Biomedical subjects

L Heimer

Publications and source records attributed to L Heimer.

At least 37 records · Page 2Linked to original sources

PubMed1990

In vivo anterograde and retrograde axonal transport of the fluorescent rhodamine-dextran-amine, Fluoro-Ruby, within the CNS.

A number of fluorescent dextrans were screened for axonal transport properties within the rat CNS. One compound, Fluoro-Ruby (FR), was found to be particularly sensitive for demonstrating retrograde and particularly anterograde axonal transport. The tracer may be either pressure or iontophoretically injected, and the fixed tissue can be examined without histochemical processing. The technique can be combined with a wide variety of other neuroanatomical methods.

Animals↗

PubMed1990

The basal forebrain projection to the region of the nuclei gemini in the rat; a combined light and electron microscopic study employing horseradish peroxidase, fluorescent tracers and Phaseolus vulgaris-leucoagglutinin.

We have examined the location of basal forebrain cells projecting to the region of the nuclei gemini in the caudolateral hypothalamus of the rat using retrograde transport of wheatgerm agglutinin-horseradish peroxidase. Since many tracer-positive neurons were identified in ventral pallidal areas known to project to the mediodorsal nucleus of the thalamus, we also prepared several animals with wheatgerm agglutinin-horseradish peroxidase injections in mediodorsal thalamus. Many of the sections from both groups of animals were subsequently prepared for the demonstration of ventral pallidal regions, using either substance P or glutamate decarboxylase as a pallidal marker. Some animals received injections of different retrogradely transported fluorescent tracers in the mediodorsal thalamus and the nuclei gemini for the purpose of studying potential axon collateralization. The large gemini-projecting cells are diffusely scattered within the medial forebrain bundle area, from the caudal margin of the nucleus of the horizontal limb of the diagonal band to the rostral tip of the olfactory tubercle, and with a concentration of cells in the lateral part of the medial forebrain bundle region. Gemini-projecting cells were not found in the olfactory tubercle proper, including the islands of Calleja complexes, or in the ventral pallidal areas located dorsal to the medial forebrain bundle area underneath the lateral extension of the anterior commissure. Gemini-projecting cells within ventral pallidal areas were observed only in regions where the longitudinal fascicles of the medial forebrain bundle interdigitate with the rostroventral extension of the ventral pallidum. Anterogradely-labeled fiber plexuses in the region of the nuclei gemini were observed following injection of Phaseolus vulgaris-leucoagglutinin or Fluoro-Ruby into the forebrain regions containing retrogradely-labeled neurons following nuclei gemini injections of wheatgerm agglutinin-horseradish peroxidase. We found no evidence of cells with axonal projections to both mediodorsal thalamus and nuclei gemini. The gemini-projecting cells are generally large, triangular and plump, and the electron microscopic picture of gemini-projecting neurons is the same regardless of whether the cells are located in pallidal or non-pallidal areas.

Animals↗

PubMed1990

Iontophoretic injection of fluoro-gold and other fluorescent tracers.

Fluoro-gold, a retrograde axonally transported fluorescent tracer, has been successfully iontophoresed into brain regions to yield small injection sites with no detectable dye along the track. Previous difficulties involving iontophoretic application of fluoro-gold were overcome through the use of a cacodylate vehicle. This vehicle was also found to be suitable for iontophoresing other fluorescent tracers, such as propidium iodide or Fast Blue.

Animals↗

PubMed1988

Ventral striatopallidal parts of the basal ganglia in the rat: I. Neurochemical compartmentation as reflected by the distributions of neurotensin and substance P immunoreactivity.

