zona incerta coursed anteriorly to enter the internal capsule. These fibers terminated in the entopeduncular nucleus and medial part of the globus pallidus. These findings indicate that the lateral part of the DMN is likely to be involved in the ascending activating system of the reticular formation by connections with thalamic nuclei. Furthermore, the lateral part of the DMN may play a part in suprasegmental motor control via connections with rostral brain stem motor centers.

Animals↗

Autoradiographic tracing of developing subcortical projections of the occipital region in fetal rabbits.

Thirty rabbit embryos and two neonates (E18-P1) received micropipette injections of 3H-Leucine into the occipital region of one hemisphere and were killed after 0.5--5 hours. Incorporated tracer was demonstrated by autoradiography of serial sections of the brains. The first axons were seen in the intermediate zone of the developing cerebral cortex, on day E20, and by day E22 they reached the internal capsule. The entire cortico-peduncular bundle and a short branch of the superficial (thalamic) bundle were labeled on day E24. On day E25, additional branches directed to claustrum, thalamus (deep bundle), and cerebellum were distinguished. By day E28 the first indications of terminal field development were observed. One day before birth (E30), the neonate pattern of subcortical pathways was fully established and silver grain condensations were present over most of the subcortical target areas. Subcortically, the axons followed preferentially preexisting fiber tracts. There was a period of at least 2--3 days between the arrival of the supplying bundles at the target sites and the onset of terminal field formation: The axon bundles grew first towards more distal targets, and even beyond, before terminal fields developed proximally. Transient axon bundles reaching the cerebellar paraflocculus and traveling along the pyramidal tract and the external and extreme capsules failed to form terminal fields and disappeared around birth. The data suggest that growth of long axonal tracts and the development of terminal fields are separate phenomena possibly regulated by different mechanisms.

Age Factors↗

Thalamic connections with limbic cortex. I. Thalamocortical projections.

The thalamocortical projections to limbic cortex in the cat have been studied with retrograde and anterograde axonal transport techniques. Five limbic cortical areas were identified on the basis of cytoarchitecture. The five areas are the anterior limbic area, the cingular area, the dorsal and ventral retrosplenial areas, and the presubiculum. Each of these cortical areas received small injections of horseradish peroxidase, and the afferent thalamic nuclei were identified by retrograde labelling of cells. The cortical projection of each of the anterior thalamic nuclei and the lateral dorsal nucleus was determined autoradiographically. Each of the anterior thalamic nuclei and the lateral dorsal nucleus projects to limbic cortex by two pathways. One group of fibers leaves the rostral thalamus by the fornix, pierces the corpus callosum, joins the cingulate fasciculus to reach limbic cortex. The other group travels through the lateral thalamic peduncle and internal capsule. The anterior ventral nucleus projects primarily to the dorsal retrosplenial area, particularly to layer I, the deep portion of layer II, and superficial portion of layer III. Sparse projections also exist to the ventral retrosplenial area, the cingular area, and the presubiculum. Very sparse projections to the anterior limbic area are seen. The anterior dorsal nucleus projects primarily to the ventral retrosplenial area, particularly layers I, the deep portion of layer II, and superficial layer III. sparse projections exist to the dorsal retrosplenial area and presubiculum, but apparently no projections exist to the cingular or anterior limbic area. The anterior medial nucleus projects primarily to layers I and superficial III of the ventral retrosplenial area. sparse projections exist to each of the other limbic cortical areas. The lateral dorsal nucleus projects extensively onto limbic cortex. Prominent projections occur to layer I, the external granular layer and lamina dessicans of the presubiculum, layers I and III-IV of the dorsal retrosplenial area, and layers I, III, and IV of the cingular area. Sparse projections occur to the ventral retrosplenial area and the anterior limbic areas. Thalamocortical projections also originate in the midline and intralaminar nuclei including the central medial, reuniens, rhomboid, paracentral, central lateral, and central dorsal nuclei. These data indicate that the anterior thalamic nuclei project upon limbic cortex in a complex manner. Further, the projections to limbic cortex from the anterior nuclei overlap with projections from the lateral dorsal nucleus. This overlap of thalamic projections onto limbic cortex suggests a convergence of information from nonprimary sensory systems with information from the classical limbic system.

