Search PubMed⌕ Search

Biomedical subjects

L L Butcher

Publications and source records attributed to L L Butcher.

At least 55 records · Page 3Linked to original sources

Developing cholinergic basal forebrain neurons are sensitive to thyroid hormone.

The influence of thyroid hormone on the development of cholinergic neurons in nucleus basalis was assessed in hyperthyroid, hypothyroid, and euthyroid rats by use of CAT immunohistochemistry and single-section Golgi-impregnation histology. Animals were made either hyperthyroid by daily injections of 1.0 micrograms/gm body weight triiodothyronine starting at postnatal day (P) 3 or hypothyroid by providing 0.4% propylthiouracil in the diet of dams from P2. Compared to developing control rats, increased exposure to thyroid hormone resulted in accelerated expression of CAT in nucleus basalis neurons. Overshoot in cell body size, a normal developmental phenomenon of cholinergic neurons in the basal nuclear complex, occurred earlier in hyperthyroid brains and was of a greater magnitude than in controls. Furthermore, increased numbers of primary dendrites and dendritic branchpoints accompanied by dendritic and perisomal filopodia-like structures were observed for nucleus basalis neurons in hyperthyroid rats. These dendritic changes persisted throughout the second postnatal month. After the fifth postnatal week, cell body sizes of these hyperthyroid CAT-positive neurons began to decrease and by P50 were significantly less than controls or similarly treated animals at earlier ages. By P64, the number of cholinergic neurons in nucleus basalis was appreciably less than in age-matched controls. Hypothyroidism resulted in a delay of normal CAT expression that persisted throughout the third postnatal week. After this time, CAT staining increased until normal immunoreactivity was attained in cell bodies, fibers, and terminal regions by P35. A deficit in thyroid hormone during development prevented overshoot in perikaryal size and resulted in diminished cross-sectional areas throughout the cholinergic nucleus basalis at all ages examined. Hypothyroidism also prevented the normal overproduction of dendrites in those cells and produced stunted dendritic trees at all ages examined. These morphological abnormalities persisted throughout the second postnatal month. The effects of thyroid hormone on cholinergic projection neurons in the rat brain appeared relatively selective for cells in the basal nuclear complex because neither hypothyroid nor hyperthyroid treatment produced changes in the cell body areas of the phenotypically similar CAT-positive neurons of the pontomesencephalotegmental complex.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Feline islands of Calleja complex: I. Cytoarchitectural organization and comparative anatomy.

Cytoarchitectural analyses demonstrated that the islands of Calleja complex (ICC) is highly developed and discretely organized in the cat. The feline complex is clearly divided into morphological units, each containing a granular Callejal island and a population of satellite neurons. These ICC units change progressively in cytoarchitecture from the lateral to the medial edge of the olfactory tubercle. In particular, the islands flatten, sink into the tubercular molecular layer, and increase in cell density, while their satellite neurons increase in number and decrease in size. The lateromedial transformation was judged to take place in five stages, resulting in the successive appearance of lateral, lateral transitional, central, medial transitional, and medial ICC units. The first two unit types display prominently two additional components of the feline ICC-namely, clusters of dwarf cells and small pyramidal-like neurons constituting the densocellular layer cupping the base of lateral Callejal islands. All of the various types of ICC units contact the tubercular molecular layer via their dwarf and/or granule cell components, raising the possibility of direct olfactory input to the entire Callejal complex (apart from the isla magna). Output from the complex is presumed to arise from the satellite neurons, which are distinguished from adjoining cell populations by their close association with Callejal islands, typical chromophilic character, and relatively large size (15-42 micron in soma length). In the tubercular ICC, these neurons are most numerous immediately above Callejal islands in a fiber-rich zone continuous with the supratubercular zone and hence with the ventral pallidum. In the accumbal ICC, satellite neurons are most conspicuous in granule-cell-poor spaces within the isla magna, where many non-granular neurons are uncharacteristically small and chromophobic. The isla magna itself is unusual not only for its large size but for lateral extensions encircling a group of accumbal neurons far caudally. Such extensions are one of several indications that the isla magna is intimately associated with the nucleus accumbens. A comparative anatomical survey of the ICC in rats, cats, and macaque monkeys demonstrated a number of species differences. Of particular interest is the finding that the complex is unambiguously divided into discrete island-satellite cell units only in cats and macaques. In these species, the complex is also distinguished by a predominance of superficial islands and an especially prominent isla magna. ICC units, however, were most conspicuous in cats.

