Efferent connections of the basal forebrain in the cat: the substantia innominata

The efferent connections of the substantia innominata in the cat were studied with radioautographic methods. Injections of [³H]leucine were placed throughout the substantia innominata in 20 cats. The results indicate a complex organization to the efferent distribution of fibers from this region. The projections associated with more caudomedial regions of the substantia innominata resemble those of the adjacent preoptic-hypothalamic area and innervate the septal area, lateral habenular nucleus, and ventral tegmental area. Fibers arising from more caudolateral parts of the substantia innominata (ventral pallidum) appear to project in a crude topographic manner to the amygdala via two routes—the stria terminalis and a second group of caudolaterally directed axons. The fiber distribution from the region of the nucleus basalis is widespread to a variety of cortical sites, such as the olfactory bulb, prefrontal cortex, anterior cingulate gyrus, pyriform, and posterior sylvian cortices. Fibers arising from the rostral aspect of the substantia innominata adjacent to the nucleus accumbens are distributed exclusively to the ventral tegmental area and adjoining substantia nigra. All parts of the substantia innominata supply the ventral tegmental area.     

Ultrastructure of neurons in the nucleus basalis of Meynert in squirrel monkey

The nucleus basalis of Meynert in the squirrel monkey exhibits numerous labeled neurons following the retrograde transport of horseradish peroxidase from occipital cortical injection sites. The typically large, often clustered, labeled cells are seen most frequently in association with the fibrous bordering structures of the substantia innominata and in the internal and external laminae of the globus pallidus. Ultrastructurally the copious cytoplasm of nucleus basalis neurons abounds with organelles. Large, vacuolated lipofuscin granules proliferate as a function of age and are not evident in younger monkeys. Approximately 4% of the somal surface is occupied by symmetrical synapses with either flat or pleomorphic vesicles. The remainder is covered mostly by neuroglial processes. Somatic spines bearing synapses are occasionally observed. In the neuropil surrounding nucleus basalis somata, the synapses onto dendrites and spines are mostly asymmetrical with large, round vesicles. Labeled nucleus basalis cells in the substantia innominata immediately lateral to the optic tract are larger and rounder than cells in the internal and external pallidal laminae. However, no remarkable ultrastructural differences were observed between nucleus basalis somata in the substantia innominata and external pallidal lamina, or between horseradish peroxidase-labeled and unlabeled large cells.     

Limbic and sensory connections of the inferior parietal lobule (area PG) in the rhesus monkey: a study with a new method for horseradish peroxidase histochemistry.

The caudal part of the inferior parietal lobule (area PG) was injected with horseradish peroxidase (HRP) in 6 hemispheres of 5 rhesus monkeys. The retrograde transport of HRP resulted in the labeling of neurons in diverse cortical and subcortical areas. In cortex, labeled neurons were noted in prefrontal cortex (areas 8, 45, 46), in the banks of the intraparietal and superior temporal sulci, in medial parietal cortex, in cingulate cortex, in the retrosplenial area, in area TF and the caudal portions of the parahippocampal region. Subcortical sites with labeled neurons included the necleus basalis of the substantia innominata, the claustrum, the pulvinar and intralaminar thalamic nuclei, the pretectal area, the nucleus locus coeruleus and the raphe nuclei. Although many of the labeled neurons were seen in layers IIIc and V, each cortical area had an individual laminar pattern of labeled neurons. In these experiments, a benzidine dihydrochloride (BDHC) method was used which yields a blue reaction-product at sites containing HRP. BDHC affords superior visibility of labeled neurons, and a significant improvement in sensitivity when compared to a diaminobenzidine procedure in matching series of sections. Additional sections were also stained with a method which allows the simultaneous demonstration of HRP (blue) and acetylcholinesterase (reddish-brown). These revealed that virtually all substantia innominata (nucleus basalis) neurons which project to area PG are also rich in the enzyme acetycholinesterase. These afferents of PG may be classified into 'sensory association', 'limbic' and 'reticular' categories. It is argued that this arrangement of afferent imput may afford a convergence of limbic and sensory information in area PG and that this may subserve a significant function in the process of sensory attention.     

