Cholinergic pathways and the ascending reticular activating system of the human brain.
Explore the source record for details and available documents.
Acetylcholine↗
Biomedical subjects
M M Mesulam
Publications and source records attributed to M M Mesulam.
Selectively distributed processing of visual object recognition in the temporal and frontal lobes of the human brain.
Evoked potentials to visually driven cognitive tasks were recorded through depth electrodes placed bilaterally within the amygdala, hippocampus, midtemporal and inferotemporal cortex, and lateral frontal cortex of 6 epileptic patients. Task-related differential response patterns were used to identify the recording sites engaged by specific aspects of visual encoding. In this group of 6 patients, the amygdala was most frequently engaged in encoding the familiarity of faces; midtemporal and inferotemporal cortex, in encoding perceptual identity and object categorization; and lateral frontal cortex, in holding visual object information in working memory. The two aspects of encoding that most frequently engaged the hippocampal region were related to working memory and object categorization. The processing of complex visual knowledge is thus anatomically distributed but regionally specialized. These experiments also showed that identical input and output parameters can engage different areas of the brain depending on the nature of the instructional set.
Adult↗
Postnatal development of cortical acetylcholinesterase-rich neurons in the rat brain: permanent and transient patterns.
The development of acetylcholinesterase (AChE) activity within cortical neurons of the rat brain was investigated using a histochemical method. The fate of these neurons in later stages of development was studied in animals in which AChE within cortical axons (mostly cholinergic) had been depleted by lesions of the cholinergic neurons of the basal forebrain or by injections of diisopropyl fluorophosphate. We designated neurons with medium to high intensity of reaction product as AChEH and neurons with a low intensity of reaction product as AChEL. Four groups of AChEH cortical neurons were detected: (1) AChEH Cajal-Retzius cells were present in layer I at birth (P0) and decreased steadily in number until none could be detected at P17 or thereafter. (2) AChEH neurons within layer VI and underlying white matter were present at P0, peaked in number and staining intensity at P8-P9, showed a moderate decrease in number at P11-P13 and a further decrease into adulthood. (3) AChEH polymorphic intracortical neurons appeared at P3-P4 in deep cortical layers and by P9 were present in layers II-VI. They continued to increase in number through P11-P14 at which time they displayed the adult pattern and were found in all cortical areas. (4) A large population of AChEH pyramidal neurons appeared at P1-P4, peaked at P8-P10 and was no longer visible at P21. In the adult cerebral cortex, few pyramidal neurons displayed AChE activity and these were almost always of the AChEL type. These results indicate that the AChE within cortical neurons is developmentally regulated and that the content of this enzyme helps to differentiate cortical neurons into distinct populations. The transient expression of AChE activity within cortical neurons suggests a role for this enzyme in the development of the cerebral cortex.
Acetylcholinesterase↗
Human striatum: the distribution of neurofibrillary tangles in Alzheimer's disease.
The distribution of neurofibrillary tangles and senile plaques was surveyed in the striatum of Alzheimer's disease cases. Neurofibrillary tangles were present throughout the striatum, but displayed significantly higher densities in the nucleus accumbens, olfactory tubercle and tail of the caudate nucleus. Senile plaques with dense amyloid cores showed a similar pattern of distribution. By contrast, non-cored senile plaques were homogeneously distributed in all striatal territories. No tangles and few plaques were observed in the striatum of control cases. These findings suggest that the 'limbic' striatum is preferentially vulnerable to pathology in Alzheimer's disease.
Adult↗
Cholinesterase activity in the plaques, tangles and angiopathy of Alzheimer's disease does not emanate from amyloid.
Previous histochemical observations in our laboratory have demonstrated the presence of butyrylcholinesterase and an enzymatically altered form of acetylcholinesterase activity in the plaques, tangles and amyloid-containing vessels of Alzheimer's disease. These findings suggested possible interactions between amyloid and cholinesterases. In this study we employed a cholinesterase biochemical assay to determine whether the amyloid precursor protein either had cholinesterase activity itself or influenced the enzymatic activity of cholinesterases. None of the three amyloid precursor sequences used (695, 751, 770, up to 16 micrograms/ml) exhibited any acetylcholinesterase or butyrylcholinesterase activity that could be detected by our method. In addition, none of the amyloid precursor proteins influenced the enzymatic activity of purified acetylcholinesterase or butyrylcholinesterase in a specific manner. It is therefore quite unlikely that amyloid can, by itself, account for the intense cholinesterase activity associated with the pathological lesions of AD.
