Cholinergic systems in mammalian brain and spinal cord.
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Acetylcholine↗
Biomedical subjects
N J Woolf
Publications and source records attributed to N J Woolf.
Postnatal development of cholinergic neurons in the rat: I. Forebrain.
The postnatal development of cholinergic projection and local-circuit neurons in the rat forebrain was examined by use of choline acetyltransferase (ChAT) immunohistochemistry and acetylcholinesterase (AChE) histochemistry. Although regional nuances were apparent, a general trend emerged in which cholinergic projection neurons in the basal nuclear complex (i.e., medial septal nucleus, vertical and horizontal diagonal band nuclei, magnocellular preoptic field, substantia innominata, nucleus basalis, and nucleus of the ansa lenticularis) demonstrated ChAT-like immunoreactivity earlier in postnatal development than intrinsically organized cholinergic cells in the caudate-putamen nucleus and nucleus accumbens, although this disparity was less apparent for local circuit neurons in the olfactory tubercle and Islands of Calleja complex. Ontologic gradients of enzyme expression also existed in some regions. A lateral to medial progression of ChAT and AChE appearance was observed as a function of increasing postnatal age in the nucleus accumbens and rostral caudate-putamen nucleus. By comparison, a rostrocaudal gradient of expression of ChAT-like immunoreactivity was apparent within the basal nuclear complex. Moderate to intense ChAT positivity, for example, appeared first in the medial septal nucleus. Furthermore, compared to more caudal regions, a greater proportion of AChE-positive neurons in rostral aspects of the basal forebrain expressed ChAT immunoreactivity on postnatal day 1, a difference that was no longer present by postnatal day 5. Cholinergic neurons in all forebrain regions also underwent an initial stage of progressive soma and proximal-dendrite hypertrophy, which peaked during the third postnatal week, followed by a period of cell-body and dendritic shrinkage that persisted into the fifth postnatal week when adult configurations were reached. These soma and dendritic size increases and decreases were not correlated with the magnitude of postnatal ChAT expression, which increased progressively until adult levels were attained approximately by the third to fifth weeks after birth. Expression of AChE in putative cholinergic neurons appeared to precede that of ChAT, especially in the caudate-putamen complex. Staining intensity of AChE also incremented earlier than that of ChAT.
Animals↗
Cholinergic neurons of the feline pontomesencephalon. I. Essential role in 'Wave A' generation.
Wave A in the cat appears to be analogous to P1 in the human. Both are positive middle-latency auditory-evoked potentials, present at slow click rates during wakefulness and REM sleep but absent during slow-wave sleep. Wave A has been recorded in the parabrachial and medial tegmental areas of the midbrain and in thalamic target projections of the reticular activating system. Two nuclei in this system, the pedunculopontine tegmental (PPT) and laterodorsal tegmental (LDT) nuclei, contain cholinergic cells; the cholinergic antagonist scopolamine eliminates Wave A. To test whether PPT and LDT were important in Wave A generation, we attempted to lesion these nuclei bilaterally in 11 cats. Wave A was markedly diminished or absent in all but 2 cats, in which the lesions did not include PPT. Loss of choline acetyltransferase-positive cells in PPT, but not LDT, was correlated with effects on Wave A, i.e. greatest cell loss occurred in cats in which Wave A disappeared, and least cell loss in cats with no change in Wave A. We conclude that the PPT nucleus, and particularly its cholinergic cell component, is essential for Wave A generation and suggests that a similar substrate may be significant for generation of the human P1.
Animals↗
Cholinergic neurons of the feline pontomesencephalon. II. Ascending anatomical projections.