Animals↗

Feline islands of Calleja complex: II. Cholinergic and cholinesterasic features.

Histochemical analyses demonstrated that the islands of Calleja complex (ICC) in the cat is exceptionally rich in choline acetyltransferase (ChAT) and acetylcholinesterase (AChE). Both enzymes are found in neuropil throughout the complex, as well as in a subset of the satellite neurons accompanying Callejal islands. Lateromedial changes in these cholinergic and cholinesterasic tissue elements were consistent with our previous finding that the feline ICC is cytoarchitecturally divided into five successively more medial types of island-satellite cell ensembles or units. In particular, satellite neurons reactive for ChAT and AChE diminished progressively in size and increased steadily in number from the most lateral to the most medial units. A concomitant increase in neuropil levels of both enzymes suggested that the strong cholinergic innervation of the feline ICC is at least partially derived from satellite cells. This possibility gained further credibility from the additional observation that very fine processes from some ChAT and AChE satellite neurons projected into the terminal-like cholinergic field permeating the granular Callejal islands. The granule cells themselves lacked ChAT and (apart from potentially artifactual cases) AChE, as did adjoining groups of dwarf cells and small pyramidal like neurons. The cholinergic and cholinesterasic satellite neurons were preferentially located above tubercular Callejal islands and in otherwise cell-poor spaces within the isla magna. Such neurons appeared to be isodendritic: they commonly had ovoidal somata with one or two processes lacking enzyme-reactive spines. Depending on the type of ICC unit involved, their mean soma length ranged from 15 to 24 micron, all but the largest of which was distinctly smaller than that of ChAT and AChE cells in striatal or basal nuclear structures. Not all the cholinesterase neurons in the feline ICC are cholinergic, judging from the finding that there are a significantly greater number of satellite neurons containing AChE than ChAT. Three cholinergic features of the feline ICC are especially noteworthy. First, each of the island-satellite cell ensembles in the complex is unified by AChE neuropil often denser than that of adjacent striatal areas. Second, cholinergic neuropil is exceptionally dense in the isla magna and in a subpial band under medial Callejal islands. Third, ChAT neurons in the isla magna are among the smallest cholinergic cells found in the brain.

Acetylcholinesterase↗

'Cat P300' disappears after septal lesions.

Endogenous responses were recorded from 9 awake cats with loud and soft clicks randomly presented as rare (P = 0.15) or frequent (P = 0.80) stimuli; a reinforced tone CS (P = 0.05) resulted in a conditioned eye blink response and focused the cat's attention on the auditory stimuli. Subsequent to 12 preoperative recording sessions the medial septal area was lesioned in 7 cats and similar but more rostral lesions were placed in 2 cats. Thereafter, 12 postoperative recording sessions were carried out, the animals were terminated, and the brains processed for AChE histochemistry and histology of the lesioned areas. Destruction of the medial septum and vertical limb of the diagonal band of Broca resulted in a transient postoperative 'cat P300' followed by reduction and disappearance of the response. The hippocampus of these animals was characterized by marked AChE depletion. In contrast, the animals with lesions rostral to the medial septal area showed no postoperative change in the P300 response and no depletion of hippocampal AChE. These data indicate an important role for the medial septal area as a modulator of 'cat P300' generation possibly through the cholinergic component of the septohippocampal projection system.

Acetylcholinesterase↗

Cholinergic-dopaminergic interactions in radial-arm maze performance.

Although acetylcholine and dopamine are believed to play complementary roles in motor function, a comparable neurochemical interaction has not been established for cognitive function. The muscarinic receptor blocker scopolamine and the dopaminergic antagonist haloperidol have been found to impair choice accuracy of rats in the radial-arm maze. In the present study, low doses of these two drugs were administered intraperitoneally either alone or in combination to rats trained on a working memory task (food reward) in an eight-arm radial maze. Scopolamine, 0.125 mg/kg, produced a significant decrease in choice accuracy (i.e., arm entries until an error). Haloperidol, 0.0625 mg/kg, did not cause a significant decrease in accuracy, but there was a trend in that direction. The combination of haloperidol with scopolamine attenuated significantly the amnestic effect of scopolamine. These results suggest that, like motor behavior, cognitive function may be influenced by the balance between acetylcholine and dopamine.

Acetylcholine↗

Transient expression of choline acetyltransferase-like immunoreactivity in Purkinje cells of the developing rat cerebellum.