Animals↗

Thalamic connections with limbic cortex. II. Corticothalamic projections.

The corticothalamic projections from the cat limbic cortex have been investigated with anterograde and retrograde axonal transport techniques. Five limbic cortical areas-the anterior limbic area, the cingular area, the granular and dysgranular retrosplenial areas, and the presubiculum-were identified on the basis of their cytoarchitecture. Emphasis was placed on determining the laminar distribution of the cells of origin of the efferent projections, the projection pathways, and the sites of termination within the thalamus. Projections to the thalamus originate in layers V and VI of limbic cortex. In the cingular region the cells of origin are predominantly in layer V and to a lesser extent in layer VI, while the majority of cells projecting from the more caudal retrosplenial areas and presubiculum are in layer VI. There are two fiber pathways from each cortical area to the thalamus. One system of fibers passes through the internal capsule and lateral thalamic peduncle, and a second system travels in the cingulate fasciculus before piercing the corpus callosum to join the postcommissural fornix. The lateral dorsal nucleus and the anterior nuclear group, including the anterior dorsal, anterior ventral, and anterior medial nuclei, are the major thalamic recipients of projections from limbic cortex. Corticothalamic projections also terminate sparsely in the midline and intralaminar nuclear complex, including the central lateral, central dorsal, paracentral, central medial, rhomboid, and reuniens nuclei. Projections from the anterior limbic area project predominantly to the anterior medial, central lateral, and paracentral nuclei. the anterior ventral nucleus, anterior medial nucleus, and lateral dorsal nucleus are the major thalamic recipients of projections from the cingular area, the granular and dysgranular retrosplenial areas, and the presubiculum. It appears that the anterior dorsal nucleus receives afferents only from the dysgranular retrosplenial area. Bilateral cortico-thalamic projections were found in the anterior medial, dorsal medial, central lateral, central medial, paracentral, and reuniens nuclei.

Animals↗

A collateral pathway to the neostriatum from corticofugal neurons of the rat sensory-motor cortex: an intracellular HRP study.

A projection from large pyramidal cells in layer V of the rat somatic sensory-motor (SSM) cortex both to the neostriatum and the brainstem was demonstrated by intracellular recording and injection of horseradish peroxidase (HRP). Layer V neurons that project to the brainstem were identified either by antidromic activation from the cerebral peduncle or by tracing the HRP-labeled axon into the internal capsule in histochemically processed sections. Intracellular responses to stimulation of the hindlimb, forelimb or mystacial pad were also examined. Five of 20 HRP-injected neurons that project to the brainstem had a fine collateral branch within the striatum. These branched corticostriatal cells respond at short latency (7--12 msec) to somatic sensory stimulation. All of the injected corticofugal neurons that had a striatal collateral were large pyramidal neurons located in layer Vb of the forelimb and head areas of SSM cortex. Branched corticofugal neurons have a rich basal dendritic field and a prominent apical dendrite that arborizes in the superficial cortical layers. Intracortical axon collaterals from the branched cells ramify in layers V and VI, and also project to the upper layers of cortex near the apical dentrite. Beyond the cortex, the main axon has no collateral branches, except for a single laterally directed branch in the neostriatum. The diameter of the striatal collateral is small (about 0.5 micrometer) compared to that of the main axon (2.0--2.5 micrometers). It is concluded that these branched cells provided a parallel input to the neostriatum and to brainstem or spinal motor centers.

Animals↗

Regional (14C) 2-deoxyglucose uptake during vibrissae movements evoked by rat motor cortex stimulation.