Cortical and subcortical afferent connections of the squirrel monkey's (lateral) premotor cortex: evidence for visual cortical afferents

The afferent connections of the squirrel monkey's lateral premotor cortex were investigated with the horseradish peroxidase (HRP) technique. Seven monkeys received small, unilateral injections of HRP spaced between the most dorsal and the most lateral region of the premotor cortex. Results are based on six brains, all of which showed a considerable number of labeled neurons both cortically and subcortically. At the cortical level, labeled cells were found both ipsi- and contralateral to the injection site. Heavy labeling occurred in the fields surrounding the prefrontal, central, and precentral cortex, while the temporal regions usually innervated the premotor cortex with a moderate number of cells, and the parietal fields with only a minor number. Surprisingly, in all brains, but especially in those with the more lateral injections, we also found a considerable number of afferents originating from occipital fields, including a few neurons from the striate cortex. Subcortically, a few labeled cells were seen in basal forebrain regions, the amygdala, and the claustrum; a considerable number of thalamic nuclei and also some hypothalamic nuclei contained labeled cells; and within the brainstem, labeling was found most consistently in the locus ceruleus and in the tegmental fields. It is concluded that the (lateral) premotor cortex is involved in sensorimotor integration to a higher degree than has been recognized up to now.     

The afferent connections of the substantia innominata in the monkey, Macaca fascicularis

The afferent connections of the substantia innominata and the magnocellular nuclei within it (the nucleus of the horizontal limb of the diagonal band, NHDB, and the nucleus basalis of Meynert, NBM) have been studied with anterograde and retrograde axonal tracing techniques. Prominent inputs arise in the amygdaloid complex, restricted areas of the cerebral cortex, parts of the thalamus and hypothalamus, and nuclei of the lower brainstem. Autoradiographic tracing experiments indicate that the amygdaloid fibers are distributed throughout the NHDB and the NBM, and to a lesser extent to the ventral pallidum. Relatively few fibers innervate the more medially located nucleus of the vertical limb of the diagonal band (NVDB) and the medial septal nucleus. Visualization of the amygdalofugal fibers with the tracer PHA-L (Phaseolus vulgaris leuco-agglutinin) shows that they have varicosities resembling boutons en passant along their length in the substantia innominata. Retrograde tracing experiments using WGA-HRP indicate that the cells of origin of the projection from the amygdala are concentrated in the parvicellular basal nucleus, the caudal part of the magnocellular basal nucleus, the magnocellular accessory basal nucleus, and the central nucleus. Relatively few fibers to the substantia innominata arise in the rostrodorsal part of the magnocellular basal nucleus, or in the lateral or parvicellular accessory basal nuclei. Cortical cells projecting to the substantia innominata were retrogradely labeled in the orbitofrontal cortex (including areas 11-14 and 25), the rostral insula (especially the agranular area), the rostroventral temporal cortex (including areas 35, 36, and parts of TG and TE), and the piriform and entorhinal cortices. The projections from the orbital and rostral temporal cortex were confirmed with anterograde tracers. Projections to the substantia innominata were not found from the more lateral, dorsal or caudal parts of the cerebral cortex, although fibers from temporal area TA may pass through the dendritic field of the most caudal cells of the NBM. Diencephalic cells projecting to the substantia innominata are distributed diffusely throughout the preoptic area and hypothalamus, with higher concentration in the lateral preoptic area and in the pre-, supra-, and tubero-mammillary nuclei. Cells are also found in the midline thalamic nuclei and in the region between the peripeduncular and subparafascicular nuclei.(ABSTRACT TRUNCATED AT 400 WORDS)     

The nucleus basalis of Meynert in neurological dementing disease: a review

The nucleus basalis of Meynert of the substantia innominata supplies the major cholinergic innervation of the cerebral cortex. Pathological alterations have been observed in the nucleus basalis of Meynert in several dementing neurological disorders. This paper is an overview of the work done by several researchers in their attempt to find the possible connections between pathology in the nucleus basalis of Meynert and the clinical symptomatology of dementia in several neurological diseases.     