The expression of choline acetyltransferase (ChAT)-like immunoreactivity was studied immunohistochemically in the cerebelli of developing rats. Brains were examined from the day of birth (postnatal day 1: P1) until adulthood. From P4 through P21, several Purkinje cells in the uvula, nodule, and flocculus of the cerebellum demonstrated ChAT-like immunoreactivity. After P23, no ChAT-positive neurons were observed in any region of the cerebellum. This finding paralleled the transient expression of acetylcholinesterase in Purkinje cells of these same cerebellar areas during development.

Acetylcholinesterase↗

Is ethylcholine mustard aziridinium ion a specific cholinergic neurotoxin?

The histopathologic effects of different doses of ethylcholine mustard aziridinium ion infused into the caudate-putamen complex or nucleus basalis were evaluated in rats. Although no non-specific tissue damage was observed at the lowest doses of ethylcholine mustard aziridinium ion examined--0.01 nmol in 1-microliter vehicle and 0.02 nmol in 2-, 5-, and 10-microliters vehicle in both the striatum and nucleus basalis--minimal but definite non-selective pathology, characterized by gliosis and loss of all neuronal elements in the region affected by the nitrogen mustard, was observed in both targets at a dose of 0.02 nmol 1 microliter and more severely at all doses containing 0.05 and 0.1 nmol ethylcholine mustard aziridinium ion. At doses of ethylcholine mustard aziridinium ion containing 0.2 nmol of the cytotoxin and greater amounts, non-specific cell loss in intact tissue and extensive cavitation became increasingly the most prominent histologic features of drug action. No statistically significant effects of ethylcholine mustard aziridinium ion on striatal choline acetyltransferase activities were found until doses of 0.4 nmol/1 microliter or greater were injected, concentrations of the cytotoxin at which appreciable non-specific pathology was also observed. Levels of dopamine in the caudate-putamen nucleus were reduced by comparatively greater amounts than choline acetyltransferase at doses of 2.5 nmol/2 microliters, 5.0 nmol/2 microliters and 10 nmol/2 microliters cytotoxin, but a significant effect of ethylcholine mustard aziridinium ion on striatal L-glutamate decarboxylase activity was found only at a dose of 10 nmol/2 microliters. As no dose of ethylcholine mustard aziridinium ion was found that reduced choline acetyltransferase without producing considerable non-specific tissue destruction, the usefulness of the cytotoxin in studying the behavioral and physiological consequences of selective cholinergic hypofunction in the brain must be questioned.

Animals↗

Cholinergic and non-cholinergic projections from the rat basal forebrain revealed by combined choline acetyltransferase and Phaseolus vulgaris leucoagglutinin immunohistochemistry.

A two-color fluorescence method is described for demonstrating immunohistochemically the anterogradely transported plant lectin Phaseolus vulgaris leucoagglutinin (PHAL, fluorescein isothiocyanate label) and choline acetyltransferase (ChAT, rhodamine label) on the same rat brain section. Application of this method to the study of projection neurons in the vertical and horizontal limbs of the diagonal band, the substantia innominata and nucleus basalis revealed that both cholinergic and non-cholinergic pathways followed similar trajectories to their targets. These included: projections from the vertical, and, to a lesser extent, horizontal limb of the diagonal band coursing through the dorsal fornix, alveus and fimbria to the hippocampus; fibers from the vertical and horizontal limbs of the diagonal band traveling anteriorly to the anterior olfactory nucleus, posterolaterally to the entorhinal cortex, and anterodorsally into the cingulum to the cingulate and retrosplenial, and, in some cases, the frontal and occipital cortices; projections, mostly non-cholinergic, from the substantia innominata traveling laterally to the piriform cortex and amygdala, and anteriorly to the anterior olfactory nucleus and olfactory bulb; and fibers from cells in the nucleus basalis coursing dorsally to the frontal and parietal cortices or laterally to the basolateral amygdala and piriform, insular and temporal cortices. Some axon terminations ended at right angles to the parent axon shaft in short protuberances resembling terminal boutons.

Animals↗

Cholinergic neurons in the rat substantia nigra.