Repetitive left mystacial vibrissae movements were produced by electrical stimulation of right motor cortex (MI) were a bipolar electrode in the alert, unanesthetized rat. Regional increases of (14C) 2-deoxyglucose (2DG) uptake were mapped autoradiographically during these left vibrissae movements. Uptake of 2DG increased in a 2-4-mm-diameter area about the stimulating electrode in right MI and in a smaller region in left MI cortex. Columnar increases of 2DG uptake occurred bilaterally in somatosensory cortex in the face region of somatosensory cortex (SI). Bilateral increases of 2DG uptake occurred subcortically in dorsolateral caudate-putamen (CP) and subthalamic nucleus. Primary right-sided increases of 2DG uptake occurred in other basal ganglia structures including dorsal globus pallidus (GP), posterior, entopeduncular nucleus (EPN), ventrolateral substantia nigra pars reticulata (SNr), and anterolateral substantia nigra pars compacta (SNc). Uptake of 2DG increased on the right side of the following thalamic regions: much of the ventrolateral (VL) nucleus, particularly dorsally; the anterodorsal reticular nucleus; dorsolateral posteromedial (POm) nucleus; the ventromedial nucleus; and dorsolateral parafasicular nucleus. The anterior and ventral posterior portions of VL were not activated. Caudal to thalamus right-sided 2DG uptake increased in the medial, ventral, and lateral pontine nuclei, deep layers of superior colliculus, lateral deep mesencephalic nucleus (DMN), and nucleus cuneiformis (NCU). UPtake of 2DG increased in right rostral parvocellular and red nucleus in a few animals. Discrete portions of the right internal capsule and right medial pyramidal tract increased 2DG uptake during MI stimulation. Uptake of 2DG increased on the left side of the brain during right MI stimulation in the left lateral nucleus (NL) of cerebellum and in several discrete regions of left cerebellar hemisphere granule cells including anterior paravermis, lobulus simplex, crus II, and the paramedian lobule. Uptake of 2DG increased in left nucleus of the spinal tract of the trigeminal nerve (ntV) ventrally in subnuclei interpolaris and oralis. Left lateral portions of the facial nucleus were activated in a few animals. The lateral portions of the facial nucleus are known to project to vibrissae musculature. All of the above structures may be involved in the motor-sensory processing responsible for vibrissae movements. Regions not previously suggested to play a major role in vibrissae movements include DMN and NCU. Though NCU has been called the "locomotor center" it may play a role in facial movements as well. Polysynaptic activation of GP, EPN, NL, and cerebellar hemisphere occurred since no connections between MI and these regions exist. A pathway from ntV to POm to MI and SI is suggested to provide proprioceptive input to motor-sensory cortex from the moving vibrissae since neither the principal trigeminal sensory nucleus nor the ventrobasal nucleus of the thalamus increased 2DG uptake during MI stimulation.

Animals↗

Thalamocortical projections in the reeler mutant mouse.