In situ hybridization localization of choline acetyltransferase mRNA in adult rat brain and spinal cord

The cellular distribution of choline acetyltransferase (ChAT) mRNA within the adult rat central nervous system was evaluated using in situ hybridization. In forebrain, hybridization of a ³⁵S-labeled rat ChAT cRNA densely labeled neurons in the well-characterized basal forebrain cholinergic system including the medial septal nucleus, diagonal bands of Broca, nucleus basalis of Meynert and substantia innominata, as well as in the striatum, ventral pallidum, and olfactory tubercle. A small number of lightly labeled neurons were distributed throughout neocortex, primarily in superficial layers. No cellular labeling was detected in hippocampus. In the diencephalon, dense hybridization labeled neurons in the ventral aspect of the medial habenular nucleus whereas cells in the lateral hypothalamic area and supramammillary region were more lightly labeled. Hybridization was most dense in neurons of the motor and autonomic cranial nerve nuclei including the oculomotor, Edinger-Westphal, and trochlear nuclei of the midbrain, the abducens, superior salivatory, trigeminal, facial and accessory facial nuclei of the pons, and the hypoglossal, vagus, and solitary nuclei and nucleus ambiguus of the medulla. In addition, numerous cells in the pedunculopontine and laterodorsal tegmental nuclei, the ventral nucleus of the lateral lemniscus, the medial and lateral divisions of the parabrachial nucleus, and the medial and lateral superior olive were labeled. Occasional labeled neurons were distributed in the giantocellular, intermediate, and parvocellular reticular nuclei, and the raphe magnus nucleus. In the medulla, light to moderately densely labeled cells were scattered in the nucleus of Probst's bundle, the medial vestibular nucleus, the lateral reticular nucleus, and the raphe obscurus nucleus. In spinal cord, the cRNA densely labeled motor neurons of the ventral horn, and cells in the intermediolateral column, surrounding the central canal, and in the spinal accessory nucleus. These results are in good agreement with reports of the immunohistochemical localization of ChAT and provide further evidence that cholinergic neurons are present within neocortex but not hippocampus.     

An autoradiographic study of the projections of the central nucleus of the monkey amygdala

The efferent connections of the central nucleus of the monkey amygdala have been studied using the autoradiographic method for tracing axonal projections. Small injections of 3H-amino-acids which are largely confined to the central nucleus lead to the labeling of several brainstem nuclei as far caudally as the spinomedullary junction. Specifically, in the forebrain, the central nucleus projects heavily to the bed nucleus of the stria terminalis, the basal nucleus of Meynert, the nucleus of the horizontal limb of the diagonal band, and more lightly to the substantia innominata and the preoptic area. In the hypothalamus, label is found over the dorsomedial nucleus, the perifornical region, the lateral hypothalamus, the supramammillary area, and most heavily in the paramammillary nucleus. In the thalamus, all components of the nucleus centralis medialis and the nucleus reuniens receive fibers from the central nucleus and there is a light projection to the medial pulvinar nucleus. In the mesencephalon, there is heavy labeling dorsal to the substantia nigra ad over the peripeduncular nucleus and lighter labeling within the substantia nigra pars compacta and the ventral tegmental area; the midbrain central gray is also labeled. More caudally, fibers from the central nucleus travel in the lateral tegmental reticular fields and contribute collaterals to the raphe nuclei, the cuneiform nucleus, and the central gray substance. Perhaps one of the heaviest terminal zones is the parabrachial region of the pons, both the lateral and the medial nuclei of which receive a prominent central nucleus projection. Only the ventral aspect of the adjacent locus coeruleus appears to receive a substantial input, but there is labeling also over the area of the nucleus subcoeruleus. Finally, there is heavy labeling around the dorsal motor nucleus of the vagus and over the parvocellular component of the nucleus of the solitary tract. A number of intra-amygdaloid connections between the basal and lateral nuclei of the amygdala and the central nucleus are also described. The present findings, taken together with recently reported widespread projections from the temporal association cortex to the amygdala, point out a potentially trisynaptic route between neocortical association regions and a variety of brainstem nuclei, many of which are related to autonomic function.     