The distribution of neurotensin immunoreactivity in the basal ganglia of the adult rat was evaluated by studying alternate serial vibratome sections that were exposed to antiserum against neurotensin, substance P, or cholecystokinin. It was observed that a heterogeneous distribution of neurotensin-immunoreactive fibers and terminals contributes to the neurochemical compartmentation of the ventral pallidum and ventral striatum, and that significant numbers of neurotensin-immunoreactive neurons occupy striatal districts of the olfactory tubercle, nucleus accumbens, and ventromedial caudate-putamen. An intense band of pallidal neurotensin immunoreactivity characterizes the medial part of the ventral pallidum adjacent to the nucleus accumbens, whose medial boundary is conveniently defined in sections incubated with cholecystokinin antiserum. Electron microscopic studies showed that the pallidal plexus of neurotensin-immunoreactive elements consists primarily of boutons, which contact large dendrites in arrangements that in all respects appear to be of the classical striatopallidal variety. A gradual decrease in immunolabel was observed approaching the lateral parts of the ventral pallidum, which display sparse neurotensin immunoreactivity. The results thus indicate the existence of a significant neurotensinergic striatopallidal pathway confined primarily, if not exclusively, to the medial part of the ventral striatopallidal system. The contribution of neurotensin-immunoreactive fibers and terminals to the compartmentation of ventral striatum is expressed most vividly in their exclusion from clusters of tightly packed medium-sized neurons, many of which are intensely substance P immunoreactive. Such clusters appear identical with those previously described as rich in opiate receptors and poor in acetylcholinesterase activity. In the ventral striatal region where the nucleus accumbens and ventromedial caudate-putamen merge, neurotensin-immunoreactive neurons are organized in clusters. Further rostral in the nucleus accumbens, they are more evenly distributed. Few were found in the dorsolateral quadrant of the neostriatum.

Animals↗

PubMed1988

The basolateral amygdaloid complex as a cortical-like structure.

The thalamic innervation of the rat basolateral amygdaloid complex was studied with a combination of light- and electron microscopic techniques using anterogradely transported Phaseolus vulgaris-leucoagglutinin (PHA-L) as well as combined degeneration and single-section Golgi impregnation for the identification of thalamo-amygdaloid synaptic relations. The results indicated that the basolateral amygdaloid nucleus corresponds in several features to a cortical structure. Like all cortical areas, the basolateral amygdaloid nucleus is reciprocally related to other cortical regions as well as to the thalamus.

Amygdala↗

PubMed1988

New perspectives in basal forebrain organization of special relevance for neuropsychiatric disorders: the striatopallidal, amygdaloid, and corticopetal components of substantia innominata.

The basal forebrain is critically involved in functions representing the highest levels of integration. Only recently has a relatively clear anatomical picture of this important area begun to emerge. The territory that has generally been referred to as the "substantia innominata" appears to be composed of portions of three recognizable forebrain structures: the ventral striatopallidal system, the extended amygdala and the magnocellular corticopetal system. (1) Rostrally, the striatopallidal system reaches ventrally to the base of the brain. (2) Caudal to the ventral extension of the striatopallidal system elements of the centromedial amygdala and bed nucleus of the stria terminalis are merged so that these two areas together with this subpallidal corridor form a large forebrain unit that might be described as an "extended amygdala". (3) Large cholinergic and non-cholinergic corticopetal neurons form a more or less continuous aggregate that is interwoven with the striatopallidal and extended amygdala systems in basal forebrain. Consideration of morphological and connectional characteristics of basal forebrain suggests that the corticopetal cell groups, together with magnocellular elements of the striatum, serve similar functional roles for the striatopallidal system, the extended amygdala, and the septal-diagonal band complex. Specifically, the output of medium spiny neurons in striatum, extended amygdala, and lateral septum are directed toward somewhat larger sparsely or moderately spiny neurons with radiating dendrites which in turn project to diencephalon and brainstem or provide either local feedback (e.g. in striatum) or distal feedback to cortex. The functional implications of this parallel processing of descending forebrain afferents are discussed.

Amygdala↗

PubMed1987

The ventral striatopallidothalamic projection. III. Striatal cells of the olfactory tubercle establish direct synaptic contact with ventral pallidal cells projecting to mediodorsal thalamus.

After injection of HRP in the thalamic mediodorsal nucleus (MD) of the rat on one side followed by a superficial laminar heat lesion of the olfactory tubercle (Tu) on the same side, electron microscopic examination of DAB-reacted sections through the Tu revealed degenerating terminals contacting HRP-labeled neurons, confirming that a monosynaptic, two-neuron link extends, via a relay in ventral pallidum, between the superficial dense cell layer of the Tu and the MD.

Animals↗

PubMed1987

The ventral striatopallidothalamic projection: I. The striatopallidal link originating in the striatal parts of the olfactory tubercle.

