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Reprint: Selective immunotoxic lesions of basal forebrain cholinergic cells: Effects on learning and memory in rats.
Baxter MG, Bucci DJ, Gorman LK, Wiley RG, Gallagher M (2013) Reprint: Selective immunotoxic lesions of basal forebrain cholinergic cells: Effects on learning and memory in rats. Behav Neurosci 127(5):619-627 . doi: 10.1037/a0033939
Summary: In this reprint of a 1995 article, 192-IgG-SAP (Cat. #IT-01) was used to separate the depletion of cortical cholineacetyltransferase and behavioral impairment – which had previously been linked by research using less specific lesioning methods. Since the original 1995 publication, hundreds of papers have been published using a variety of lesioning techniques and a wide range of ATS products.
Related Products: 192-IgG-SAP (Cat. #IT-01)
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Selective immunotoxic lesions of basal forebrain cholinergic neurons: twenty years of research and new directions.
Baxter MG, Bucci DJ (2013) Selective immunotoxic lesions of basal forebrain cholinergic neurons: twenty years of research and new directions. Behav Neurosci 127(5):611-618 . doi: 10.1037/a0033781
Summary: This review covers twenty years of basal forebrain cholinergic lesioning. The initial use of 192-IgG-SAP (Cat. #IT-01) is discussed, as well as other immunotoxins such as GAT-1-SAP (Cat. #IT-32) and OX7-SAP (Cat. #IT-02). The findings generated by the use of 192-IgG-SAP and how those data have helped forward the understanding of how the cholinergic system functions in the basal forebrain are detailed. The authors also discuss new directions in the field.
Related Products: 192-IgG-SAP (Cat. #IT-01), OX7-SAP (Cat. #IT-02), GAT1-SAP (Cat. #IT-32)
Neurotrophic factors rescue basal forebrain cholinergic neurons and improve performance on a spatial learning test.
Lee YS, Danandeh A, Baratta J, Lin CY, Yu J, Robertson RT (2013) Neurotrophic factors rescue basal forebrain cholinergic neurons and improve performance on a spatial learning test. Exp Neurol 249C:178-186. doi: 10.1016/j.expneurol.2013.08.012
Summary: It is thought that therapeutic treatments of the cholinergic system may be a viable treatment for Alzheimer’s disease. In order to examine this hypothesis the authors administered a total of 160 ng of 192-IgG-SAP (Cat. #IT-01) in the form of bilateral injections into the medial septum. The lesioned animals then received 4-week infusions of nerve growth factor, neurotrophin 3, or both into the lateral ventricles. Animals treated with any neurotrophin, either alone or as a combination, retained more ChAT-positive neurons and performed better on a delayed match-to-position task than control animals. The data strengthen the theory that exogenous neurotrophic factors ameliorate the effects of Alzheimer’s disease.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Cortical metabolic deficits in a rat model of cholinergic basal forebrain degeneration.
Gelfo F, Petrosini L, Graziano A, De Bartolo P, Burello L, Vitale E, Polverino A, Iuliano A, Sorrentino G, Mandolesi L (2013) Cortical metabolic deficits in a rat model of cholinergic basal forebrain degeneration. Neurochem Res 38(10):2114-2123. doi: 10.1007/s11064-013-1120-2
Summary: In this work the authors investigated the connection between cholinergic depletion caused by conditions such as Alzheimer’s disease and cerebral energy metabolism deficits. Rats received a 0.4-μg injection of 192-IgG-SAP (Cat. #IT-01) into the nucleus basalis magnocellularis. Neuronal metabolic activity was measured by assaying cytochrome oxidase (CO) activity. The unilateral injection produced a bilateral deficit in CO activity throughout the cortex, and the front and parietal cortices showed CO deficits before the lesion was complete. The data suggest a link between cholinergic hypofunctionality and metabolic deficit.