Immunoreactivity for choline acetyltransferase (ChAT) was analyzed in unoperated cats and in cats in which stereotaxic lesions were made in the pedunculopontine and laterodorsal tegmental nuclei. The fine reaction product revealed moderate to dense ChAT-immunoreactive fiber plexuses throughout the telencephalon, diencephalon, and midbrain. A pontomesencephalic origin of cholinergic innervation to virtually every nucleus of the diencephalon, as well as to various midbrain and basal telencephalic sites was indicated in the cats with lesions, in which the optical density of ChAT-immunoreactivity was significantly decreased as compared to controls. Pontomesencephalic lesions produced no changes, however, in the density of ChAT staining in the cerebral cortex, basolateral amygdala, or caudate nucleus. In addition to ChAT-positive terminal fiber arborizations which were widely distributed, cholinergic fibers-of-passage were traced in the unoperated and operated feline brains. The general course of ChAT fibers cut in cross-section was followed in successive transverse levels, and although pathways originating from the pedunculopontine nucleus demonstrated orientations in every direction, many demonstrated a rostral course. A particularly dense aggregate of ascending ChAT-positive fibers was localized in the dorsolateral sector of the pedunculopontine area which could be followed at more rostral levels into the central tegmental fields and the compact part of the substantia nigra. From the central tegmental fields, numerous ChAT-immunopositive fibers cut in cross-section continued to course rostrally in the intralaminar, reticular and lateroposterior nuclei of the thalamus, and a distinct bundle of ChAT fibers coursing dorsolaterally was observed medial to the optic tract ascending to the lateral geniculate. ChAT fibers with dorsolateral orientations were additionally observed in the zona incerta, ventral anterior thalamus, and ansa lenticularis on route to the reticular thalamus, the globus pallidus, and the substantia innominata. Pathways consisting of fibers traced from ChAT-containing cells in the laterodorsal tegmental nucleus could be traced to medial structures such as the periaqueductal gray, ventral tegmental area and dorsal raphe. Medially placed ChAT fibers were additionally followed through the ventral tegmental area, the midline thalamus, and the hypothalamus, up to the medial and lateral septal nuclei. The trajectories of the ascending cholinergic pathways from the pontomesencephalon are discussed in relation to locally generated electrophysiological responses in the cat.
Afferent Pathways↗
The pontomesencephalotegmental cholinergic system does not degenerate in Alzheimer's disease.
The pedunculopontine and laterodorsal tegmental nuclei comprising the pontomesencephalotegmental (PMT) cholinergic system were examined for the presence of neuropathology and loss of presumed cholinergic cells in patients diagnosed with Alzheimer's disease-senile dementia of the Alzheimer type (AD-SDAT), Parkinsonian dementia, and multi-infarct dementia. Although neurofibrillary changes and plaque-like entities were observed in both nuclei in AD-SDAT and Parkinson's disease dementia, these pathologic indices were not seen consistently in control individuals or in those with multi-infarct dementia, and in none of the diagnostic categories was loss of neuronal somata found in the PMT cholinergic complex. Because appreciable degeneration of cholinergic neurons does occur in the basal forebrain in AD-SDAT, it is concluded that cholinergic phenotype alone is not a sufficient condition indicating predilection for neuronal loss in that dementing illness.
Aged↗
Cholinergic projections to the substantia nigra from the pedunculopontine and laterodorsal tegmental nuclei.
The cholinergic innervation of the compact and reticular parts of the substantia nigra in the rat was investigated by use of highly sensitive retrograde and anterograde tract-tracing methods in combination with choline acetyltransferase immunohistochemistry. The fluorescent tracers True Blue, propidium iodide, or fluorogold were infused preferentially into either nigral subnucleus. Cells positive for choline acetyltransferase and retrograde tracer were found in both the pedunculopontine and laterodorsal tegmental nuclei, although considerably more double-labeled somata were observed in the former than in the latter component of the pontomesencephalotegmental cholinergic complex. Approximately 2-3 times more cholinergic cells were labeled in the peduculopontine and laterodorsal tegmental nuclei when tracer injections were centered in the compact nigral subdivision than when infusions of about the same size were confined totally to the reticular part. Infusions of the anterogradely transported tracer Phaseolus vulgaris leucoagglutinin into the pontomesencephalotegmental cholinergic complex resulted in uptake and transport of that label to both nigral subnuclei, and some of the Phaseolus vulgaris leucoagglutinin-accumulating somata and proximal processes also demonstrated choline acetyltransferase-like immunoreactivity. The Phaseolus vulgaris agglutinin-labeled entities in the substantia nigra exhibited terminal-like profiles that were reminiscent of the pattern of nigral choline acetyltransferase-positive puncta demonstrated immunohistochemically by use of nickel ammonium sulfate enhancement of the final reaction product in the avidin-biotin procedure. These observations strongly support the contention that the pontomesencephalotegmental cholinergic complex is the major source of cholinergic projections to both the compact and reticular portions of the rat substantia nigra.