The normal radial distribution of the different neocortical cell classes is inverted in the reeler mutant mouse. The organization of the thalamocortical projection in adult reelers has been investigated by using anterograde degeneration techniques. Thalamocortical axons follow anomalous trajectories to their target cytoarchitectonic fields in the mutant. After leaving the internal capsule, the axons ascend in sigmoid-shaped fascicles to enter a fiber stratum near the cortical surface. The axons course through this superficial stratum until they reach their target fields and then descend to terminate in deeper cortical planes. In the normal animal, by contrast, the axons course tangentially at the interface of the cortex with the subcortical white matter; upon reaching their target fields, they ascend to terminate more superficially in the cortex. Thus, in both genotypes the tangential portions of the axon trajectories pass through the polymorphic cell population. Both with respect to degree of divergence and the radial distribution of terminals within the different cytoarchitectonic fields, the thalamocortical projection in reeler, like that in the normal animal, appears to be composed of two distinct axon classes. The "class I" axons, the less-divergent system which terminates densely in two or three tiers within the cortex, are the subject of the present analysis. The "class I" projections form an orderly cortical representation of the thalamus: Despite distortions in the topography of the reeler thalamus and cortex, both the nucleus to field relationships and the detailed topologic organization of the projection appear to be normal. The terminals of class I projections are distributed in radially segregated tiers that resemble the tiered pattern of termination as in normal mice, and there are field-specific variations in the tiers that, like those of normal mice, are systematically related to variations of cortical cytoarchitecture. Thus, similar mechanisms, which may depend in part on the interaction of ingrowing axons with specific postsynaptic cell surfaces, must determine the restricted radial distribution of thalamocortical projections in both genotypes. However, there is an abnormal mix of somata and dendrites at all radial levels of the mutant cortex, suggesting that the spatial domain of termination of thalamocortical axons may be governed to some extent by factors other than the distribution of specific prospective postsynaptic cell surfaces. The reeler mutation alters the radial but not the tangential structure of the neocortex, suggesting that these two aspects of cortical organization develop under the control of independent mechanisms. The present results suggest that despite the anomalies of radial position, normal relationships between thalamocortical afferents and distinct classes of postsynaptic elements with characteristic radial distributions are largely conserved in reeler. Certain types of aberrant connections are highly probable, however.

Animals↗

Direct cortical projections to the parabrachial nucleus in the cat.

Direct projections from the cerebral cortex to the parabrachial nucleus in the cat were examined by the horseradish peroxidase (HRP)method. When HRP was injected into the parabrachial nucleus, retrogradely labeled neuronal cell bodies were seen, bilaterally with an ipsilateral predominance, mainly in the orbital gyrus, the lateral bank of the presylvian sulcus, and a restricted region in the infralimbic cortex on the medial surface of the frontal lobe (stereotaxic coordinates; Fr: 22, L: 1, H: -1); all labeled neurons were in deep pyramidal cell layer. After injecting HRP conjugated to wheat germ agglutinin (WGA-HRP) into the cortical regions where retrogradely labeled neurons were found after injecting HRP into the parabrachial nucleus, anterogradely labeled cortical fibers were traced to the parabrachial nucleus. Corticoparabrachial fibers originating from the orbital gyrus and the lateral bank of the presylvian sulcus ran ipsilaterally through the internal capsule and the cerebral peduncle down to the lower brainstem, whereas those from the infralimbic cortex coursed down ipsilaterally through the medial forebrain bundle. These cortical fibers to the parabrachial nucleus were distributed bilaterally with an ipsilateral predominance. Cortical fiber terminals in the parabrachial nucleus were topographically arranged: Corticoparabrachial fibers from the lateral bank of the presylvian sulcus ended most massively in the dorsal part of the lateral parabrachial nucleus. Corticoparabrachial fibers from the orbital gyrus ended most heavily in the medial parabrachial nucleus and less heavily in the lateral parabrachial nucleus. Corticoparabrachial fibers from the infralimbic cortex ended mostly in the parabrachial regions surrounding the brachium conjunctivum.

Animals↗

Afferents to the zona incerta in the rat: a combined retrograde and anterograde study.