Alzheimer Disease↗
The impact of aging on curiosity as measured by exploratory eye movements.
OBJECTIVE: To investigate changes in novelty-seeking behavior (curiosity) associated with normal aging. BACKGROUND: Recently, we demonstrated that patients with a diagnosis of probable Alzheimer's disease display diminished novelty-seeking behavior as measured by exploratory eye movements. Nondemented, elderly individuals are often depicted in clinical descriptions as exhibiting diminished curiosity and increased disengagement from their surroundings. However, this behavior has not been systematically investigated as a function of normal aging. SETTING: University hospital center studying aging and dementia. SUBJECTS: Fourteen active, healthy elderly subjects (mean age, 72 years) and 16 middle-aged subjects (mean age, 42 years) matched for education and estimated IQ. MEASURES: Exploratory eye movements were recorded in response to visual stimuli that varied in novelty, complexity, and incongruity. RESULTS: Both older and middle-aged subjects (1) spent significantly more time exploring the more irregular or incongruous of two simultaneously presented stimuli, (2) spent increasingly less time looking at a repeating visual stimulus paired with a stimulus that changed with each trial, and (3) exhibited the same degree of overall exploration of a visual scene and devoted an approximately equal amount of attention to an unexpected element within it. As a group, older subjects spent slightly less time than middle-aged subjects examining incongruous stimuli. However, 71% (10/14) of older subjects performed within 1 SD of the mean of middle-aged subjects and 21% (3/14) performed as well as the top 50% (8/16) of middle-aged controls. CONCLUSIONS: The drive for curiosity, as measured by exploratory eye movements, can be well preserved in older individuals. Further research is needed to determine if the integrity of this drive can serve as a marker of "successful aging" and to identify which physiological and psychological factors influence its preservation through the life cycle.
Adult↗
Impairment of spatially directed attention in patients with probable Alzheimer's disease as measured by eye movements.
OBJECTIVE: To investigate changes in spatially directed attention in patients with a diagnosis of probable Alzheimer's disease (AD). BACKGROUND: Impaired attention in patients with probable AD has not been the subject of extensive research. Yet recent reports suggest that attentional deficits may be an important early feature of the disease in a subset of patients. SETTING: University hospital center studying dementia and aging. SUBJECTS: Ten mild to moderately impaired patients diagnosed as having probable AD, by National Institute of Neurologic and Communicative Diseases and Stroke criteria, and 11 healthy age- and education-matched controls. MEASURES: Eye movements were recorded as subjects participated in two experiments designed to measure spatially directed attention. Subjects were instructed to (1) attend to and fixate a target appearing randomly to the right or left of a central marker and (2) direct attention to and fixate a target appearing randomly in one of four peripheral locations. RESULTS: Patients with probable AD exhibited fewer accurate trials and longer saccade latencies in both tasks. As a group, patients performed worse in the second task that placed increased demands on attention. However, the performance of patients in this second experiment varied. Four patients performed significantly worse than all other patients, while three patients performed as well as controls. Errors in the second task were reviewed to identify specific types of attentional deficits. Six empirically derived error patterns were classified into one of two major categories: perseveration and impersistence. Seven of 10 patients made greater than 50% errors of perseveration, and three of 10 made greater than 50% errors of impersistence. CONCLUSIONS: Impairment of attention may be an early feature of AD and a prominent clinical characteristic of some patients. The differences observed in error types made by patients may reflect the varied distribution of neuropathologic changes affecting structures that mediate aspects of attention. The architecture of eye movements can be used as a physiologic measure that should provide useful information for the diagnosis and clinicopathologic subtyping of patients with AD.
Aged↗
Butyrylcholinesterase reactivity differentiates the amyloid plaques of aging from those of dementia.
