Lesions of the cholinergic nuclei in the rat basal forebrain: Excitotoxins vs. an immunotoxin

Waite, Jerene J.; Thal, Leon J.

doi:10.1016/0024-3205(96)00184-1

Cited by 40 publications

(19 citation statements)

References 29 publications

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“…By comparison, excitotoxic lesions of the basal forebrain, which result in lower levels of cortical ChAT depletion (22%-50%; Scremin et al 1991;Waite and Thal 1996;Holschneider et al 1997), demonstrate a greater increase in cortical slow-wave power (15%-81%) and a greater decrease in high-frequency power (20%-58%; Riekkinen et al 1990Riekkinen et al , 1991Holschneider et al 1997). This suggest that some of the electrocortical changes following excitotoxic lesions of the basal forebrain may be due to the added damage of noncholinergic fibers.…”

Section: Discussionmentioning

confidence: 97%

“…Changes in brain electrical power and synchronization following administration of pharmacologic agents or excitotoxic lesions of the basal forebrain may not be reflective entirely of changes in cholinergic tone, in so far as these interventions have been shown to involve noncholinergic neurons also (Wenk et al 1991;Lindefors et al 1992;Muir et al 1993;Waite and Thal 1996). 192 IgG-saporin, an immunotoxin linking an antibody to the low-affinity nerve growth factor receptor p75 to the ribosome inactivating protein saporin, has recently permitted specific lesioning of cholinergic neurons.…”

Section: Introductionmentioning

confidence: 99%

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Changes in electrocortical power and coherence in response to the selective cholinergic immunotoxin 192 IgG-saporin

Holschneider

Waite

Leuchter

et al. 1999

Experimental Brain Research

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Changes in brain electrical activity in response to cholinergic agonists, antagonists, or excitotoxic lesions of the basal forebrain may not be reflective entirely of changes in cholinergic tone, in so far as these interventions also involve noncholinergic neurons. We examined electrocortical activity in rats following bilateral intracerebroventricular administration of 192 IgG-saporin (1.8 μg/ventricle), a selective cholinergic immunotoxin directed to the low-affinity nerve growth factor receptor p75. The immunotoxin resulted in extensive loss of choline acetyl transferase (ChAT) activity in neocortex (80%-84%) and hippocampus (93%), with relative sparing of entorhinalpiriform cortex (42%) and amygdala (28%). Electrocortical activity demonstrated modest increases in 1-to 4-Hz power, decreases in 20-to 44-Hz power, and decreases in 4-to 8-Hz intraand interhemispheric coherence. Rhythmic slow activity (RSA) occurred robustly in toxin-treated animals during voluntary movement and in response to physostigmine, with no significant differences seen in power and peak frequency in comparison with controls. Physostigmine significantly increased intrahemispheric coherence in lesioned and intact animals, with minor increases seen in interhemispheric coherence. Our study suggests that: (1) electrocortical changes in response to selective cholinergic deafferentation are more modest than those previously reported following excitotoxic lesions; (2) changes in cholinergic tone affect primarily brain electrical transmission within, in contrast to between hemispheres; and (3) a substantial

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Changes in electrocortical power and coherence in response to the selective cholinergic immunotoxin 192 IgG-saporin

Holschneider

Waite

Leuchter

et al. 1999

Experimental Brain Research

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“…However, Torres et al (66) found a small but significant impairment on IA retention with saporin NBM lesions. The relative ineffectiveness of immunotoxic NBM lesions to impair memory relative to excitotoxic NBM lesions suggests that the robust memory deficits produced with excitotoxic lesions (67-70) may be caused by damaged amygdalopetal cholinergic projections (35,71,72) and͞or damaged noncholinergic cells (63,(73)(74)(75)(76).…”

Section: Discussionmentioning

confidence: 99%

“…Generally, memory deficits are only consistently produced with icv cholinergic basal forebrain lesions that disrupt Ͼ 75-85% of ChAT activity of the total cholinergic basal forebrain (62)(63)(64). With an experiment using a training protocol similar to that of the current study, Wenk et al (65) found no deficits on several measures of IA, including 48-h retention latency and freezing behavior in rats with saporin lesions of the NBM.…”

Section: Discussionmentioning

confidence: 99%

Lesions of the nucleus basalis magnocellularis induced by 192 IgG-saporin block memory enhancement with posttraining norepinephrine in the basolateral amygdala

Power

Thal

McGaugh

2002

Proc. Natl. Acad. Sci. U.S.A.