Animals↗
Nerve growth factor receptor is associated with cholinergic neurons of the basal forebrain but not the pontomesencephalon.
Sequential immunohistochemical demonstration of nerve growth factor receptor and cholinergic acetyltransferase on the same tissue section in the rat revealed that approximately 92% of all cholinergic neurons in the basal forebrain possessed that receptor. Only 0.9% of the neurons demonstrating nerve growth factor receptor in the basal nuclear complex lacked the cholinergic synthetic enzyme, and a similarly small percentage of cholinergic cells, 7.1%, were choline acetyltransferase-positive but nerve growth factor receptor-negative. Affiliation of nerve growth factor receptor with structural entities morphologically indistinguishable from those demonstrating choline acetyltransferase on separate but corresponding tissue sections was also observed in the telencephalic fiber tracts and terminal fields of basal forebrain cholinergic neurons, including cholinergic puncta in the reticular nucleus of the thalamus. Nerve growth factor receptor was not found in association with choline acetyltransferase-positive somata of the pedunculopontine and laterodorsal tegmental nuclei, however, nor were fibers immunoreactive for nerve growth factor receptor observed originating from those cell bodies. These results suggest that nerve growth factor receptor, which is probably synthesized in cholinergic basal forebrain somata and transported throughout their dendritic and axonal arbors, has a physiologic role in those cells in the adult nervous system. This does not appear to be the case for phenotypically similar neurons of the pontomesencephalotegmental cholinergic complex.
Animals↗
Cholinergic systems in the rat brain: IV. Descending projections of the pontomesencephalic tegmentum.
Descending projections from cholinergic neurons in the pedunculopontine and laterodorsal tegmental nuclei, collectively referred to as the pontomesencephalotegmental (PMT) cholinergic complex, were studied by use of the fluorescent retrograde tracers fluorogold, true blue, or Evans Blue in combination with choline acetyltransferase (ChAT) immunohistochemistry of acetylcholinesterase (AChE) pharmacohistochemistry. Pedunculopontine somata positive for ChAT or staining intensely for AChE were retrogradely labeled with fluorescent tracers following infusions into the motor nuclei of cranial nerves 5, 7, and 12. ChAT-positive cells in both the pedunculopontine and laterodorsal tegmental nuclei demonstrated projections to the vestibular nuclei, the spinal nucleus of the 5th cranial nerve, deep cerebellar nuclei, pontine nuclei, locus ceruleus, raphe magnus nucleus, dorsal raphe nucleus, median raphe nucleus, the medullary reticular nuclei, and the oral and caudal pontine reticular nuclei. Fluorescent tracers used in combination with AChE pharmacohistochemistry corroborated these projections and, in addition, provided evidence for cholinergic pontomesencephalic projections to the lateral reticular nucleus and inferior olive. The majority of retrogradely labeled neurons demonstrating ChAT-like immunoreactivity were found ipsilateral to the injection site, but, in all cases, tracer-containing cholinergic cells contralateral to the infused side of the brain were detected also. More retrogradely labeled cells containing ChAT were observed in the pedunculopontine tegmental than in the laterodorsal tegmental nucleus following tracer injections at all sites with the exceptions of the locus ceruleus and dorsal raphe nucleus where the converse profile was observed. None of the pedunculopontine or laterodorsal tegmental cells immunopositive for ChAT or stained intensely for AChE contained retrogradely transported tracers following dye infusions into the cerebellar cortex or cervical spinal cord. Triple-label experiments using two tracers infused into different sites in the same animal revealed that individual ChAT-immunoreactive cells in the PMT cholinergic complex projected to more than one hindbrain site in some cases and had ascending projections as well. Certain ChAT-positive somata in the pedunculopontine and laterodorsal tegmental nuclei were found in close association with several fiber tracts, including the superior cerebellar peduncle, lateral lemniscus, dorsal tegmental tract, and medial longitudinal fasciculus.