In a sample of consecutively received, 4 demented and 4 age-matched nondemented brains, the total cortical area covered by plaque-like A beta amyloid and butyrylcholinesterase deposits was measured at two regions of the temporal cortex with the help of computed densitometry. Demented as well as age-matched nondemented brains contained A beta and butyrylcholinesterase-positive plaques. The total cortical area covered by the A beta precipitates was higher in demented individuals but there was overlap with the values seen in the specimens from nondemented individuals. The proportional plaque area displaying butyrylcholinesterase reactivity was very significantly and five fold to sixfold higher in the demented than in the nondemented group and there was no overlap between the two populations. Diffuse A beta deposits in nondemented elderly brains may represent a benign or preclinical stage of plaque deposition with relatively little pathological effect on brain tissue and mental function. Our results suggest that the progressively more extensive butyrylcholinesterase reactivity of plaques may participate in their transformation from a relatively benign form to pathogenic structures associated with neuritic degeneration and dementia.
Aged↗
Two types of cholinergic projections to the rat amygdala.
The cholinergic innervation of the rat amygdala was studied immunohistochemically with antibodies against choline acetyltransferase and the low affinity p75 nerve growth factor receptor in normal rats and in rats lesioned with an immunotoxin, 192 IgG-saporin, directed against the p75 nerve growth factor receptor. The density of choline acetyltransferase-positive fibers was high in the nucleus of the lateral olfactory tract, the basolateral nucleus, and the amygdalohippocampal area; medium in the lateral nucleus, the cortical nucleus, the accessory basal nucleus, the periamygdaloid cortex, and the anterior amygdaloid area; and low in the medial and central nuclei. Nerve growth factor receptor-positive fibers were of medium density in the lateral nucleus, the accessory basal nucleus, the cortical nucleus, the anterior amygdaloid area, the periamygdaloid cortex, and the amygdalohippocampal area. The medial nucleus and the central nucleus displayed a low density of nerve growth factor receptor-positive fibers. The basolateral nucleus and the nucleus of the lateral olfactory tract also contained a low density of nerve growth factor receptor-positive fibers even though the two nuclei displayed the highest density of choline acetyltransferase-positive fibers in the amygdala. Injections of 192 IgG-saporin induced a complete loss of cholinergic nerve growth factor receptor-positive neurons in the basal forebrain but spared a subpopulation of nerve growth factor receptor-negative cholinergic neurons in the nucleus basalis-substantia innominata complex. Following 192 IgG-saporin injections, choline acetyltransferase-positive and acetylcholinesterase-positive fibers were essentially unchanged in the nucleus of the lateral olfactory tract and the basolateral nucleus and showed a partial reduction in the remaining nuclei of the amygdaloid complex. Cholinergic fibers emanating from cholinergic cell group 4 neurons reached the amygdala via the stria terminalis and the ventral amygdalofugal pathway. These observations indicate that two amygdaloid nuclei, the nucleus of the lateral olfactory tract and the basolateral nucleus, receive their cholinergic projections predominantly, if not exclusively, from nerve growth factor receptor-negative cholinergic neurons whereas all remaining amygdaloid regions receive fibers from nerve growth factor receptor-negative as well as nerve growth factor receptor-positive cholinergic neurons.
Amygdala↗
Human striatum: chemoarchitecture of the caudate nucleus, putamen and ventral striatum in health and Alzheimer's disease.
The morphology and distribution of perikarya positive for choline acetyltransferase, somatostatin, calcium binding protein (calbindin D28K) and nicotinamide adenine dinucleotide phosphate diaphorase were surveyed in the human striatum. Choline acetyltransferase and somatostatin antibodies labeled separate populations of large striatal interneurons. Somatostatin immunoreactivity and nicotinamide adenine dinucleotide phosphate diaphorase (nitric oxide synthase) activity were completely co-localized. Calbindin antibody identified two distinct groups of striatal neurons: (1) numerous medium-sized, lightly stained neurons, probably analogous to striatopallidal projection neurons in the rat, and (2) much less numerous, large, darkly stained neurons. Half of the latter group, but none of the former, were also nicotinamide adenine dinucleotide phosphate diaphorase-positive. Somatostatin-positive and medium-sized, calbindin-positive neurons were more numerous in the caudate nucleus than in the putamen or ventral striatum. By contrast, large calbindin-immunoreactive neurons were more frequently encountered in the putamen. Choline acetyltransferase-positive neurons were evenly distributed across striatal components. In aged control subjects, the size of large, darkly stained calbindin-positive neurons was reduced relative to young subjects. Aging had no effect on somatostatin-, medium-sized calbindin-, or choline acetyltransferase-positive neurons. However, in histologically confirmed cases of Alzheimer's disease, there was a selective, 75% loss of choline acetyltransferase-immunoreactive perikarya from the ventral striatum, but not from the dorsal striatum, compared to aged controls. Furthermore, the remaining cholinergic neurons in the ventral striatum of Alzheimer's disease cases were significantly smaller than similar neurons in controls. These results indicate that various striatal components which have been shown to differ in their anatomical connectivity and functional specialization, also differ in their neurochemical signatures. The specific and marked loss of choline acetyltransferase-positive neurons from the ventral striatum in Alzheimer's disease is consistent with the characteristic cholinergic and 'limbic' pathology in this disease.
