Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.7 (acetylcholinesterase)
 28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Four groups of monkeys (Callithrix jacchus) were injected with saline or increasing amounts of the immunotoxin, ME20.4 IgG-saporin, directly into the basal nucleus of Meynert via a frontal trajectory which avoided damage to the overlying basal ganglia. ME20.4 IgG binds to the primate p75 low-affinity neurotrophin receptor, when the saporin derivitized antibody is injected into the basal forebrain, it selectively destroys the magnocellular neurons of the basal nucleus of Meynert which are the cells of origin of the cholinergic projection to the neocortex. The highest dose of ME20.4 IgG-saporin produced a significant impairment on acquisition of a perceptually difficult visual discrimination. There was no significant effect on retention of tasks learnt before or after surgery, nor on concurrent acquisition of several perceptually easy discriminations or serial reversal of an easy discrimination. These results suggest that the impairment is not due to visual, motor or motivational difficulties and does not consist of difficulties with the formation of reward associations. Rather the impairment is largely confined to acquisition of perceptual discriminations. There was a significant correlation between the density of ME20.4 immunostaining in the basal nucleus of Meynert and the density of acetylcholinesterase histochemical staining in the frontal and temporal cortex and an inverse correlation between both of these and the degree of learning impairment in the animals. Lesioned animals also showed significant impairment on acquisition and reversal of perceptually easy discriminations when treated with a dose of scopolamine which did not impair performance in control animals. These results provide further evidence that cortical cholinergic neurotransmission contributes to certain forms of learning. The availability of a selective cholinergic immunotoxin effective in primates provides an important new tool for the study of cholinergic function and its involvement in ageing, Alzheimer's disease and other pathological states.
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PMID:Learning impairments following injection of a selective cholinergic immunotoxin, ME20.4 IgG-saporin, into the basal nucleus of Meynert in monkeys. 930 Apr 25

The basal forebrain cholinergic system is involved in different forms of memory. To study its role in social memory in sheep, an immunotoxin, ME20.4 immunoglobulin G (IgG)-saporin, was developed that is specific to basal forebrain cholinergic neurons bearing the p75 neurotrophin receptor. The distribution of sheep cholinergic neurons was mapped with an antibody against choline acetyltransferase. To assess the localization of the p75 receptor on basal forebrain cholinergic neurons, the distribution of p75 receptor-immunoreactive neurons with ME20.4 IgG was examined, and a double-labeling study with antibodies against choline acetyltransferase and p75 receptor was undertaken. The loss of basal forebrain cholinergic neurons and acetylcholinesterase fibers in basal forebrain projection areas was assessed in ewes that had received intracerebroventricular injections of the immunotoxin (50, 100 or 150 microg) alone, as well as, in some of the ewes treated with the highest dose, with bilateral immunotoxin injections in the nucleus basalis (11 microg/side). Results indicated that choline acetyltransferase- and p75 receptor-immunoreactive cells had similar distributions in the medial septum, the vertical and horizontal limbs of the band of Broca, and the nucleus basalis. The double-labeling procedure revealed that 100% of the cholinergic neurons are also p75 receptor positive in the medial septum and in the vertical and horizontal limbs of the band of Broca, and 82% in the nucleus basalis. Moreover, 100% of the p75 receptor-immunoreactive cells of these four nuclei were cholinergic. Combined immunotoxin injections into ventricles and the nucleus basalis produced a near complete loss (80-95%) of basal forebrain cholinergic neurons and acetylcholinesterase-positive fibers in the hippocampus, olfactory bulb and entorhinal cortex. This study provides the first anatomical data concerning the basal forebrain cholinergic system in ungulates. The availability of a selective cholinergic immunotoxin effective in sheep provides a new tool to probe the involvement of basal forebrain cholinergic neurons in cognitive processes in this species.
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PMID:Distribution and co-localization of choline acetyltransferase and p75 neurotrophin receptors in the sheep basal forebrain: implications for the use of a specific cholinergic immunotoxin. 1137 45