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Extensive evidence indicates that drugs and stress hormones act in the basolateral amygdala (BLA) to modulate memory consolidation. The BLA projects to the nucleus basalis magnocellularis (NBM), which sends broad cholinergic projections to the neocortex. NBM-cortex projections have been implicated in learning, memory storage, and plasticity. The current study investigated whether the cholinergic NBM-cortex projections are involved in BLA-mediated modulation of memory consolidation. Bilateral cholinergic cell lesions of the NBM were induced in rats with infusions of 192 IgG-saporin (0.1 g͞0.5 l per side). Additionally, cannulae were implanted bilaterally in the BLA. One week after surgery, the rats were trained in an inhibitory avoidance task and, immediately after training, norepinephrine (0.3 g, 1.0 g, or 3.0 g in 0.2 l) or vehicle (PBS) was infused bilaterally into the BLA. Norepinephrine infusions produced a dose-dependent enhancement of 48-h retention (0.3 g and 1.0 g doses enhanced) in nonlesioned rats but did not affect retention in NBM-lesioned rats. Choline acetyltransferase assays of frontal and occipital cortices confirmed the NBM lesions. These findings indicate that cholinergic NBM-cortex projections are required for BLA-mediated modulation of memory consolidation.acetylcholine ͉ inhibitory avoidance ͉ memory modulation ͉ rat S ystemic administration of drugs, including adrenergic agonists (1-3) and GABAergic antagonists (4-6), given immediately after training, enhances memory for several kinds of training. The basolateral amygdala (BLA) (4, 8-12) and its major efferent pathway, the stria terminalis (13-16), are critically involved in the modulation of memory consolidation induced by posttraining pharmacological treatments. In addition, considerable evidence indicates that memory modulation by systemic drugs requires ␤-adrenergic activation in the BLA (17-21).Inhibitory avoidance (IA) tasks have been used most extensively in memory modulatory studies, as the use of a single training trial enables selective modulation of the consolidation phase of memory. Memory for IA training can be modulated by posttraining intra-BLA infusions of adrenergic (21-25), GABAergic (6,26), opioid peptidergic (19,27,28,87), glucocorticoid (21,30,31), or cholinergic drugs (32-35). As with systemic treatments, memory modulation induced by posttraining intra-BLA drug infusions acting on glucocorticoid, GABA, or opioid receptors requires concurrent ␤-adrenergic activation in the BLA (19,21,36,37). Furthermore, it was shown recently in our laboratory that levels of amygdalar norepinephrine assessed after training predict long-term retention of IA (unpublished findings). The adrenergic-dependent memory modulation further depends upon muscarinic cholinergic activation in the BLA (31-33, 38, 39), which likely originates from the major amygdalopetal projection of the nucleus basalis magnocellularis (NBM) (37).Extensive evidence indicates that the BLA mediates the modulation of memory traces that are processed and͞or stored in othe...

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“…By using the excitotoxin ibotenic acid to damage the basal forebrain, many independent groups were able to mimic the previously observed scopolamine related deficits on a wide variety of tasks. Apart from the behavioural impairment, ibotenic lesions reduced cortical and hippocampal ACh levels by 30-50% (Murrey and Fibiger, 1985;Dunnett et al, 1987;Ridley et al, 1988;Page et al, 1991;Waite and Thai, 1996).…”

Section: Excitotoxic Lesionsmentioning

confidence: 99%

Revisiting the cholinergic hypothesis in the development of Alzheimer's disease

Craig

Hong

McDonald

2011

Neuroscience & Biobehavioral Reviews

402

263

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Alzheimer's disease (AD) is the most common form of dementia affecting the elderly population today; however, there is currently no accurate description of the etiology of this devastating disorder. No single factor theory has been demonstrated as being causative; however, an alternative theory suggests that the interaction of multiple risk factors is responsible for AD. In this thesis I present data suggesting a neuroprotective role for acetylcholine during aging. Using a rat model of cholinergic depletion of the medial septum, I explored the effects of four common risk factors for AD (stress, seizures, stroke and circadian dysfunction) targeted at the hippocampus and examined the effects on measures of hippocampal dependent (water maze) and hippocampal independent (fear conditioning) memory. Here, I propose a role for acetylcholinemediated compensatory mechanisms in the functional recovery observed following sub threshold insults similar to those commonly observed in the elderly. m First and foremost I would like to thank my supervisor, Dr. Robert McDonald. Thank you for your support and encouragement, and for allowing me the independence to pursue my own projects and to learn from my experiences. I would also like to thank Nhung Hong for doing the majority of the cholinergic depletion and stroke surgeries used in this thesis and for teaching me the techniques. I would like to give a huge thank you to Joelle Kopp who was an invaluable asset who assisted in histology and spent many hours on the microscope counting cholinergic neurons. I would also like to thank Dr. Christine Werk for patiently reading and re-reading early drafts of my papers and this thesis and Dr.Hugo Lehmann for all his help in running statistics and interpreting my data. In addition, many thanks go out to Courtney Lamb, Robert Court and Arthur Verhoef for helping me with histology and behavioural testing, to Keri Colwell for running the corticosterone assays, the Metz lab for kindly allowing me the use of their microscope and to Karen Dow-Cazel and the rest of the animal care staff for taking care of my rats and helping me set up the circadian experiements. The cholinergic hypothesis of Alzheimer's disease 6 Acknowledgements IVThe basal forebrain cholinergic system 8The role of the basal forebrain cholinergic system in learning and memory 10The current state of the cholinergic hypothesis of Alzhimer's disease 15Risk factors for Alzheimer's disease 16Multiple combinations of co-factors theory of Alzheimer's disease 22The role of the hippocampus in learning and memory 24Objective of the present thesis 25Chapter 2: A series of pilot studies to determine the threshold for behaviourally sub threshold stroke, seizures and stress 28Abstract 29Experiment la: The effect of a chronic variable stress schedule on performance of the water maze task 32 Materials and Methods 33Results 36Experiment lb: The effects of a variable restraint stress procedure on levels of blood borne CORT 39 Materials and Methods 39Results 40Discussion 41Experiment 2: T...

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Lesions of the cholinergic nuclei in the rat basal forebrain: Excitotoxins vs. an immunotoxin

Cited by 40 publications

References 29 publications

Changes in electrocortical power and coherence in response to the selective cholinergic immunotoxin 192 IgG-saporin

Changes in electrocortical power and coherence in response to the selective cholinergic immunotoxin 192 IgG-saporin

Lesions of the nucleus basalis magnocellularis induced by 192 IgG-saporin block memory enhancement with posttraining norepinephrine in the basolateral amygdala

Revisiting the cholinergic hypothesis in the development of Alzheimer's disease

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