Adult↗
Qualitative mapping of cerebral blood flow and functional localization with echo-planar MR imaging and signal targeting with alternating radio frequency.
PURPOSE: To create qualitative maps of cerebral blood flow (CBF) with the EPISTAR (echo-planar imaging and signal targeting with alternating radio frequency) technique. MATERIALS AND METHODS: The EPISTAR technique was performed in a pig model of hypercapnia and then tested in 26 volunteers by using various paradigms for cortical activation. Echo-planar images were acquired with and without use of a radio-frequency inversion pulse applied to inflowing arterial spins. A qualitative map of CBF was then created by subtracting the image obtained without the radio-frequency pulse from that obtained with the radio-frequency pulse. RESULTS: Progressively more distal portions of the tagged vessels were seen as the inflow time was lengthened until cortical enhancement was seen for inflow times of approximately 1 second or longer. Signal intensity increases from rest to sensorimotor activation ranged from 13% to 193%. CBF changes in the motor strip, primary visual cortex, and the motor area for eye movements were well localized to the cortical gray matter ribbon. CONCLUSION: The EPISTAR technique is a rapid, noninvasive means for creating qualitative maps of CBF.
Animals↗
Paraneoplastic temporal lobe epilepsy with testicular neoplasm and atypical amnesia.
We report a patient who, at age 38, presented with temporal lobe seizures and an atypical memory disorder 3 years before the discovery of a testicular tumor. Detailed neuropsychological testing revealed a relatively isolated amnestic syndrome. The amnesia was atypical as the patient could retain information for hour-long periods, only to lose it later. Serologic studies revealed the presence of a circulating autoantibody that demonstrated an unusual affinity for the nucleolus of cerebral cortical neurons. Western blot analysis of cortical neurons revealed that this antibody reacted with proteins different from other previously identified paraneoplastic neurologic antigens (Hu, Yo, Ri). We believe this to be a case of paraneoplastic limbic encephalitis secondary to the testicular tumor. This patient presents unique characteristics with respect to the mode of presentation, features of the amnesia, and the presence of a circulating antibody with an unusual reactivity pattern.
Amnesia↗
Differential effects on spatial navigation of immunotoxin-induced cholinergic lesions of the medial septal area and nucleus basalis magnocellularis.
The effects on anatomy and behavior of a ribosomal inactivating protein (saporin) coupled to a monoclonal antibody against the low-affinity NGF receptor (NGFr) were examined. In adult rats, NGFr is expressed predominantly in cholinergic neurons of the medial septal area (MSA), diagonal band nuclei, and nucleus basalis magnocellularis (nBM), but also in noncholinergic cerebellar Purkinje cells. Rats with immunotoxin injections to the MSA, nBM, and lateral ventricle were compared to controls on a spatial and cued reference memory task in the Morris maze. Toxin injections to the MSA slightly impaired the initial, but not asymptotic, phase of spatial navigation. Injections to the nBM impaired all phases of spatial navigation. Cued navigation, however, was not affected in either the MSA or nBM group. The ventricular injections severely affected spatial and cued navigation. Acetylcholinesterase (AChE) histochemistry and NGFr and choline acetyltransferase immunohistochemistry revealed a loss of (1) almost all NGFr-positive cholinergic neurons in the MSA and AChE fibers in hippocampus (MSA group); (2) almost all NGFr neurons in the nBM, some in the MSA, most AChE fibers in neocortex and some in the hippocampus (nBM group), and (3) almost all NGFr neurons in the MSA and nBM and their corresponding hippocampal and cortical AChE fibers (ventricular group). Cholinergic nBM projections to the amygdala were largely preserved in all groups. The amount of cholinergic fiber loss in the cortex correlated modestly, but significantly, with the severity of impairment of the asymptotic phase of performance of the spatial task. An unambiguous interpretation of the anatomical locus of behavioral deficits was not possible because of damage to cholinergic striatal interneurons (nBM group) and to noncholinergic cerebellar Purkinje cells (ventricular group). These data suggest that the cholinergic cortical system is critical to the performance of this spatial memory task. Cholinergic denervation of the hippocampus alone, however, is not sufficient to impair markedly performance of this task.