The involvement of the basal forebrain cholinergic system has been extensively investigated in instrumental learning but little is known of its participation in social memory, especially in the memorization of individual traits of a conspecific. The present study tested in sheep its contribution to both instrumental learning and individual offspring recognition. Six weeks before parturition, ewes received injections of a specific cholinergic immunotoxin (ME20.4 IgG-saporin) into the lateral ventricles (150 microg) and in some cases additional immunotoxin injections into the nucleus basalis (11 microg/side). After 3 weeks of recovery, ewes were trained on a classical instrumental visual discrimination task known to be sensitive to cholinergic deficits. The formation of memory of offspring was assessed through both olfactory and visual/auditory recognition tasks. Olfactory recognition was tested by presenting at suckling successively an alien and the familiar lamb at 2 and 4 h after parturition. Visual/auditory recognition of the lamb was performed using a non-olfactory discrimination test between the familiar and an alien lamb after 12 h of mother-young contact. The lesion extent was assessed by counting choline acetyltransferase-immunopositive neurons in the basal forebrain and measuring the density of acetylcholinesterase fibers in different target areas. Results showed that immunotoxic lesions delayed acquisition of the instrumental visual discrimination. Moreover, olfactory recognition of the lamb was severely impaired while visual/auditory lamb recognition was marginally altered. There was no evidence for sensorimotor or motivational deficits. Importantly, impairment was observed in animals for which loss of basal forebrain cholinergic neurons and their efferent fibers was higher than 75%, while striatal cholinergic neurons and Purkinje cells were unaffected. This study provides evidence that the basal forebrain cholinergic system contributes not only to instrumental but also to social learning. In addition, the cholinergic modulation seems of importance for processing visual and olfactory modalities. However, since only extensive lesions affect performance, this indicates that the basal forebrain cholinergic system possesses substantial reserve capacity to sustain cognitive functions.
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PMID:Extensive immunolesions of basal forebrain cholinergic system impair offspring recognition in sheep. 1156 21

The nucleus basalis (NB) in the basal forebrain provides most of the cholinergic input to the neocortex and has been implicated in a variety of cognitive functions related to the processing of sensory stimuli. However, the role that cortical acetylcholine release plays in perception remains unclear. Here we show that selective loss of cholinergic NB neurons that project to the cortex reduces the accuracy with which ferrets localize brief sounds and prevents them from adaptively reweighting auditory localization cues in response to chronic occlusion of one ear. Cholinergic input to the cortex was disrupted by making bilateral injections of the immunotoxin ME20.4-SAP into the NB. This produced a substantial loss of both p75 neurotrophin receptor (p75(NTR))-positive and choline acetyltransferase-positive cells in this region and of acetylcholinesterase-positive fibers throughout the auditory cortex. These animals were significantly impaired in their ability to localize short broadband sounds (40-500 ms in duration) in the horizontal plane, with larger cholinergic cell lesions producing greater performance impairments. Although they localized longer sounds with normal accuracy, their response times were significantly longer than controls. Ferrets with cholinergic forebrain lesions were also less able to relearn to localize sound after plugging one ear. In contrast to controls, they exhibited little recovery of localization performance after behavioral training. Together, these results show that cortical cholinergic inputs contribute to the perception of sound source location under normal hearing conditions and play a critical role in allowing the auditory system to adapt to changes in the spatial cues available.
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PMID:Cortical cholinergic input is required for normal auditory perception and experience-dependent plasticity in adult ferrets. 2357 62

Cholinergic inputs to the auditory cortex can modulate sensory processing and regulate stimulus-specific plasticity according to the behavioural state of the subject. In order to understand how acetylcholine achieves this, it is essential to elucidate the circuitry by which cholinergic inputs influence the cortex. In this study, we described the distribution of cholinergic neurons in the basal forebrain and their inputs to the auditory cortex of the ferret, a species used increasingly in studies of auditory learning and plasticity. Cholinergic neurons in the basal forebrain, visualized by choline acetyltransferase and p75 neurotrophin receptor immunocytochemistry, were distributed through the medial septum, diagonal band of Broca, and nucleus basalis magnocellularis. Epipial tracer deposits and injections of the immunotoxin ME20.4-SAP (monoclonal antibody specific for the p75 neurotrophin receptor conjugated to saporin) in the auditory cortex showed that cholinergic inputs originate almost exclusively in the ipsilateral nucleus basalis. Moreover, tracer injections in the nucleus basalis revealed a pattern of labelled fibres and terminal fields that resembled acetylcholinesterase fibre staining in the auditory cortex, with the heaviest labelling in layers II/III and in the infragranular layers. Labelled fibres with small en-passant varicosities and simple terminal swellings were observed throughout all auditory cortical regions. The widespread distribution of cholinergic inputs from the nucleus basalis to both primary and higher level areas of the auditory cortex suggests that acetylcholine is likely to be involved in modulating many aspects of auditory processing.
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PMID:The cholinergic basal forebrain in the ferret and its inputs to the auditory cortex. 2494 75