Subset of neurons characterized by the presence of NADPH-diaphorase in human substantia innominata

The substantia innominata encompasses an area of the basal forebrain that is ventral to the lenticular nucleus and anterior commissure, medial to the claustrum and external capsule, and lateral to the hypothalamus. The nucleus basalis of Meynert consists primarily of large acetylcholinesterase (AchE)-positive neurons embedded within the substantia innominata. Damage to these neurons may be important in the pathogenesis of cortical dysfunction in Alzheimer's disease. In order to characterize other neuronal elements in the substantia innominata and their relationship to the nucleus basalis, we chose to study a biochemically distinct neuronal subset containing the enzyme nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d). The substantia innominata was blocked from six normal brains obtained postmortem and fixed in neutral-buffered formalin at 4 degrees C for 48 hours. Free-floating 50-micron sections from several levels were stained for NADPH-d or AchE activities. Selected sections were double stained for NADPH-d and AchE. NADPH-d activity was present in a network of pleomorphic neurons that extended through all levels of the substantia innominata and into the striatum and amygdala. NADPH-d neurons were particularly numerous at the level of the anterior commisure and were closely associated with the cholinergic neurons of the nucleus basalis. They were not seen in the ventral pallidum, or the vertical limb of the diagonal band of Broca or in the islands of Calleja. The cell bodies of NADPH-d neurons were quite varied in shape, ranging from ovoid to fusiform, and about half the cells were bipolar. Where neuronal density was high, their dendrites formed an interlacing pattern. NADPH-d-positive fibres were seen coursing through the external capsule, hypothalamus, and amygdala. This novel set of neurons in the substantia innominata may be part of a more extensive network that interacts with the magnocellular basal forebrain system at the level of the nucleus basalis. Whether other neurotransmitters are present within these neurons and whether NADPH-d neurons are involved in Alzheimer's disease remain to be elucidated.     

Subcortical afferents to the hippocampal formation in the monkey

The distribution of neurons in the basal telencephalon, the diencephalon, and the brainstem that project to the hippocampal formation has been analyzed in mature cynomolgus monkeys (Macaca fascicularis) by the injection of horseradish peroxidase into different rostro-caudal levels of the hippocampal formation. After injections which involve Ammon's horn, the dentate gyrus, and the subicular complex, retrogradely labeled neurons are found in the following regions: in the amygdala (specifically in the anterior amygdaloid area, the basolateral nucleus, and the periamygdaloid cortex); in the medial septal nucleus and the nucleus of the diagonal band; in the ventral part of the claustrum; in the substantia innominata and the basal nucleus of Meynert; in the rostral thalamus (specifically in the anterior nuclear complex, the laterodorsal nucleus, the paraventricular and parataenial nuclei, the nucleus reuniens, and the nucleus centralis medialis); in the lateral preoptic and lateral hypothalamic areas, and especially in the supramammillary and retromammillary regions; in the ventral tegmental area, the tegmental reticular fields, the raphé nuclei (specifically in nucleus centralis superior and the dorsal raphé nucleus), in the nucleus reticularis tegmenti pontis, the central gray, the dorsal tegmental nucleus, and in the locus coeruleus.     

Cholinergic neurons in the basal forebrain of the cat have direct projections to the sensorimotor cortex

Previous studies showed that projections from the cells in the substantia innominata to the sensorimotor cortex exist in the monkey and rat and that this group of cortical afferent fibers utilizes acetylcholine as a neurotransmitter. Because similar studies have not been made in the cat, the following study was undertaken to analyze the extent and distribution of this projection from the basal forebrain. Horseradish peroxidase (HRP) injections were made into the anterior and posterior sigmoid gyri 24 h before, and diisopropyl fluorophosphate was injected intramuscularly 3 h before the anesthetized cats were perfused. Brain sections from these cats were incubated in solutions to simultaneously detect retrogradely transported HRP and acetylcholinesterase (AChE) reaction product within the somata. The cell bodies that contained reaction product for both HRP and AChE were mostly large (25 to 30 μm) and multipolar. These double-labeled cells were located in (i) the nucleus of the diagonal band in rostral sections, (ii) the globus pallidus, entopeduncular nucleus, and substantia innominata at the level of the anterior commissure, and (iii) the lateral hypothalamus in the most caudal sections. Many of these sites corresponded to that for the basal nucleus of Meynert, an aggregation of large multipolar neurons scattered throughout the basal forebrain. Although the presence of AChE within a cell does not define a cholinergic neuron, recent studies indicated that its presence is a requirement for this neurotransmitter. These data together with biochemical and immunocytochemical data indicate that a cholinergic projection to the sensorimotor cortex of cats arises from the basal forebrain. This pathway may play a vital role in memory and cognition.     