The projections from the striatal part of the olfactory tubercle were examined in rats, both with the aid of experimental silver impregnation methods following superficial laminar heat lesions of the tubercle and by the use of anterograde transport of Phaseolus vulgaris-leucoagglutinin (PHA-L) following injections of the lectin in the dense cell layer of the tubercle. Retrograde transport of fluorescent substances following injections of the tracer in the multiform layer of the tubercle were used to corroborate the results obtained by the anterograde transport and degeneration methods. The main and apparently only significant termination from the striatal cells in the olfactory tubercle is located immediately deep to the dense cell layer in areas that could be identified as part of the ventral pallidum on the basis of either the Nissl method or glutamate decarboxylase immunocytochemistry. Whereas a mediolateral topography is generally maintained by the ventral striatopallidal pathway originating in the dense cell layer, there is a considerable spread of the projection in the rostrocaudal direction. The dense projection field of the olfactory tubercle component of the ventral striatopallidal pathway permeates the ventrolateral part of the ventral pallidum, thereby complementing the termination of the accumbens projection to the more mediodorsal parts of the ventral pallidum.

Animals↗

PubMed1987

The ventral striatopallidothalamic projection: II. The ventral pallidothalamic link.

The projection of ventral pallidal neurons to the mediodorsal nucleus of the thalamus (MD) was examined in rats by combined retrograde transport of horseradish peroxidase (HRP) after injections in the MD and glutamate decarboxylase (GAD) immunocytochemistry at light and electron microscopic levels, with and without prior exposure of the brains to colchicine. HRP was transported to the soma of medium-sized and large ventral pallidum neurons, which along with their long, large dendrites were contacted by many glutamate decarboxylase immunoreactive synaptic boutons. The retrograde tracer positive neurons bore a remarkable resemblance to the projecting cells of the globus pallidus and entopeduncular nucleus. When colchine exposure was included in the tissue preparation, some but not all tracer positive cells also exhibited cytoplasmic GAD immunoreactivity.

Animals↗

PubMed1986

GABAergic input to cholinergic forebrain neurons: an ultrastructural study using retrograde tracing of HRP and double immunolabeling.

Amygdalopetal cholinergic neurons in the ventral pallidum were identified by combining choline acetyltransferase (ChAT) immunohistochemistry with retrograde tracing of horseradish peroxidase (HRP) following injections of the tracer in the basolateral amygdaloid nucleus. Although ChAT-positive terminals were identified in the ventral pallidum, they were never seen in contact with either immunonegative or ChAT-positive amygdalopetal neurons. In material, in which immunostaining against glutamic acid decarboxylase (GAD), the synthesizing enzyme for GABA was combined with retrograde tracing of HRP from the basolateral amygdaloid nucleus, GAD-positive terminals were seen to contact immunonegative amygdalopetal neurons. In addition, when sections of the rostral forebrain were processed, first to preserve and identify the transported HRP, and then were sequentially tested for both ChAT and GAD immunohistochemistry with the immunoperoxidase reaction for both tissue antigens, GAD-immunopositive terminals were seen to make synaptic contacts with cholinergic amygdalopetal neurons. These results suggest that amygdalopetal, presumably cholinergic, neurons receive GAD-positive terminals. In separate experiments using immunoperoxidase for ChAT and ferritin-avidin for GAD labeling, we confirmed the presence of GAD-containing terminals on cholinergic neurons. In addition, cholinergic terminals were seen in synaptic contact with GAD-positive cell bodies. These morphological studies suggest that direct GABAergic-cholinergic and cholinergic-GABAergic interactions take place in the rostral forebrain.

Amygdala↗

PubMed1986

The projection from the parataenial thalamic nucleus, as demonstrated by the Phaseolus vulgaris-leucoagglutinin (PHA-L) method, identifies a subterritorial organization of the ventral striatum.

The thalamic projection to the ventral striatum was examined in the rat by immunohistochemistry after iontophoretic injections of Phaseolus vulgaris-leucoagglutinin (PHA-L) into the parataenial thalamic nucleus. A continuous dense terminal field was observed in the nucleus accumbens and the striatal cell bridges, as well as in the adjoining striatal parts of the olfactory tubercle. These observations provide further evidence of the relevance of the ventral striatal concept.

Animals↗

PubMed1986

A correlated light and electron microscopic immunocytochemical study of cholinergic terminals and neurons in the rat amygdaloid body with special emphasis on the basolateral amygdaloid nucleus.

