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M M Mesulam

Publications and source records attributed to M M Mesulam.

At least 145 records · Page 8Linked to original sources
PubMed1986

A light and electron microscopic procedure for sequential double antigen localization using diaminobenzidine and benzidine dihydrochloride.

Very few double-antigen staining methods are available that are applicable to both light and electron microscopy. The objective of this study was to develop for localization of two neural antigens simultaneously a procedure which would be sensitive, simple to perform, offer permanent reaction products, and permit correlated light and ultrastructural analysis. The method employs sequential immunoperoxidase staining without antibody elution, in which the first sequence of antibodies is visualized with 3,3'-diaminobenzidine (DAB) and the second with benzidine dihydrochloride (BDHC). The DAB reaction product (brown and diffuse) was easily distinguishable from the BDHC deposit (blue, granular, and more electron-dense) by both light and electron microscopy. The procedure was used to simultaneously localize choline acetyltransferase-and either substance P or tyrosine hydroxylase in rat brain at both light and ultrastructural levels. Control experiments demonstrated the absence of both color mixing and antibody crossreactions, even when both primary antibodies were from the same species. This study demonstrates the usefulness of BDHC as a chromogen for immunoperoxidase staining either alone or in combination with DAB, and describes a double method which should have wide applicability for detailed studies of most pairs of antigens at both light and ultrastructural levels.

3,3'-Diaminobenzidine↗
PubMed1985

Cholinergic and non-cholinergic septohippocampal pathways.

Cholinergic innervation of the hippocampus was examined in the rat by immunocytochemical localization of choline acetyltransferase immunoreactivity combined with retrograde transport of horseradish peroxidase-conjugated wheatgerm agglutinin. It was found that at least 50% of hippocampal afferents arising in the septal-diagonal band region consisted of non-cholinergic projection neurons. In addition, scattered choline acetyltransferase-immunoreactive neurons were localized to the hippocampal formation. These results indicate that: (1) the septohippocampal pathway is neither uniformly nor predominantly cholinergic; and (2) confirm that cholinergic innervation of the hippocampal formation of the rat is derived in part from intrinsic neurons.

Acetylcholinesterase↗
PubMed1985

Reversible go-no go deficits in a case of frontal lobe tumor.

A 50-year-old woman had been treated for a psychiatric disorder for three years. Findings during the elementary neurological examination were essentially normal. However, a computed tomographic scan revealed a large meningioma in the falx involving the medial aspects of the frontal lobes bilaterally. Neuropsychological examination demonstrated deficits in complex attentional tasks and also many errors of commission in the go-no go test. Following surgical excision of the tumor, her go-no go performance became normal. This patient shows that damage to the medial frontal lobe can cause deficits in go-no go performance, and that these deficits can be reversible following resolution of the lesion.

Female↗
PubMed1985

Cortical afferent input to the principalis region of the rhesus monkey.

The sources of ipsilateral cortical afferent projections to regions along both banks of the principalis sulcus in the prefrontal cortex were studied with horseradish peroxidase in macaque monkeys. The principalis cortex receives a substantial proportion of its projections from neighboring prefrontal regions. However, differences were noted in the distribution of labeled cells projecting to the various principalis regions. These differences were most marked with respect to the relative proportion of cells originating in visual, auditory, somatosensory, premotor and limbic cortical areas. The findings indicate that the caudal ventral principalis region receives projections from both visual and visuomotor regions, whereas the anterior tip of the principalis appears to be the major target of projections from auditory association regions. The ventral bank at the middle extent of the principalis was the only case with a significant proportion of labeled cells in somatosensory association and premotor regions. There was a consistent increase in the proportion of labeled cells in limbic cortical areas projecting to more rostral principalis sites, irrespective of whether the injection was placed in the dorsal or ventral bank. These findings suggest that the caudal principalis region has a visual-visuomotor and the rostral, an auditory-limbic bias with respect to the long projections they receive.