The distribution of choline acetyltransferase (ChAT)-like immunoreactivity (LI), demonstrated according to an avidin-biotin procedure, was evaluated in the substantia nigra (SN) of rats. Although ChAT positivity was considerably less in the nigral neuropil than in the interpeduncular nucleus, it was also higher, particularly in caudal pars reticulata, than background as exampled by ChAT staining in the mesencephalic tegmentum, medial lemniscus and cerebral peduncle. Unexpectedly, a few ChAT-containing cells (approximately 1-5 per brain section) were also observed within the borders of pars reticulata of the substantia nigra but only at caudal levels. These latter cells were large (20-30 microns in maximum soma extent) and were morphologically similar to ChAT-positive neurons in, for example, the laterodorsal tegmental nucleus and substantia innominata. Although the origins of ChAT-LI in the nigral neuropil are unknown, possible sources include the processes of intranigral ChAT-containing cells, as well as extranigral cholinergic neurons. It is suggested that the ChAT-positive cells in the SN may be ectopically located neurons of the pontomesencephalotegmental cholinergic system.

Animals↗

Cholinergic systems in the rat brain: III. Projections from the pontomesencephalic tegmentum to the thalamus, tectum, basal ganglia, and basal forebrain.

The ascending cholinergic projections of the pedunculopontine and dorsolateral tegmental nuclei, referred to collectively as the pontomesencephalotegmental (PMT) cholinergic complex, were investigated by use of fluorescent tracer histology in combination with choline-O-acetyltransferase (ChAT) immunohistochemistry and acetylcholinesterase (AChE) pharmacohistochemistry. Propidium iodide, true blue, or Evans blue was infused into the anterior, reticular, mediodorsal, central medial, and posterior nuclear areas of the thalamus; the habenula; lateral geniculate; superior colliculus; pretectal/parafascicular area; subthalamic nucleus; caudate-putamen complex; globus pallidus; entopeduncular nucleus; substantia nigra; medial septal nucleus/vertical limb of the diagonal band area; magnocellular preoptic/ventral pallidal area; and lateral hypothalamus. In some animals, separate injections of propidium iodide and true blue were made into two different regions in the same rat brain, usually a dorsal and a ventral target, in order to assess collateralization patterns. Retrogradely transported fluorescent labels and ChAT and/or AChE were analyzed microscopically on the same brain section. All of the above-delimited targets were found to receive cholinergic input from the PMT cholinergic complex, but some regions were preferentially innervated by either the pedunculopontine or dorsolateral tegmental nucleus. The former subdivision of the PMT cholinergic complex projected selectively to extrapyramidal structures and the superior colliculus, whereas the dorsolateral tegmental nucleus was observed to provide cholinergic input preferentially to anterior thalamic regions and rostral portions of the basal forebrain. The PMT cholinergic neurons showed a tendency to collateralize extensively.

Acetylcholine↗

Plaque-like lesions in the basal forebrain in Alzheimer's disease.

Silver staining (Bodian procedure) in the nucleus of the sublenticular substantia innominata (SI), also referred to as the nucleus basalis of Meynert, was evaluated in autopsy material from patients with Alzheimer's disease or senile dementia of the Alzheimer type (age at death: mean 69 years, range 63 to 81 years; time between onset of symptoms and death: mean 5.6 years, range 2.5 to 11.0 years). Although a decrease in the number of neurons and an increase in gliosis were observed in the SI in the Alzheimer dementia cases, classic senile plaques, as well as neurofibrillary tangles and granulovacuolar degeneration, were, with rare exception, not present in the basal forebrain. Small plaque-like lesions, 30-50 micron in diameter, were found scattered throughout the SI, however. These pathologic entities, like traditional senile plaques, demonstrated increased argentophilia compared to background, neuritic elements, and an increase in the number of glial cells. The magnitude of silver staining in the plaque-like lesions in the SI, however, was generally less than that associated with plaques in the cortex, hippocampus and amygdala. Although their significance is not known, plaque-like structures in the SI could represent the final degenerative phases of basal forebrain neurons and/or of fibers afferent to them. Their precise relationship to classic senile plaques remains to be elucidated.

Adolescent↗

Alzheimer dementia and reduced nicotinamide adenine dinucleotide (NADH)-diaphorase activity in senile plaques and the basal forebrain.