In a first set of experiments, the retrograde transport of horseradish peroxidase (HRP) was utilized to investigate the afferent projections to the zona incerta (ZI) in the hooded rat. HRP was introduced in its crystalline form into various sectors of the ZI of seven subjects. The largest contingent of afferents arises from the following centers: the cingulate and somatosensory cortices, central amygdaloid nucleus, ventromedial hypothalamic nucleus, posterior thalamic nucleus, anterior pretectal nucleus, peripeduncular area, deep and intermediate layers of the superior colliculus, dorsal and ventral parabrachial nuclei, principal and interpolar trigeminal subnuclei, and cuneate nucleus. Other centers less systematically or more sparsely labeled were the lateral hypothalamic area, ventrobasal complex, lateral geniculate nucleus pars ventralis, medial geniculate nucleus, interstitial nucleus of Cajal, Darkschewitsch nucleus, perirubral fields, cuneiform, tegmental pedunculopontine, and deep mesencephalic reticular nuclei, pontine reticular nucleus pars oralis, lateral and interpositus cerebellar nuclei, and gracile nucleus. In a second set of experiments, an anterograde tracer (WGA-HRP) was injected in several centers projecting to the ZI in order to localize their terminal fields within this structure. It has been thus possible to distinguish a ventral zone (ventral sector of pars caudalis and pars ventralis) in which the somesthetic (somatosensory cortex, trigeminal complex, and dorsal column nuclei (DCN), collicular, and cerebellar projections terminate, from a dorsal zone (pars dorsalis) to which a limbic input (cingulate cortex and ventromedial hypothalamic nucleus) is directed. In most cases, the labeled terminal fields consisted of well-delimited, narrow bands disposed obliquely, parallel to the cerebral peduncle or the internal capsule. The contingent of somatosensory afferents is relatively large and there is a high degree of overlapping between the different somatosensory terminal fields within the ventral ZI. This suggests a participation of this structure in the treatment of somesthetic information and/or in the transmission of noxious stimuli.

Afferent Pathways↗

Axon collaterals in the thalamic reticular nucleus from thalamocortical neurons of the rat ventrobasal thalamus.

Thalamocortical relay neurons from the rat ventrobasal nucleus were identified physiologically and injected intracellularly with horseradish peroxidase. The axons of these cells were followed through serial sections in order to determine if collaterals were given off within the ventrobasal nucleus or the thalamic reticular nucleus. No local collaterals were seen in the ventrobasal nucleus, thus indicating that interactions between relay cells in this nucleus are minimal. Of axons that could be followed into the internal capsule, 76% gave off visible collaterals in the thalamic reticular nucleus. Half of these axons had collaterals showing extensive branching with the potential of innervating a large number of thalamic reticular neurons. The other half had short, simple branches of restricted extent. No correlations were found between the physiological properties of a cell and the existence or extent of axon collaterals. These results describe the anatomical basis for the initial part of a feedback loop through the thalamic reticular nucleus that provides the major inhibitory influence on rat ventrobasal neurons.

Animals↗

Neostriatal projections from cytoarchitectonically defined gyri in the prefrontal cortex of the dog.

The cytoarchitecture and neostriatal projections of the canine prefrontal cortex (PFC) were examined by using Nissl, silver degeneration, autoradiographic, and horseradish peroxidase techniques. Cytoarchitectonically, the PFC can be divided into six major gyral areas with each area corresponding to one of the major gyri--proreal, polar, pregenual, subproreal, paraorbital, and orbital--defined myeloarchitectonically by Kreiner (J. Comp. Neurol. 116:117-133, '61). Of the six major areas, only the proreal gyrus displays a distinctly granular layer IV. In all other gyri, layer IV is more difficult to distinguish. In both the orbital and polar gyri, layer IV is poorly defined and consists of scattered clusters of small cells between layers III and V. In the pregenual, subproreal, and paraorbital gyri, layer IV is not detectable. In all gyri, layer V consists of a thin lamina of small and medium-size pyramidal cells. The transition from layer III to layer V is marked by changes in cell density and size as well as staining intensity. Borders between layers V and VI are generally less distinct than those between layers III and V, with the exception of the pregenual gyrus, in which layer V is separated from layer VI by a distinct cell-poor lamina. In the subproreal and paraorbital gyri, the border between the underlying white matter and layer VI is particularly distinct, with large numbers of neurons oriented tangentially to the white matter. In contrast, the border between layer VI of the orbital gyrus and the white matter is less distinct and consists of palisades of neurons extending well into the white matter. The silver degeneration and autoradiographic methods revealed that prefrontostriatal projections terminate as dorsoventrally oriented longitudinal bands within the medial half of the head and body of the caudate nucleus. Projections from the polar and dorsal proreal gyri terminate most medially in the nucleus while projections from the lateral part of the proreal, subproreal, orbital, and paraorbital gyri terminate progressively more laterally within the medial half of the nucleus. There is apparent overlap between adjacent projection fields. A sparse projection was also noted to a small part of the putamen adjacent to the internal capsule. Injections of horseradish peroxidase into the medial and ventromedial parts of the head of the caudate nucleus resulted in widespread retrograde labeling in parts of the proreal, pregenual, paraorbital, subproreal, and central precruciate gyri. Labeled neurons were located primarily in the superficial part of layer V with smaller numbers of labeled cells in layers III, IV, and VI.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acids↗