An experimental study of the ventral striatum of the golden hamster. I. Neuronal connections of the nucleus accumbens

As part of an experimental study of the ventral striatum, the horseradish peroxidase (HRP) method was used to examine the afferent and efferent neuronal connections of the nucleus accumbens. Following iontophoretic applications or hydraulic injections of HRP in nucleus accumbens, cells labeled by retrograde transport of HRP were observed in the ipsilateral telencephalon in the posterior agranular insular, perirhinal, entorhinal, and primary olfactory cortices, in the subiculum and hippocampal field CA1, and in the anterior and posterior divisions of the basolateral amygdaloid nucleus. In the diencephalon, labeled neurons were present ipsilaterally in the central medial, paracentral and parafascicular intralaminar nuclei, and in the midline nuclei parataenialis, paraventricularis, and reuniens. Retrograde labeling was observed in the ipsilateral brainstem in cells of the ventral tegmental area and dorsal raphe. Many of these projections to nucleus accumbens were found to be topographically organized. Anterograde transport of HRP from nucleus accumbens demonstrated ipsilateral terminal fields in the ventral pallidum and substantia nigra, pars reticulata. The afferent projections to nucleus accumbens from the posterior insular and perirhinal neocortices, intralaminar thalamus, and the dopamine-containing ventral tegmental area are analogous to the connections of the caudatoputamen, as are the efferents from nucleus accumbens to the substantia nigra and ventral globus pallidus. These connections substantiate the classification of nucleus accumbens as a striatal structure and provide support for the recently proposed concept of the ventral striatum. Furthermore, the demonstration that a number of limbic system structures, including the amygdala, hippocampal formation, entorhinal cortex, and olfactory cortex are important sources of afferents to the nucleus accumbens, suggests that the ventral striatum may serve to integrate limbic information into the striatal system.     

Basal forebrain efferents reach the whole cerebral cortex of the cat

Efferent projections from the basal forebrain to the cat's cerebral cortex were traced with the retrograde horseradish peroxidase technique. Different areas of the cerebral cortex of 51 cats were injected with small amounts of horseradish peroxidase. The entire basal forebrain was screened for labeled neurons. Following all injections, retrogradely labeled neurons could be detected in either the medial septum, or the vertical and horizontal limb of the diagonal band of Broca, or the substantia innominata, or in several of these structures. All three basal forebrain structures project heavily to allocortical regions, but only weakly to neocortical regions. An exception is the medial prefrontal cortex which is densily innervated by the substantia innominata (i.e., comparably dense as allocortical regions are innervated by the substantia innominata). Large injections into he basal temporal cortex (including the perirhinal cortex) and into the insular cortex also led to a considerable number of labeled cells in the substantia innominata. The results indicate a widespread innervation of the cat's cerebral cortex by the basal forebrain. This diffuse projection to the cortex has recently been found also in monkeys and rats. Anatomical and functional implications of these projections in the cat are discussed and related to findings in other species.     

Afferent fibers to the cingular vocalization region in the squirrel monkey

Three squirrel monkeys (Saimiri sciureus) received horseradish peroxidase injections in the anterior cingulate cortex at the level of the genu of the corpus callosum, a region yielding vocalization when electrically stimulated. Retrogradely labeled neurons were found at the cortical level within the dorsomedial and lateral prefrontal cortex (areas 9 and 10), orbital cortex (area 11), premotor cortex (areas 44, 6b, and 8), frontoparietal operculum, insula, cortex of the superior temporal sulcus, piriform cortex, subiculum, posterior cingulate, and retrosplenial cortex. Subcortical telencephalic projections came from the the claustrum, diagonal band of Broca, nucleus basalis Meynert, nuclei basalis lateralis and accessorius amygdalae, and cells at the periphery of globus pallidus. Diencephalic structures projecting to the anterior cingulate cortex were the thalamic nuclei anterior medialis, anterior ventralis, ventralis anterior, ventralis lateralis pars medialis, medialis dorsalis, pulvinaris medialis, centralis superior lateralis and limitans; the intralaminar nuclei paracentralis, centralis lateralis and parafascicularis; and the midline nuclei periventricularis, parataenialis, centralis superior, centralis inferior, centralis medialis, and reuniens. In the hypothalamus, projections came from the periventricular, lateral and posterior part, as well as the supramamillary nucleus. Midbrain afferent fibers came from the ventral tegmental area of Tsai, medial substantia nigra, reticular formation, area praerubralis, nucleus peripeduncularis, and periaqueductal gray. The most posterior labeled neurons were found in the locus ceruleus, dorsal tegmental nucleus of Gudden, nucleus annularis, nucleus centralis superior Bechterew, nucleus dorsalis raphae and the most dorsomedial part of the nucleus reticularis tegmenti pontis. Some of those projections have functional significance in the light of the hypothesis that the cingular cortex is involved in the volitional control of emotional reactions on the one hand and the influence of primary emotional reactions on intentional behavior on the other.     