The activity of reduced nicotinamide adenine dinucleotide (NADH)-diaphorase was examined histochemically in the amygdala, cortex and sublenticular substantia innominata (nucleus basalis of Meynert) of patients with Alzheimer's disease and senile dementia of the Alzheimer type (SDAT). Senile plaques were characterized by increased enzyme levels and the presence of astrocytes highly reactive for NADH-diaphorase. In the sublenticular substantia innominata, the number of neurons positive for NADH-diaphorase was reduced in both Alzheimer's disease and SDAT, a result paralleled by a reduction of Nissl-stained cells, and this pathology was accompanied by an increase in the number of astrocytes. Intact substantia innominata somata in the former dementia, however, showed essentially normal levels of the enzyme, whereas in the SDAT patients, an abnormal distribution of NADH-diaphorase was observed frequently. It is proposed that the increased NADH-diaphorase associated with senile plaques and their accompanying astrocytes may be linked, in part, to the increased astrogliosis and decrease of neurons in the basal forebrain and that neuropathologic differences may exist between Alzheimer's disease and SDAT in terms of energy metabolism.

Aged↗

Cholinergic systems in the rat brain: II. Projections to the interpeduncular nucleus.

The cholinergic innervation of the interpeduncular nucleus was investigated by use of fluorescent tracer histology in combination with choline-O-acetyltransferase (ChAT) immunohistochemistry and acetylcholinesterase (AChE) pharmacohistochemistry. Following propidium iodide or Evans Blue infusion into the interpeduncular nucleus, brains were processed for co-localization of transported fluorescent label and ChAT and AChE. Control infusions of tracers were made into the ventral tegmental area. In order to delimit the course of putative cholinergic afferents to the interpeduncular nucleus from extra-habenular sources, knife cuts surrounding the habenular nuclei were performed. Somata containing propidium iodide that were highly immunoreactive for ChAT were found primarily in the vertical and horizontal limbs of the diagonal band, the magnocellular preoptic area, and the dorsolateral tegmental nucleus, also referred to as the laterodorsal tegmental nucleus. A few such co-labeled somata were also detected in the medial septal nucleus, substantia innominata, nucleus basalis, and pedunculopontine tegmental nucleus. A good correlation was observed between intensely-staining, AChE-containing and ChAT-positive neurons projecting to the interpeduncular nucleus from the aforementioned structures. Although the medial habenula contained numerous cells demonstrating transported label following interpeduncular infusion of fluorescent tracers, the ChAT-positivity associated with somata in that nucleus was weak compared to ChAT-like immunoreactivity in known cholinergic neurons in the basal forebrain and brainstem. Knife cuts that separated the habenular nuclei from the stria medullaris and neural regions lateral and posterior to those nuclei while leaving the fasciculus retroflexus intact resulted in a reduction of ChAT-like immunoreactivity in the medial habenular nucleus, fasciculus retroflexus, and interpeduncular nucleus. These data suggest (1) that the cholinergic innervation of the interpeduncular nucleus derives primarily from ChAT-positive cells in the basal forebrain and dorsolateral tegmental nucleus and (2) that putative cholinergic fibers having their origin in the medial habenula, if they exist, constitute a minor portion of the cholinergic input to the interpeduncular nucleus.

Acetylcholinesterase↗

Evidence that efferents from the basolateral amygdala innervate the dorsolateral neostriatum in rats.

The dorsolateral precommissural caudate-putamen complex has been characterized recently as a 'non-limbic' region of the neostriatum. In the present study, however, it was found that numerous neurons in the basolateral amygdala were labeled retrogradely following infusions of Evans Blue into that neostriatal region. Control infusions demonstrated that such labeling could not be attributed to the spread of the red fluorescent tracer into surrounding neocortical areas. On the basis of these data, it is proposed that: (1) the amygdalo-neostriatal pathway may be more extensive than previously believed, and (2) the basolateral amygdala may serve as an important link between the limbic and extrapyramidal motor systems.

Acetylcholinesterase↗

Guanethidine sympathectomy does not prevent meal-induced increases in the weight or oxygen consumption of brown fat.

The interscapular brown adipose tissue (BAT) of adult rats that were neonatally sympathectomized with guanethidine (GUA) consumed less oxygen but weighed the same as BAT from intact controls. In response to a 2-hr mixed-constituent meal, BAT from sympathectomized and control rats showed similar increases in oxygen uptake and weight. These data suggest that some functions of BAT can be maintained even without sympathetic stimulation.

Adipose Tissue, Brown↗

Cholinergic systems in the rat brain: I. projections to the limbic telencephalon.