Neurogenetic and morphogenetic heterogeneity in the bed nucleus of the stria terminalis.

Neurogenesis and morphogenesis in the rat bed nucleus of the stria terminalis (strial bed nucleus) were examined with [3H]thymidine autoradiography. For neurogenesis, the experimental animals were the offspring of pregnant females given an injection of [3H]thymidine on 2 consecutive gestational days. Nine groups of embryos were exposed to [3H]thymidine on E13-E14, E14-E15,... E21-E22, respectively. On P60, the percentage of labeled cells and the proportion of cells originating during 24-hour periods were quantified at six anteroposterior levels in the strial bed nucleus. On the basis of neurogenetic gradients, the strial bed nucleus was divided into anterior and posterior parts. The anterior strial bed nucleus shows a caudal (older) to rostral (younger) neurogenetic gradient. Cells in the vicinity of the anterior commissural decussation are generated mainly between E13 and E16, cells just posterior to the nucleus accumbens mainly between E15 and E17. Within each rostrocaudal level, neurons originate in combined dorsal to ventral and medial to lateral neurogenetic gradients so that the oldest cells are located ventromedially and the youngest cells dorsolaterally. The most caudal level has some small neurons adjacent to the internal capsule that originate between E17 and E20. In the posterior strial bed nucleus, neurons extend ventromedially into the posterior preoptic area. Cells are generated simultaneously along the rostrocaudal plane in a modified lateral (older) to medial (younger) neurogenetic gradient. Ventrolateral neurons originate mainly between E13 and E16, dorsolateral neurons mainly between E15 and E16, and medial neurons mainly between E15 and E17. The youngest neurons are clumped into a medial "core" area just ventral to the fornix. For morphogenesis, pregnant females were given a single injection of [3H]thymidine during gestation, and their embryos were removed either 2 hours later (short survival) or in successive 24-hour periods (sequential survival). The embryonic brains were examined to locate areas of intensely labeled cells in the putative neuroepithelium of the strial bed nucleus, to trace migratory waves of young neurons, and to establish their final settling locations. Two different neuroepithelial sources produce neurons for the strial bed nucleus. The anterior strial bed nucleus is generated by a neuroepithelial zone at the base of the inferior horn of the lateral ventricle from the anterior commissural decussation area forward to the primordium of the nucleus accumbens.(ABSTRACT TRUNCATED AT 400 WORDS)

Amygdala↗

Frontal eye field efferents in the macaque monkey: I. Subcortical pathways and topography of striatal and thalamic terminal fields.