Related Products: 192-IgG-SAP (Cat. #IT-01)
An environment-dependent modulation of cortical neural response by forebrain cholinergic neurons in awake rat.
Ariffin MZ, Chang LS, Koh HC, Low CM, Khanna S (2013) An environment-dependent modulation of cortical neural response by forebrain cholinergic neurons in awake rat. Brain Res 1513:72-84. doi: 10.1016/j.brainres.2013.03.046
Summary: Rats received 168 ng of 192-IgG-SAP (Cat. #IT-01) into the medial septum and induction of c-Fos expression in response to either familiar or novel stimuli was measured.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Cholinergic basal forebrain structures are involved in the mediation of the arousal effect of noradrenaline.
Lelkes Z, Porkka-Heiskanen T, Stenberg D (2013) Cholinergic basal forebrain structures are involved in the mediation of the arousal effect of noradrenaline. J Sleep Res 22(6):721-726. doi: 10.1111/jsr.12061
Summary: Wakefulness is enhanced by the injection of noradrenaline into the basal forebrain, but it has not been clear whether cholinergic or non-cholinergic neurons are involved. 230 ng of 192-IgG-SAP (Cat. #IT-01) was administered to the horizontal diagonal band/substantia innominata/ magnocellular preoptic nucleus of rats. Upon treatment with methoxamine, lesioned animals lost the non-REM sleep-suppressing effect, but the REM sleep-suppressing effect remained intact.
Related Products: 192-IgG-SAP (Cat. #IT-01)
The role of visual cortex acetylcholine in learning to discriminate temporally modulated visual stimuli.
Minces VH, Alexander AS, Datlow M, Alfonso SI, Chiba AA (2013) The role of visual cortex acetylcholine in learning to discriminate temporally modulated visual stimuli. Front Behav Neurosci 7:16. doi: 10.3389/fnbeh.2013.00016
Summary: In order to examine some of the minor differences in the temporal structure of stimuli, the authors bilaterally injected 37.5 ng of 192-IgG-SAP (Cat. #IT-01) between the lambda and bregma of rats. This injection reduced acetylcholine projections to the visual cortex. Loss of that cholinergic input impaired the ability of the lesioned animals to perform fine discriminations, but previously learned discriminations remained unimpaired.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Long-term effects of selective immunolesions of cholinergic neurons of the nucleus basalis magnocellularis on the ascending cholinergic pathways in the rat: A model for Alzheimer’s disease.
Szigeti C, Bencsik N, Simonka AJ, Legradi A, Kasa P, Gulya K (2013) Long-term effects of selective immunolesions of cholinergic neurons of the nucleus basalis magnocellularis on the ascending cholinergic pathways in the rat: A model for Alzheimer’s disease. Brain Res Bull 94C:9-16. doi: 10.1016/j.brainresbull.2013.01.007
Summary: 192-IgG-SAP (Cat. #IT-01) has been used extensively to generate models of Alzheimer’s disease in rats. In this work, the authors detailed the time course of neuronal loss with an eye on potential recovery from the lesion. The nucleus basalis magnocellularis of rats was injected with 75 ng of 192-IgG-SAP (Cat. #IT-01) and long-term changes were tracked by immunohistochemistry. While some acetylcholinesterase neurons, considered cholinoceptive, were lost, choline acetyltransferase (cholinergic) neurons sustained a massive irreversible reduction in number.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Spatial memory facilitation by electrical stimulation of the medial septum in rats.
Jeong D, Lee J, Lee S, Kim S, Chang J (2012) Spatial memory facilitation by electrical stimulation of the medial septum in rats. Neuroscience 2012 Abstracts 851.01. Society for Neuroscience, New Orleans, LA.