Animals↗
Complete and selective cholinergic denervation of rat neocortex and hippocampus but not amygdala by an immunotoxin against the p75 NGF receptor.
The immunotoxin 192 IgG-saporin, produced by coupling the ribosome-inactivating protein saporin to the monoclonal 192 IgG antibody against the low-affinity p75 NGF receptor (NGFr), was injected into the cerebral ventricle, septal area, and substantia innominata of adult rats. Injections into the cerebral ventricle induced a complete loss of NGFr-positive basal forebrain neurons and their axons. Extensive loss of cholinergic neurons was found in the septum, diagonal band, and magnocellular preoptic nucleus but not in the nucleus basalis-substantia innominata complex, where many cholinergic, presumably NGFr-negative, neurons remained intact. Cholinergic fibers were completely lost in the neocortex and hippocampus, showed some preservation in allocortical areas, and showed only minor loss in the amygdala. The NGFr-positive cholinergic basal forebrain neurons progressively degenerated during the first 5 d and did not recover after 180 d. The effect of intraventricular 192 IgG-saporin injections on NGFr-positive basal forebrain neurons could be blocked by simultaneous intraventricular injection of colchicine. Intraparenchymal injections into the septal area or substantia innominata damaged cholinergic neurons mainly around the injection sites and reduced their respective cortical and hippocampal projections. Noncholinergic septal neurons containing parvalbumin and noncholinergic neurons containing calbindin-D28k or NADPHd, which were adjacent to cholinergic nucleus basalis-substantia innominata neurons, were not affected by 192 IgG-saporin. The ChAT immunoreactivity in cortical interneurons, habenula, and brainstem was unchanged. Dopaminergic and noradrenergic cortical afferents remained intact. 192 IgG-saporin damaged two neuronal groups outside the basal forebrain that express the p75 NGF receptor: NGFr-positive cerebellar Purkinje cells after intraventricular injection and cholinergic striatal interneurons after injections into the substantia innominata. These results indicate that the immunotoxin 192 IgG-saporin induces a complete and selective lesion of NGFr-positive cholinergic basal forebrain neurons projecting to hippocampus and neocortex.
Acetylcholinesterase↗
Cholinergic innervation of the amygdaloid complex in the human brain and its alterations in old age and Alzheimer's disease.
The cholinergic innervation of the human amygdaloid complex was studied immunohistochemically with a choline acetyltransferase (ChAT) antibody in eight brains: five control and three with Alzheimer's disease (AD). All amygdaloid nuclei displayed ChAT-immunopositive axons and varicosities. The density of these axons reached levels that were higher than in any other part of the forebrain except for the striatum. The highest level of ChAT-immunopositive profiles was seen in the basolateral nucleus and the second highest in the lateral part of the central nucleus. The basomedial, accessory basal, and cortical nuclei, the amygdalohippocampal and cortico-amygdaloid transition areas, as well as the anterior amygdaloid area, showed a moderate density of ChAT-positive varicosities and fibers. The lateral nucleus displayed a relatively low density of cholinergic innervation, and there were only rare ChAT-positive fibers in the medial nucleus. Although the level of cholinergic innervation in the lateral nucleus was relatively lower than in many of the other amygdaloid nuclei, it was approximately equivalent to that of entorhinal cortex, a region that receives one of the heaviest cholinergic inputs in the cerebral cortex. The distribution of the cholinergic fibers as studied by ChAT immunohistochemistry was nearly identical to that observed with AChE histochemistry. Quantitative densitometry in control specimens showed that there was no decline of amygdaloid cholinergic input when middle-aged subjects were compared with senescent subjects. In AD there was a severe and regionally selective depletion of this innervation in the amygdaloid complex. The cortical, accessory basal, and lateral nuclei displayed the most severe loss of ChAT-positive profiles, whereas the basolateral, and especially the central, nuclei displayed relatively little change. There was no consistent relationship between the loss of cholinergic fibers and the density of amyloid plaques and neurofibrillary tangles in amygdaloid nuclei.