Afferent Pathways↗
PubMed1984

Choline acetyltransferase-like immunoreactivity in the forebrain of the red-eared pond turtle (Pseudemys scripta elegans).

Choline acetyltransferase (ChAT) immunohistochemistry was used to map the cholinergic neurons in the forebrain of Pseudemys turtles. Cell bodies with ChAT-like immunoreactivity were seen in the septum, the nucleus of the diagonal band, and embedded within the medial and lateral forebrain bundles. The region of the medial and lateral forebrain bundles contained the greatest concentration of ChAT-positive neurons. Virtually no ChAT-like immunoreactivity was seen in the areas composing the reptilian homologue of the mammalian striatum. It is suggested that the turtle basal forebrain cholinergic neurons may represent the evolutionary precursors to the mammalian cholinergic neurons of the basal forebrain and even the striatum.

Acetylcholinesterase↗
PubMed1984

Regional variations in cortical cholinergic innervation: chemoarchitectonics of acetylcholinesterase-containing fibers in the macaque brain.

There are marked regional variations in the laminar distribution and intensity of acetylcholinesterase containing fibers in cortex. These fibers were particularly prominent in the 5 major paralimbic (mesocortical) regions of the brain: the insula, the caudal orbito-frontal cortex, the temporal pole, the cingulate gyrus and the parahippocampal region. Within these 5 areas, the part of cortex which is adjacent to allocortex has the most acetylcholinesterase and there is a gradual decline towards granular isocortex. The primary sensory-motor areas have distinctive laminar patterns of enzyme distribution. For example, primary visual, auditory and somesthetic konio-cortices are characterized by a salient band in layer IV. On the other hand, motor and premotor areas are characterized by a concentration of radially arranged fibers within the deeper layers of cortex. High order sensory association areas throughout the cortical mantle consistently contain the least amount of acetylcholinesterase-positive fibers. It is conceivable that these patterns reflect regional variations in the distribution of cortical cholinergic innervation. The cortical topography of cholinergic markers may be relevant to the biological organization of mood and memory and also to the pathophysiology of Alzheimer's disease and of partial epilepsy.

Acetylcholinesterase↗
PubMed1984

Thalamic connections of the insula in the rhesus monkey and comments on the paralimbic connectivity of the medial pulvinar nucleus.

Thalamic connections of the insula in the rhesus monkey were studied with axonal transport methods. Tritiated amino acid injections limited to the insula revealed autoradiographic label in the principal and parvicellular components of the ventroposterior medial nucleus, the ventroposterior inferior nucleus, the oral and medial pulvinar nuclei, the nucleus reuniens, the parvicellular and magnocellular components of the medial dorsal nucleus, the centromedian-parafasicularis nuclei, and the reticular nucleus. In additional animals, tritiated amino acids and horseradish perioxidase injections were made within different regions of the insula. Although the injection sites in these additional cases may have included minor extensions into claustrum and adjacent structures, several tentative conclusions emerged with respect to the antero-posterior gradient in insulothalamic connectivity. The anterior insula appears to have a more extensive relationship with the ventroposterior medial complex, the medial dorsal nucleus, the centromedian-parafasicularis nuclei and with some midline nuclei. In contrast, the posterior insula is more extensively connected with the ventroposterior inferior nucleus, the oral and medial pulvinar nuclei, and the suprageniculate nucleus. The patterns of insulothalamic connections support conclusions derived from observations on the cortical connectivity of the primate insular cortex indicating that the anterior insula is related to olfactory, gustatory, and viscero-autonomic behavior, whereas the posterior insula is related to auditory-somesthetic-skeletomotor function (Mesulam and Mufson, '82b). The medial pulvinar nucleus has extensive connections with many paralimbic cortical regions including the insula as well as with high order polymodal association cortex. These findings suggest that the medial pulvinar may provide a region for the convergence of multisensory association input with limbic information.

Animals↗
PubMed1984

Cortical projections arising from the basal forebrain: a study of cholinergic and noncholinergic components employing combined retrograde tracing and immunohistochemical localization of choline acetyltransferase.