Afferents to the ventral tegmental nucleus of Gudden in the mouse, rat, and cat

Afferents to the ventral tegmental nucleus of Gudden (VT) were investigated in mice, rats, and cats. Unilateral and bilateral injections or iontophoretical applications of horseradish peroxidase (HRP) were made into the region of the VT. The entire cerebrum was then screened for labeled neurons. Following injections situated principally within the VT, in all three species many retrogradely labeled neurons were observed in the mamillary bodies and the lateral habenular nuclei. Fewer labeled cells were observed in the prefrontal cortex, the basal forebrain, various hypothalamic nuclei, the interpeduncular nucleus, nucleus of the posterior commissure, nucleus of Darkschewitsch and interstitial nucleus of Cajal, vestibular nucleus, and nucleus praepositus hypoglossi. Scant but consistent labeling occurred in the cingular, retrosplenial, and insular cortices, within the medial forebrain bundle, fields of Forel, zona incerta, ventral tegmental area of Tsai, substantia nigra, pretectal area, periaqueductal gray, dorsal tegmental nucleus, locus ceruleus, and raphe complex. Our results show a high similarity in the distribution of afferent connections converging on the VT of mice, rats, and cats. They indicate furthermore that the VT is reached by a variety of cortical and subcortical afferents, which belong either to the limbic system or to brain stem regions related to motor, sensory, and autonomic functions. It is suggested that the VT subserves as a midbrain core structure of the limbic system, which is responsible for the transfer of motor, sensory, and autonomic informations arising within the brain stem to limbic forebrain structures.     

Distribution of pre-pro-glucagon and glucagon-like peptide-1 receptor messenger RNAs in the rat central nervous system

Glucagon-like peptide-1 (GLP-1) is derived from the peptide precursor pre-pro-glucagon (PPG) by enzymatic cleavage and acts via its receptor, glucagon-like peptide-1 receptor (GLP-1R). By using riboprobes complementary to PPG and GLP-1R, we described the distribution of PPG and GLP-1R messenger RNAs (mRNAs) in the central nervous system of the rat. PPG mRNA-expressing perikarya were restricted to the nucleus of the solitary tact or to the dorsal and ventral medulla and olfactory bulb. GLP-1R mRNA was detected in numerous brain regions, including the mitral cell layer of the olfactory bulb; temporal cortex; caudal hippocampus; lateral septum; amygdala; nucleus accumbens; ventral pallium; nucleus basalis Meynert; bed nucleus of the stria terminalis; preoptic area; paraventricular, supraoptic, arcuate, and dorsomedial nuclei of the hypothalamus; lateral habenula; zona incerta; substantia innominata; posterior thalamic nuclei; ventral tegmental area; dorsal tegmental, posterodorsal tegmental, and interpeduncular nuclei; substantia nigra, central gray; raphe nuclei; parabrachial nuclei; locus ceruleus, nucleus of the solitary tract; area postrema; dorsal nucleus of the vagus; lateral reticular nucleus; and spinal cord. These studies, in addition to describing the sites of GLP-1 and GLP-1R synthesis, suggest that the efferent connections from the nucleus of the solitary tract are more widespread than previously reported. Although the current role of GLP-1 in regulating neuronal physiology is not known, these studies provide detailed information about the sites of GLP-1 synthesis and potential sites of action, an important first step in evaluating the function of GLP-1 in the brain. The widespread distribution of GLP-1R mRNA-containing cells strongly suggests that GLP-1 not only functions as a satiety factor but also acts as a neurotransmitter or neuromodulator in anatomically and functionally distinct areas of the central nervous system. J. Comp. Neurol. 403:261–280, 1999. © 1999 Wiley-Liss, Inc.     