Anterograde tracers (tritiated leucine, proline, fucose; WGA-HRP) were injected into sites within the frontal eye fields (FEF) of nine macaque monkeys. Low thresholds (less than or equal to 50 microA) for electrically evoking saccadic eye movements were used to locate injection sites in four monkeys. Cases were grouped according to the amplitude of saccades evoked or predicted at the injection site. Dorsomedial prearcuate injection sites where large saccades were elicited were classified as lFEF cases, whereas ventrolateral prearcuate sites where small saccades were evoked were designated sFEF cases. One control case was injected in the medial postarcuate area 6. We found five descending fiber bundles from FEF; fibers to the striatum, which enter the caudate nucleus at or just rostral to the genu of the internal capsule; fibers to the claustrum, which travel in the external capsule; and transthalamic, subthalamic, and pedunculopontine fibers. Our results indicate that transthalamic and subthalamic pathways supply all terminal sites in the thalamus, subthalamus, and tegmentum of the midbrain and pons, whereas pedunculopontine fibers appear to terminate in the pontine and reticularis tegmenti pontis nucleus exclusively. Frontal eye field terminal fields in the striatum were topographically organized: lFEF projections terminated dorsal and rostral to sFEF projections. Thus, lFEF terminal fields were located centrally in the head and body of the caudate nucleus and a small dorsomedial portion of the putamen, whereas sFEF terminal fields were located in ventrolateral parts of the caudate body and ventromedial parts of the putamen. In the claustrum, lFEF projections terminated dorsal and rostral to sFEF projections. Projections from FEF terminated in ventral and caudal parts of the subthalamic nucleus without a clear topography. By comparison, terminal fields from medial postarcuate area 6 were located more caudally and laterally in the striatum and claustrum than projections from FEF, and more centrally in the subthalamic nucleus. In the thalamus, FEF terminal patches in some thalamic nuclei were also topographically organized. Projections from lFEF terminated in dorsal area X, dorsolateral medial dorsal nucleus, pars parvicellularis (MDpc), and the caudal pole of MDpc, whereas projections from sFEF terminated in ventral area X, medial dorsal nucleus, pars multiformis, and caudal medial dorsal nucleus pars densocellularis.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acids↗

Fetal homotypic transplant in the excitotoxically neuron-depleted thalamus: light microscopy.

One month after an in situ injection of kainic acid into the ventrobasal thalamic complex (VB), the lesioned area is totally depleted of neurons. The present study has been undertaken to determine the cytoarchitecture and connectivity of the nucleus constructed by fetal thalamic neurons implanted into the excitotoxically lesioned area. Adult rats received an injection of kainic acid inducing a total neuronal depletion of the right lateral thalamus (including both the nucleus reticularis thalami and the lateral portion of the ventrobasal complex). One month later, homotypic neurons were taken from the dorsal thalamic primordium of rat embryos (gestational age 15-16 days), dissociated, and injected into the lesioned area as a cell suspension. After 2-4-month survival, the cytoarchitecture of the neonucleus formed by the grafted neurons within the previously neuron-depleted area was analyzed. Additionally, connectivity was analyzed in seven rats in which dorsal column nuclei and/or cortical projections to the area were labeled anterogradely with either 3H-leucine or wheat-germ agglutinin conjugated to HRP, and the animals were perfused and processed following various histological procedures (Nissl staining, autoradiographic processing, and histochemistry for visualization of peroxidase). Fetal neurons grew, differentiated, and progressively occupied the previously neuron-depleted area of the adult host CNS. They organized themselves into a neonucleus with particular cytoarchitectural features including 1) the existence of two concentric zones--a central zone containing neurons and glial cells and a marginal zone only filled with a band of glial cells, 2) an increase in cellular density compared to the intact thalamus, 3) the grouping of neurons in spherical clusters, and 4) apparent polymorphism of neuronal somata. Lemniscal and corticothalamic afferents originating from the host were observed in the neonucleus when the fetal neurons had been implanted correctly into the lesioned area but not when they had been misplaced into either normal thalamic tissue or the internal capsule. The afferents labeled from either the dorsal column nuclei or the somatosensory cortex were, however, less dense in the neonucleus than in the normal thalamus. These results are discussed with regard to the normal cytoarchitecture and connectivity of the ventrobasal complex of the rat thalamus.

Animals↗

Telencephalic cholinergic system of the New World monkey (Cebus apella): morphological and cytoarchitectonic assessment and analysis of the projection to the amygdala.