Aged↗
Protease inhibitors and indolamines selectively inhibit cholinesterases in the histopathologic structures of Alzheimer's disease.
Neurofibrillary tangles and amyloid plaques express acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity in Alzheimer's disease. We had found that traditional AChE inhibitors such as BW284C51, tacrine and physostigmine were more potent inhibitors of the AChE in normal axons and cell bodies than of the AChE in plaques and tangles. We now report that the reverse pattern is seen with indolamines, carboxypeptidase inhibitor, and the nonspecific protease inhibitor bacitracin. These substances are more potent inhibitors of the cholinesterases in plaques and tangles than of those in normal axons and cell bodies. These results show that the enzymatic properties of plaque and tangle-associated cholinesterases diverge from those of normal axons and cell bodies. The selective susceptibility to bacitracin and carboxypeptidase inhibitor indicates that the catalytic sites of plaque and tangle-bound cholinesterases are more closely associated with peptidase or protease-like properties than the catalytic sites of cholinesterases in normal neurons and axons. This shift in enzymatic affinity may lead to the abnormal protein processing which is thought to play a major role in the pathogenesis of AD. The availability of pharmacological and dietary means for altering brain indolamines raises novel therapeutic possibilities for inhibiting the abnormal cholinesterase activity associated with Alzheimer's disease.
Acetylcholinesterase↗
Differential laminar distribution of acetylcholinesterase and butyrylcholinesterase containing tangles in the cerebral cortex of Alzheimer's disease.
A sensitive histochemical method for the visualization of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity was used to determine the laminar distribution of cholinesterase-positive cortical tangles in Alzheimer's disease (AD). In many cortical areas AChE- and BChE-positive tangles displayed a completely overlapping distribution. In other areas the most superficial layers contained only AChE-positive tangles whereas the deepest layers contained only BChE-positive tangles. These observations suggest that some cholinesterase-positive tangles have a predominantly (if not exclusively) AChE-like reactivity whereas others have a reactivity that is predominantly BChE-like. The intermingling of AChE- and BChE-positive tangles in most cortical areas and layers suggests that there may also be a third population in which the two enzymes are equally prominent in the same tangle.
Acetylcholinesterase↗
Cholinergic innervation of the human thalamus: dual origin and differential nuclear distribution.
The cholinergic innervation of the human thalamus was studied with antibodies against the enzyme choline acetyltransferase (ChAT) and nerve growth factor receptor (NGFr). Acetylcholinesterase histochemistry was used to delineate nuclear boundaries. All thalamic nuclei displayed ChAT-positive axons and varicosities. Only the medial habenula contained ChAT-positive perikarya. Some intralaminar nuclei (central medial, central lateral, and paracentral), the reticular nucleus, midline nuclei (paraventricular and reuniens), some nuclei associated with the limbic system (anterodorsal nucleus and medially situated patches in the mediodorsal nucleus) and the lateral geniculate nucleus displayed the highest density of ChAT-positive axonal varicosities. The remaining sensory relay nuclei and the nuclei interconnected with the motor and association cortex displayed a lower level of innervation. Immunoreactivity for NGFr was observed in cholinergic neurons of the basal forebrain but not in cholinergic neurons of the upper brainstem. The contribution of basal forebrain afferents to the cholinergic innervation of the human thalamus was therefore studied with the aid of NGFr-immunoreactive axonal staining. The anterior intralaminar nuclei, the reticular nucleus, and medially situated patches in the mediodorsal nucleus displayed a substantial number of NGFr-positive varicose axons, presumably originating in the basal forebrain. Rare NGFr-positive axonal profiles were also seen in many of the other thalamic nuclei. These observations suggest that thalamic nuclei affiliated with limbic structures and with the ascending reticular activating system are likely to be under particularly intense cholinergic influence. While the vast majority of thalamic cholinergic input seems to come from the upper brainstem, the intralaminar and reticular nuclei, and especially medially situated patches within the mediodorsal nucleus also appear to receive substantial cholinergic innervation from the basal forebrain.
Acetylcholine↗