The afferent input to the magnocellular division of the mediodorsal thalamic nucleus in the monkey, Macaca fascicularis

The origin and termination of fibers to the mediodorsal thalamic nucleus, especially those to the medial, magnocellular part of the nucleus (MDm), have been studied using anterograde and retrograde axonal tracing methods, as well as electrophysiological recording. The results indicate that in addition to its well-known connections to and from the prefrontal cortex, MDm receives fibers from many parts of the basal forebrain, including the ventral pallidum and other parts of the substantia innominata, the amygdaloid complex, the primary olfactory cortex, entorhinal and perirhinal cortex, and the cortex at the pole of the temporal lobe. Lighter projections arise in the subiculum, the ventral insula, and the superior and inferior temporal gyri. The cells that project to MDm tend to be large, polymorphic neurons. Throughout most of the basal forebrain they are diffusely distributed through several nuclei or cortical layers, without obvious relation to nuclear or laminar boundaries. The major exception to this is in the ventral pallidum, where there is a dense concentration of cells that project to MDm. The lateral part of the mediodorsal nucleus (MDl) receives few if any fibers from the basal forebrain and temporal lobe, but is innervated by several brainstem structures, especially the superior colliculus, the substantia nigra, the medial vestibular nucleus, and the midbrain tegmental fields. In MDm, the fibers are distributed in irregular patches. Three-dimensional analysis indicates that these patches are often clustered into separate bands or columns at different anteroposterior levels. In addition, the strongest projections from the three major regions that innervate MDm are organized in a complex three-dimensional pattern. First, the fibers from the amygdaloid nuclei terminate most heavily (but not exclusively) in the rostral third of MDm. The parvicellular accessory basal amygdaloid nucleus and the amygdalohippocampal area project principally to the dorsal part of the nucleus. The parvicellular basal nucleus and the periamygdaloid cortex project to the ventromedial quadrant of MDm; and the magnocellular basal nucleus, the magnocellular accessory basal nucleus, and the lateral nucleus all project to the ventrolateral quadrant. Second, the substantia innominata projects preferentially to the caudal part of MDm. The medial part of the substantia innominata, especially the ventral pallidum, innervates the dorsomedial quadrant, while more caudal and lateral areas of this region project ventrolaterally. Third, the projections arising from the entorhinal and other temporal cortical areas terminate primarily in the mid-rostrocaudal level of MDm.(ABSTRACT TRUNCATED AT 400 WORDS)     

Loss of neurons in the nucleus basalis of Meynert in Alzheimer's disease,paralysis agitans and Korsakoff's disease

Summary The nucleus basalis of Meynert, the major source of cholinergic innervation of the cerebral cortex, was morphometrically investigated in 58 cases of neuropsychiatric disorders and compated to 14 controls. The results demonstrate a loss of neurons in the nucleus basalis of Meynert in Alzheimer's disease (70%), paralysis agitans (77%), and Korsakoff's disease (47%) but no marked reduction of neurons in postencephalitic parkinsonism, Huntington's disease, chronic alcoholism without dementia, schizophrenia and infantile brain damage. Neurons of the three subdivisions of the nucleus basalis of Meynert (the nucleus septi medialis, the nucleus of the diagonal band of Broca and the nucleus basalis Meynert neurons in the substantia innominata) may be affected in a different manner in different patients within a single group homogeneous with respect to the usual clinical and neuropathological diagnostic criteria. Cell loss in the basal forebrain is restricted to the large neurons of the nucleus basalis, the immediately adjacent neurons of the globus pallidus externus not being affected. The selective degeneration of these neurons provides the morphological correlate of the cortical cholinergic deficiency in these neuropathological conditions. The degeneration of this discrete cholinergic neuronal population in several disorders of higher cortical function is probably directly related to the progressive deterioration of memory and cognitive processes in affected patients.     