While the cholinergic projection from the nucleus basalis to the cortical mantle has received considerable attention, a similar projection to the magnocellular basal nucleus of the amygdala has not been studied in such detail. The present study analyzed the cholinergic basal forebrain projection to the amygdala in the Cebus apella monkey by using combined tract-tracing and immunocytochemical techniques. As a foundation for this assessment, the morphological and cytoarchitectonic organization of the cholinergic telencephalic system of the New World C. apella monkey was examined by using choline acetyltransferase (ChAT) immunocytochemistry. Although there were minor differences, the telencephalic cholinergic system of Cebus monkeys is similar to that seen in Old World nonhuman primates. ChAT-immunoreactive neurons were observed throughout the Ch1-4 regions of the basal forebrain, with subdivisions of the Ch4 region similar to those previously described (Mesulam et al., '83a). Most cholinergic neurons were hyperchromic and magnocellular; however, some neurons were parvicellular. Like most species, cholinergic neurons were also observed throughout the striatum. However, unlike in rodents, cholinergic perikarya were not observed within the cortex or hippocampus. To analyze the cholinergic fiber projections from the basal forebrain to the amygdala, monkeys received an intraamygdaloid injection of the retrograde tracer horseradish peroxidase conjugated to wheat germ agglutinin. Retrogradely labeled neurons that colocalized ChAT or acetylcholinesterase (AChE) were found predominantly in the anterolateral portion of the CH4 region. Fewer double-labeled neurons were found in the anteromedial and intermediate portion of CH4 and in the CH3 region. Neurons that exhibited retrograde labeling were only occasionally discerned in the posterior portions of the CH4 region, in the medullary laminae of the globus pallidus, or lodged within the internal capsule. These data are discussed in terms of the putative role this cholinergic input might play in cognitive processing in primates.

Acetylcholinesterase↗

Angiotensin converting enzyme in the human basal forebrain and midbrain visualized by in vitro autoradiography.

angiotensin converting enzyme converts angiotensin I to angiotensin II, a peptide that plays an important role in the central regulation of blood pressure and fluid and electrolyte homeostasis. However, the distribution of this enzyme in the human brain has not been well described. In this study, angiotensin converting enzyme was mapped in the human basal forebrain and midbrain by using quantitative in vitro autoradiography employing a derivative of a potent converting enzyme inhibitor, 125I-351A, as radioligand. This radioligand binds specifically and with high affinity to angiotensin converting enzyme and also exhibited these properties in binding to slide-mounted sections of human basal ganglia. In the basal ganglia, high levels of binding of 125I-351A are found in the caudate nucleus, putamen, nucleus accumbens, both divisions of the globus pallidus, and substantia nigra pars reticulata. High densities of labelling also occur in the ventral pallidum. In the hypothalamus, a moderate level occurs in the paraventricular and supraoptic nuclei, and a diffuse, low level of binding is found throughout the periventricular region. The organum vasculosum of the lamina terminalis, one of the circumventricular organs, displays the highest concentration of binding. The choroid plexus contains only moderate density of labelling in contrast to other mammalian species previously studied. Major fibre tracts are devoid of activity except for the posterior limb of the internal capsule, which contains fascicles of intense activity. In the midbrain, a moderate density of binding is detected in the periaqueductal gray. The dorsal, central linear, and, more caudally, the centralis superior medialis raphe nuclei also contain moderate densities of labelling. Angiotensin converting enzyme is heterogeneously distributed in the caudate nucleus and putamen, with distinct patches of high concentration surrounded by a matrix of diffuse, lower levels. In the caudate nucleus, these patches of high binding corresponded to striosomes since they register with acetylcholinesterase-poor zones. The high concentration of angiotensin converting enzyme found in the basal ganglia suggests that the enzyme may be involved in processing neuropeptides that occur in high concentrations in these structures. Possible substrates for converting enzyme include not only angiotensin I but also substance P and enkephalins, which are also concentrated in striosomes.

Aged↗