Acetylcholinesterase↗
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 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 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↗
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↗
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↗
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↗
Cholinergic projections from the basal forebrain to frontal, parietal, temporal, occipital, and cingulate cortices: a combined fluorescent tracer and acetylcholinesterase analysis.
The morphologies, intercellular organization, and cortical projection patterns of putative cholinergic neurons in the basal forebrain of the rat were examined by use of fluorescent tracer histology in combination with the pharmacohistochemical regimen for acetylcholinesterase (AChE). Intensity staining AChE-containing cells projecting to frontal sensorimotor (Area 10), parietal (Area 2), and temporal (Area 4) cortices were found ipsilaterally in nucleus preopticus magnocellularis, in nucleus basalis, and in association with the substantia innominata, the ansa lenticularis, and the lateral hypothalamic area; an essentially rostrocaudal topography was observed for these projections. AChE-containing pathways to cingulate (Area 29) and visual (Area 17) cortices derived from ipsilateral somata associated with the vertical and horizontal limbs of the diagonal band, nucleus preopticus magnocellularis, rostral portions of nucleus basalis, and the substantia innominata. Neurons innervating Area 29 were generally located more rostrally than those giving rise to AChE afferents to Area 17. The vast majority of cells appeared to innervate relatively discrete areas of the cortex. Evidence for collateralization was found only in neurons projecting to visual and cingulate cortices, and these represented only 3.2% of the cells providing AChE afferents to Areas 17 and 29. The basal forebrain AChE projection cells were typically large (greater than 25 micron in maximum cell body extent), and their somata were predominantly oval, with lesser proportions being fusiform or triangular. Many were organized in clusters, particularly in nucleus basalis.
Acetylcholine↗
Cholinergic projections to the basolateral amygdala: a combined Evans Blue and acetylcholinesterase analysis.
The origins and acetylcholinesterase (AChE, EC 3.1.1.7) content of neurons projecting to the AChE-rich basolateral amygdala were studied by infusing Evans Blue (EB), a retrogradely transported fluorescent label, into that neural region and, following microscopic evaluation of labelled somata, staining the same tissue sections for AChE according to the pharmacohistochemical regimen. The following basal forebrain areas contained cells labelled with EB: the lateral preoptic area, ventral pallidum, nuclei of the diagonal band, medial septal nucleus, bed nucleus of the stria terminalis, and substantia innominata. The majority of the basal forebrain neurons projecting to the basolateral amygdala stained intensely for AChE, suggesting that they were cholinergic. In the brainstem, EB-labelled neurons staining intensely for AChE were found less frequently, but a few were observed in the nucleus tegmenti pendunculopontis, locus ceruleus, subcerulear region, and reticular formation. Cells accumulating EB after basolateral amygdala infusion but demonstrating no, weak, or moderate AChE activity were seen in the orbitofrontal, anterior cingulate, temporal, and insular cortices; the mediodorsal, paraventricular, and parataenial nuclei of the thalamus; the periventricular gray substance; the ventromedial mesencephalic tegmentum; the lateral and compact portions of the substantia nigra; the dorsal raphe; the dorsal tegmental nucleus; and the dorsal parabrachial nucleus. On the basis of staining intensity, intracellular organization of the AChE reaction product, and previous results in the literature, we conclude that the major cholinergic input to the basolateral amygdala derives from the basal forebrain.
Acetylcholinesterase↗