Summary: Recently, deep brain stimulation has been used to treat various neurological disorders. Some studies support that DBS can be a strategy to treat Alzheimer’s disease. The aim of this study was to evaluate the effect of electrical stimulation in the medial septum using rat model mimicking basal forebrain cholinergic deficits of Alzheimer’s disease. Four experimental groups were composed of normal, lesion, lesion + implantation and lesion + stimulation. 192 IgG-saporin (Selective cholinergic toxin, 8ul of 0.63ug/ul) were bilaterally injected into the lateral ventricle. Electrode was stereotactically implanted into the left medial septum (AP +0.6, ML 0.16, DV -6). Stimulation parameters are 50Hz, 120us pulse width and 1 volt. One week after implantation, Stimulation started for 2 weeks. Two weeks after surgery, water maze was performed for 1 week and rats were sacrificed immediately after behavioral test. Features were verified by immunochemistry and AChE assay. During the training trials, latencies of lesion and implantation significantly increased in day3 and day4. In contrast, latency of stimulation group had no differences as compared to normal group but it decreased significantly when compared to lesion group in day4. In the probe test, lesion group had decreases in time in target quadrant, time in platform zone and the number of platform crossing. Although they did not perform as normal group, stimulation group showed tendency of recovery. IHC and AChE assay are ongoing. Spatial memory is associated with hippocampus. We had expected activation of hippocampus by stimulation of the medial septum. We confirmed that stimulation of the medial septum facilitates acquisition and recall of spatial memory. Currently we are studying the effects of medial septal stimulation on the hippocampus.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Cholinergic contributions to learned attentional suppression in the rat with touchscreens.
Ljubojevic V, Botly L, De Rosa E (2012) Cholinergic contributions to learned attentional suppression in the rat with touchscreens. Neuroscience 2012 Abstracts 729.13. Society for Neuroscience, New Orleans, LA.
Summary: One of the tasks of the attentional system is to filter environmental input according to its behavioral relevance. The neuromodulator acetylcholine (ACh) is thought to play a role in this process because of its ability to boost the signal-to-noise ratio of incoming sensory information. Cholinergic innervation of the attentional system has been shown to be necessary for successful selection of behaviorally-relevant stimuli (signal). However, it is not yet clear if ACh also plays a part in the attentional suppression of behaviorally-irrelevant information (noise). Thus, we examined the effect of cortical cholinergic deafferentation on attentional suppression in rats. To measure attentional suppression, we used a rat analog of the learning-to-ignore (LI) task originally designed for human participants (Dixon et al., 2009). The paradigm consisted of three stages of training (Prime1, Prime2, Probe; 10 sessions per stage), each of which involved stages of visual simultaneous discriminations between two stimuli. In both Prime conditions, individuals learned to respond to target stimuli (A+ and then C+ respectively), while ignoring the same distractor stimulus (B-). During Probe, the previously ignored stimulus became the target (B+) and a novel stimulus (D-) was introduced as a distractor. Eighteen male Long-Evans rats were trained to perform the touchscreen-based LI task. Like the human data, a behavioral decrement (lower accuracy) was observed during the Probe phase of the LI task when compared to Prime 1 and 2, which suggests that the ignored distractor stimulus was suppressed during Prime. We hypothesized that administration of the ACh-specific immunotoxin, 192 IgG-saporin, into the nucleus basalis magnocellularis (NBM) would lead to better performance during Probe condition relative to controls. Accordingly, the rats were subjected to either cholinergic immunotoxic (SAP, N=10) or sham lesion surgery (SHAM, N=8). After 2 weeks of post-surgical recovery, the rats were tested on the LI task with a new stimulus set. The two groups performed comparably during Prime1 and 2, with both SAP and SHAM rats successfully learning the discriminations. As predicted, during Probe SAP rats exhibited significantly less behavioral decrement than controls. Histological analysis revealed that the lesion was chemically and anatomically specific to cholinergic cells in the NBM. This counterintuitive finding suggests that the improved performance during Probe, due to reduced ACh input to the neocortex, was due to inefficient attentional suppression of the behaviorally-irrelevant stimulus.
Related Products: 192-IgG-SAP (Cat. #IT-01)