The cholinergic innervation of the rat basolateral amygdaloid nucleus (BL) was determined by the immunocytochemical localization of the acetylcholine biosynthetic enzyme, choline acetyltransferase (ChAT). ChAT-immunoreactive (ChAT-IR) elements were observed throughout the BL in the form of fine puncta and varicose fibers. Electron microscopy revealed that the immunoreactive puncta represented small terminals (0.3-1.2 micron), most of which formed synaptic contacts with unlabeled dendritic shafts or spines. Less frequently, ChAT-IR terminals established synaptic contacts with large neuronal cell bodies, which had all the characteristics of projection neurons as defined on the basis of axonal projections to the ventral striatum. ChAT-IR terminals were sometimes seen to form synaptic contacts with small neuronal cell bodies, including those of ChAT-IR neurons. The ChAT-IR boutons contained pleomorphic clear vesicles of varying size, and the large majority of the synapses were of the symmetric type. Small ChAT-IR neurons were observed in all parts of the BL. Although the ChAT-IR cell bodies varied widely in shape from typical fusiform to round, most had a more or less oval shape with a major diameter of 10-14 micron. Most of the ChAT-IR neurons seemed to display a radial bipolar dendritic pattern, but multipolar cells were also observed. The ChAT-IR neurons contained an indented nucleus, which was often eccentrically located and surrounded by a thin or moderately thin rim of cytoplasm. The results obtained are discussed in relation to a quasi-cortical organization of the BL.

Amygdala↗

PubMed1986

Cholinergic and GABAergic afferents to the olfactory bulb in the rat with special emphasis on the projection neurons in the nucleus of the horizontal limb of the diagonal band.

We have examined the location of cholinergic and GABAergic neurons that project to the rat main olfactory bulb by combining choline acetyltransferase (ChAT) and glutamic acid decarboxylase (GAD) immunohistochemistry with retrograde fluorescent tracing. Since many of the projection neurons are located in subcortical basal forebrain structures, where the delineation of individual regions is difficult, particular care was taken to localize projection neurons with respect to such landmarks as the ventral pallidum (identified on the basis of GAD immunoreactivity), the diagonal band, and medial forebrain bundle. In addition, sections with fluorescent tracers or immunofluorescence were counterstained for Nissl substance in order to correlate tracer or immunopositive neurons with the cytoarchitecture of the basal forebrain. The majority of the cholinergic bulbopetal neurons are located in the medial half of the nucleus of the horizontal limb of the diagonal band (HDB), whereas only a few are located in its lateral half. A substantial number of cholinergic bulbopetal cells are also found in the sublenticular substantia innominata. A small number of cholinergic bulbopetal neurons, finally, are located in the ventrolateral portion of the nucleus of the vertical limb of the diagonal band. At the level of the crossing of the anterior commissure, approximately 17% of the bulbopetal neurons in the HDB are ChAT-positive. The noncholinergic bulbopetal cells are located mainly in the lateral half of the HDB. GAD-containing bulbopetal neurons are primarily located in the caudal part of the HDB, especially in its lateral part. About 30% of the bulbopetal projection neurons in the HDB are GAD-positive. A few GAD-positive bulbopetal cells, furthermore, are located in the ventral pallidum, anterior amygdaloid area, deep olfactory cortex, nucleus of the lateral olfactory tract, lateral hypothalamic area, and tuberomamillary nucleus. The topography of bulbopetal neurons was compared to other projection neurons in the HDB. After multiple injections of fluorescent tracer in the neocortex, retrogradely labeled neurons were concentrated in the most medial part of the HDB, while neurons projecting to the olfactory and entorhinal cortices were located in the ventral part of the HDB. These results show that the cells of the HDB can be divided into subpopulations based upon projection target as well as transmitter content. Furthermore, these subpopulations correspond, at least to a considerable extent, to areas that can be defined on cyto- and fibroarchitectural grounds.

Animals↗

PubMed1986

Distribution of GABAergic and cholinergic neurons in the rat diagonal band.