The neurochemical identity of ascending putative cholinergic pathways from the rat basal forebrain was investigated employing a method for simultaneously visualizing choline acetyltransferase immunoreactivity and retrogradely transported horseradish peroxidase-conjugated wheatgerm agglutinin. This histochemical procedure revealed three distinct populations of neurons: (1) cells which stained only for choline acetyltransferase immunoreactivity; (2) cells which stained only for retrograde tracer and (3) cells which stained simultaneously for choline acetyltransferase immunoreactivity and retrograde tracer. The results demonstrated that this projection is topographically organized and consists of both cholinergic and noncholinergic components. The relative contribution of each component varied with the telencephalic target area as follows: the olfactory bulb receives a projection from cells of the horizontal limb nucleus, 10-20% of which are cholinergic (Ch3); the hippocampal formation receives afferents from cells of the medial septal and vertical limb nuclei, 35-45% of which are cholinergic (Ch1 and Ch2); and the cortical mantle receives afferents primarily from cells within the substantia innominata-nucleus basalis complex, 80-90% of which are cholinergic (Ch4). The topographical organization of Ch4 projections is not as completely differentiated as we have previously observed in the primate.

Animals↗
PubMed1984

Atlas of cholinergic neurons in the forebrain and upper brainstem of the macaque based on monoclonal choline acetyltransferase immunohistochemistry and acetylcholinesterase histochemistry.

Choline acetyltransferase immunohistochemistry was used to map the cholinergic cell bodies in the forebrain and upper brainstem of the macaque brain. Neurons with choline acetyltransferase-like immunoreactivity were seen in the striatal complex, in the septal area, in the diagonal band region, in the substantia innominata, in the medial habenula, in the pontomecencephalic tegmentum and in the oculomotor and trochlear nuclei. The ventral striatum contained a higher density of cholinergic cell bodies than the dorsal striatum. All of the structures that contained the choline acetyltransferase positive neurons also had acetylcholinesterase-rich neurons. Choline acetyltransferase positive neurons were not encountered in the cortex. Some perikarya in the midline, intralaminar, reticular and limbic thalamic nuclei as well as in the hypothalamus were rich in acetylcholinesterase but did not give a positive choline acetyltransferase reaction. A similar dissociation was observed in the substantia nigra, the raphe nuclei and the nucleus locus coeruleus where acetylcholinesterase-rich neurons appeared to lack perikaryal choline acetyltransferase activity.

Acetylcholinesterase↗
PubMed1984

Choline acetyltransferase-immunoreactive neurons intrinsic to rodent cortex and distinction from acetylcholinesterase-positive neurons.

Cholinergic neurons intrinsic to rat cortex were studied using a sensitive method for the localization of choline acetyltransferase immunoreactivity, acetylcholinesterase histochemistry, combined localization of choline acetyltransferase and acetylcholinesterase, and combined localization of choline acetyltransferase and retrogradely transported horseradish peroxidase-wheat germ agglutinin. Choline acetyltransferase immunoreactivity was localized predominantly in small bipolar cortical neurons within the upper layers of isocortex, while small multipolar neurons were the predominantly stained cell type in allocortical regions. Acetylcholinesterase histochemistry demonstrated mainly small polymorphic cells scattered throughout all cellular layers in all cortices. Combined staining for choline acetyltransferase and acetylcholinesterase resulted in localization of the markers in different cell populations; choline acetyltransferase-immunoreactive neurons did not contain detectable acetylcholinesterase and acetylcholinesterase-positive neurons did not contain detectable immunoreactivity to choline acetyltransferase. Some possible connections of the cortical choline acetyltransferase-immunoreactive cells were studied in rats which had received injections of horseradish peroxidase-wheat germ agglutinin into either cortex or brainstem. The choline acetyltransferase-immunoreactive cells were frequently admixed with cells labeled with the retrograde marker; however, no double-labeled cells were observed. It was concluded that cortical cholinergic cells are not visualized by acetylcholinesterase histochemistry, and are likely to be involved in local circuitry.