The cholinergic projections to the limbic telecephalon in the rat were investigated by use of fluorescent tracer histology in combination with choline-O-acetyltransferase (ChAT) immunohistochemistry and acetylcholinesterase (AChE) histochemistry (pharmacohistochemical regimen). Propidium iodide or Evans Blue was infused into the olfactory bulb, hippocampus, dorsal retrohippocampal region, amygdala, and the entorhinal, perirhinal, pyriform, insular, and cingular cortices. Retrogradely transported fluorescent labels and ChAT and/or AChE were microscopically analyzed on the same brain section. Virtually all of the cholinergic projections to the limbic telencephalon derived from the basal forebrain cholinergic system composed of neurons associated with the medial septal nucleus, nuclei of the vertical and horizontal limbs of the diagonal band, the magnocellular preoptic area, the subpallidal substantia innominata and its rostral extension into the regions of the ventral pallidum laterally and the lateral preoptic area medially, and the nucleus basalis. The cingulate cortex received a small cholinergic projection from the dorsolateral tegmental nucleus in the brainstem. All of the presumed cholinergic innervation of the olfactory bulb, hippocampus, and dorsal retrohippocampal area and the majority of cholinergic afferents to posterior cingulate and entorhinal cortices derived from the medial septal nucleus, vertical and horizontal limbs of the diagonal band, magnocellular preoptic area, and rostral substantia innominata. Putative cholinergic afferents to the amygdala and to pyriform, insular, perirhinal, and anterior cingulate cortices orginated from ChAT-positive cells concentrated more caudally in the basal forebrain cholinergic system. Within the basal forebrain, no simple topographic pattern emerged to explain the cholinergic innervation of the limbic telencephalon, although an essentially reverse rostrocaudal organization was observed for afferents to the cingular region. It was noted, however, that most regions of the limbic telencephalon received cholinergic input from rostral portions of the basal forebrain cholinergic system, an observation inviting speculation that anterior aspects of the basal forebrain provide cholinergic afferents primarily to limbic structures in the telencephalon whereas more caudal portions are the source of cholinergic fibers preferentially innervating non-limbic regions. Of the total number of projection neurons innervating a given region of the limbic telencephalon, a greater proportion was ChAT-positive if phylogenetically newer target structures were innervated.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholinesterase↗

Influence of sympathectomy on the lateral hypothalamic lesion syndrome.

Sympathetic involvement in the lateral hypothalamic (LH) lesion syndrome was examined. Male rats were surgically or chemically sympathectomized and then given LH lesions. At 24 hr postlesion, lesion-induced hyperglycemia but not hyperthermia was attenuated by splanchnicectomy and celiac ganglionectomy. Hyperthermia but not hyperglycemia was attenuated by adrenal demedullation, adrenalectomy, and neonatal guanethidine treatment. Guanethidine-sympathectomized rats also displayed lower basal temperatures, more perilesion chromatolysis, and severer external symptoms than their controls. No form of sympathectomy affected lesion-induced gastric pathology, plasma gastrin concentrations, or body weight loss. Nor did any sympathectomy influence the recovery of ingestive behavior, daily food intake, the feeding response to 2-deoxy-D-glucose, or body weight maintenance in recovered LH-lesion subjects. These results suggest that sympathetic hyperactivity contributes to some aspects of the acute LH syndrome: Hyperglycemia results from sympathetic outflow to the abdomen, whereas hyperthermia is determined by circulating catecholamines and extraabdominal sympathetic innervation. The results fail to support the hypothesis that chronic increases in sympathetic tone are responsible for the reduced food intake and body weight of the LH-lesion rat.

Animals↗

Cholinergic projections from the basal forebrain to the frontal cortex: a combined fluorescent tracer and immunohistochemical analysis in the rat.

Cholinergic projections from the basal forebrain to some regions of the frontal cortex were studied by infusing propidium iodide (PI), a fluorescent tracer, into areas 6 and 10 and microscopically assessing the cellular co-localization of PI and immunohistochemically demonstrated choline-O-acetyltransferase (ChAT). The same brain sections were additionally processed for acetylcholinesterase (AChE, pharmacohistochemical regimen) and Nissl material (cresyl violet stain). Basal forebrain neurons projecting to the frontal cortex were found primarily in nucleus basalis, but others were located in association with the substantia innominata/lateral preoptic area, magnocellular preoptic area, and ansa lenticularis. These projection neurons were large (greater than 25 micrometers in maximum soma extent), demonstrated ChAT-like immunoreactivity, stained intensely for AChE following systemic administration of bis-(1-methylethyl)phosphorofluoridate, and were highly chromophilic.

Acetylcholinesterase↗