GABAergic neurons are coextensive with cholinergic neurons in the medial septum-diagonal band complex. Serial sectioning, sequential staining and double immunofluorescence techniques employing antibodies to glutamate decarboxylase and choline acetyltransferase revealed the distribution of these transmitter-specific neurons in the rat. Morphologically, the two types of neurons appear similar, in that they are predominantly large multipolar cells, but they are characterized by different, overlapping distributions in the diagonal band. Glutamate decarboxylase-positive cells are scattered throughout the nucleus of the vertical limb of the diagonal band, while choline acetyltransferase-positive neurons are more numerous medially and are distributed in groups corresponding to the dorsal and ventral aspects of the nucleus. In the rostral parts of the nucleus of the horizontal limb of the diagonal band, the choline acetyltransferase-positive cells tend to be located medially, whereas caudally they spread dorsal to the nucleus to become continuous with other large cholinergic neurons in the ventral pallidum and sublenticular substantia innominata. The large majority of glutamate decarboxylase-positive neurons remain in a more ventral and lateral position within the nucleus of the horizontal limb and are particularly numerous just lateral to the diagonal band fibers as they join the medial forebrain bundle. Cholinergic neurons were estimated to be about two times more numerous than GABAergic neurons. Approximately 1% of the choline acetyltransferase-positive neurons were also glutamate decarboxylase-positive in double immunofluorescence studies, but not in sequentially stained or serial sections.

Acetylcholine↗

PubMed1985

Synaptic contacts of ventral striatal cells in the olfactory tubercle of the rat: correlated light and electron microscopy of anterogradely transported Phaseolus vulgaris-leucoagglutinin.

Iontophoretic injections of the plant lectin Phaseolus vulgaris-leucoagglutinin (PHA-L) into the dense cell layer of the rat olfactory tubercle (OT) resulted in transport of the substance to the polymorph layer of the OT. Light microscopy revealed that the lectin was taken up in the superficial OT exclusively by medium-sized neurons with spiny dendrites of which the majority extended into the molecular layer. PHA-L-immunoreactive elements were observed in the adjoining part of the polymorph layer in the form of filaments and puncta which the electron microscope revealed to be axons and boutons forming symmetrical synaptic contacts, almost exclusively with typical pallidal-type dendrite profiles. The results reinforce the concept that the medium-size cells of the dense cell layer of the OT represent the ventral-most part of the striatum.

Animals↗

PubMed1985

Cholinergic projections from the basal forebrain to the basolateral amygdaloid complex: a combined retrograde fluorescent and immunohistochemical study.

We have examined the location of cholinergic and non-cholinergic neurons that project to the rat basolateral amygdaloid nucleus by using choline acetyltransferase (ChAT) immunohistochemistry in combination with retrograde fluorescent tracing on the same tissue section. Since many tracer-and ChAT-positive neurons were identified in basal forebrain areas, including the ventral pallidum, we also stained many of the sections for glutamate decarboxylase, a suitable marker for the delineation of pallidal areas. Cholinergic neurons projecting to the basolateral amygdaloid nucleus were observed in a continuous territory stretching from the dorsal part of ventral pallidum, through sublenticular substantia innominata to ventral parts of globus pallidus and peripallidal areas. Non-cholinergic neurons projecting to the basolateral amygdaloid nucleus were found intermixed within the same structures and constitute approximately 25% of the amygdalopetal projection neurons in these ventral forebrain structures. Since amygdalopetal cholinergic neurons were demonstrated in areas generally recognized as giving rise to cholinergic projections to cerebral cortex, several retrograde double-labeling experiments with two different fluorescent tracers were performed for the purpose of detecting the possible existence of collateral projections. The results obtained showed that the cholinergic basal forebrain neurons in general project to only one forebrain region, and, furthermore, that the cholinergic system consists of partially overlapping subsets of neurons that project to various neocortical and allocortical areas and to the amygdaloid body.

Amygdala↗

PubMed1985

Evidence for the coexistence of glutamate decarboxylase and Met-enkephalin immunoreactivities in axon terminals of rat ventral pallidum.

Evidence for the coexistence of glutamate decarboxylase (GAD) and Met-enkephalin (Met-Enk) in axon terminals of ventral pallidum was demonstrated by colocalization of anti-GAD and anti-Met-Enk immunoreactivities in alternate adjacent 1 micron serial sections. Conventional electron microscopy of immunostained ventral pallidum confirmed that the immunoreactive structures were boutons which made predominantly symmetrical synapses on ventral pallidal cell bodies and dendrites.

Animals↗

PubMed1985

Mapping of transmitter-specific connections: simultaneous demonstration of anterograde degeneration and changes in the immunostaining pattern induced by lesions.

This paper describes simple procedures which allow immunohistochemistry to be combined with a newly developed silver degeneration technique for the purpose of mapping transmitter-specific connections on the light microscopic level. Conditions of fixation, survival time and immunohistochemistry that contribute to optimal results are discussed.

Animals↗