Erratum

Tritiated tracer was injected into the head of the caudate nucleus in cats. Following such injections, labeling is present within extensive regions of both the globus pallidus and entopeduncular nucleus, where it presents a mottled or meshlike appearance. These projections are topographically organized in that there is simple correspondence between the mediolateral, dorsoventral, and rostrocaudal origin of the caudate projection and its input to the globus pallidus and entopeduncular nucleus. Transported tracer is also present within the substantia nigra, where it is most abundant within the pars reticularis. However, distinct labeling also overlies cells of the pars corapacta, and lesser amounts of labeling are present within the pars lateralis and within the retrorubral area. Following injections of horseradish peroxidase into the caudate nucleus, and subsequent tissue processing by the tetramethylbenzidine (TMB) method of Mesulam (1978), labeled anterograde fibers are present in abundance within the globus pallidus, entopeduncular nucleus, and all subdivisions of the substantia nigra, thus confirming the autoradiographic findings. Also, it is especially obvious in this HRP material that, contrary to previous degeneration studied, both the rostromedial and caudolateral parts of the pars reticularis of the substantia nigra contain numerous anterogradely labeled fibers. Retrogradely labeled neurons are also present within the substantia nigra of these same tissue sections, where they are most abundant within the pars compacta, but lesser numbers of labeled neurons are also present within the pars reticularis, pars lateralis, retrorubral area, and ventral tegmental area on the ipsilateral side, and all of these same subdivisions of the substantia nigra on the contralateral side. Also, within the subthalamic nucleus in these experiments, there are anterogradely labeled fibers, as well as retrogradely labeled neurons, which are interpreted to represent a reciprocal connection between the subthalamic nucleus and the striatum. In a separate series of experiments, horseradish peroxidase was injected into the motor cortex–specifically into the anterior sigmoidal gyrus. Following such injections, labeled neurons representing afferents to the motor cortex are found in all subcortical nuclei commonly known as the “basal ganglia,” including the caudate nucleus, putamen, globus pallidus, entopeduncular nucleus, substantia innominata, nucleus of the diagonal band of Broca, medial septal nucleus, claustrum, and basolateral amygdaloid nucleus.     

An experimental study of the ventral striatum of the golden hamster. II. Neuronal connections of the olfactory tubercle

As part of an experimental study of the ventral striatum, the horseradish peroxidase (HRP) method was used to examine the afferent and efferent neuronal connections of the olfactory tubercle. Following iontophoretic applications or hydraulic injections of HRP in the tubercle, neurons labeled by retrograde transport of HRP were observed ipsilaterally in the telencephalon in the main olfactory bulb, the medial, lateral, ventral, and posterior divisions of the anterior olfactory nucleus, and in the orbital, ventral, and posterior agranular insular, primary olfactory, perirhinal, and entorhinal cortices. Labeled cells were also present in the basolateral, basomedial, anterior cortical, and posterolateral cortical amygdaloid nuclei, and bilaterally in the nucleus of the lateral olfactory tract. In the diencephalon, ipsilateral HRP-containing neurons were observed in the midline nuclei paraventricularis, parataenialis, and reuniens, and in the parafascicular intralaminar nucleus. Retrograde labeling was present in the ipsilateral brainstem in cells of the ventral tegmental area, substantia nigra, and dorsal raphe. Many of the above projections to the tubercle were found to be topographically organized. Anterograde axonal transport of HRP from the olfactory tubercle labeled terminal fields ipsilaterally in all parts of the anterior olfactory nucleus, in the ventral pallidum, and in the substantia nigra, pars reticulata. Contralaterally, terminal fields were present in the dorsal and lateral divisions of the anterior olfactory nucleus. The projections to the tubercle from the orbital, ventral, and posterior agranular insular, and perirhinal neocortices, intralaminar thalamus, and dopamine-containing areas of the ventral mesencephalon are analogous to the connections of the caudatoputamen, as are the efferents from the tubercle to the ventral globus pallidus and substantia nigra. These connections substantiate the recent suggestion that the olfactory tubercle is a striatal structure, and provide support for the ventral striatal concept. In the present study of the olfactory tubercle, and in the first study in this series on the nucleus accumbens, the ventral striatum was found to receive projections from a number of limbic system structures, including the main olfactory bulb, anterior olfactory nucleus, amygdala, hippocampus, and subiculum, and the entorhinal and primary olfactory cortices. These findings suggest that the ventral striatum is concerned with integrating limbic information into the striatal system.