Acetylcholinesterase↗
PubMed1984

Neural inputs into the nucleus basalis of the substantia innominata (Ch4) in the rhesus monkey.

Neurons of the nucleus basalis-substantia innominata-nucleus of the ansa peduncularis complex (Ch4) provide the major source of cholinergic innervation for the entire neocortical surface. In contrast to their widespread projections to all parts of the neocortex, these neurons receive reciprocal projections from only very few cortical areas. Most of the sensory, motor, and association areas in the frontal, parietal, occipital and temporal lobes do not seem to project back to the Ch4 complex. The Ch4 neurons receive their cortical input from prepyriform cortex, orbitofrontal cortex, the anterior insula, the temporal pole, entorhinal cortex and the medial temporal cortex. There are also subcortical inputs from septal nuclei, the nucleus accumbens-ventral pallidum complex and the hypothalamus. This organization suggests that the Ch4 complex is in a position to act as a cholinergic relay for transmitting predominantly limbic and paralimbic information to the neocortical surface. It would also appear that the cortical areas which do not project into Ch4 have no direct way of controlling the cholinergic input which they receive, whereas the limited set of cortical areas which do project into Ch4 can control not only the cholinergic innervation that they receive but also the cholinergic innervation into the entire neocortical mantle.

Alzheimer Disease↗
PubMed1983

Developmental learning disabilities of the right hemisphere. Emotional, interpersonal, and cognitive components.

In 14 patients, we encountered a behavioral syndrome that begins in early life and is characterized by emotional and interpersonal difficulties, shyness, visuospatial disturbances, and inadequate paralinguistic communicative abilities. All 14 patients had at least average intellectual capacity, but each had demonstrated some academic failure, particularly in arithmetic. Examination revealed neurologic and neuropsychological signs consistent with right-hemisphere dysfunction. Most of the patients avoided eye contact and lacked the gestures and prosody that normally accompany and accentuate speech. Although many of them could not convey their feelings, there was no evidence that they were unable to experience affect. Eight of them reported a family history of similar symptoms. Just as developmental involvement of the left hemisphere may produce dyslexia, damage to the right hemisphere suffered early in life, or inherited, may lead to chronic emotional difficulties, a disturbance of interpersonal skills, and poor visuospatial ability.

Achievement↗
PubMed1983

Co-localization of acetylcholinesterase and choline acetyltransferase in the rat cerebrum.

Acetylcholinesterase-histochemistry has been widely used for localizing cholinergic neurons despite specificity problems. The distribution of cells stained with this method has never been directly compared on a histochemical level with the specific cholinergic marker, choline acetyltransferase. We recently reported the immunohistochemical localization of choline acetyltransferase using monoclonal antibodies [Levey A. I., Armstrong D., Atweh S. F., Terry R. D. & Wainer B. H. (1983) J. Neurosci 3, 1-9]. Here we report the development of a combined histochemical and immunohistochemical method for the co-localization of the 2 cholinergic markers, and their comparison in the rat cerebrum. Although the precise relationship between the markers was complex, the important results were: (1) all neurons which contained choline acetyltransferase also contained some acetylcholinesterase; (2) many acetylcholinesterase-containing neurons did not contain any demonstrable choline acetyltransferase; (3) all neurons which stained intensely for acetylcholinesterase in the neostriatum and basal forebrain also contained choline acetyltransferase; and (4) many choline acetyltransferase-containing neurons did not stain intensely for acetylcholinesterase. The results corroborate the assumption that choline acetyltransferase is a more specific marker for cholinergic neurons than acetylcholinesterase. Intense staining for acetylcholinesterase can be reliably used in some regions of the cerebrum for identifying cholinergic neurons, however, it should be recognized that this criterion s not essential for all cholinergic neurons.

Acetylcholinesterase↗