targeted-toxins

Berger-Sweeney J, Stearns NA, Frick KM, Beard B, Baxter MG (2000) Cholinergic basal forebrain is critical for social transmission of food preferences. Hippocampus 10(6):729-738. doi: 10.1002/1098-1063(2000)10:6<729::AID-HIPO1010>3.0.CO;2-M PMID: 11153718

Objective: To examine whether the cholinergic basal forebrain plays a role in non-spatial associative memory, specifically, the social transmission of food preferences.

Summary: The authors lesioned rats with 192-IgG-SAP to create selective lesions of basal forebrain cholinergic neurons and examine the rats ability to recall learned social food preference. It was shown that this type of memory was strongly associated with cholinergic activity and implicates the cholinergic projection to the neocortex in the formation of social memories.

Usage: Rats were subjected to 192 IgG-SAP (IT-01) injections at 0.175 mg/ml spread across the medial septum and vertical limb of the diagonal band of Broca bilaterally for a total of 2 microliters.

Related Products: 192-IgG-SAP (Cat. #IT-01)

Turchi J, Sarter M (2000) Cortical cholinergic inputs mediate processing capacity: Effects of 192 IgG-saporin-induced lesions on olfactory span performance. Eur J Neurosci 12:4505-4514.

Summary: Many experiments support the theory that the basal forebrain (BF) is involved in major aspects of attention that influence learning and memory. Elimination of cholinergic neurons in the BF by 192-Saporin (Cat. #IT-01) has been shown to reduce the ability of rats to perform a task while paying attention to more than one thing. The authors tested the treated rat’s ability to identify one olfactory stimuli from an increasing amount of such stimuli. While the performance of the treated rats returned to control levels within four weeks post-lesion, their performance reflected increased time between tests. These data indicate that cholinergic neurons of the BF play a role in attentional capacities.

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Villa AEP, Tetko IV, Dutoit P, Vantini G (2000) Non-linear cortico-cortical interactions modulated by cholinergic afferences from the rat basal forebrain. BioSystems 58:219-228. doi: 10.1016/s0303-2647(00)00126-x

Summary: Elimination of the cholinergic neurons of the basal forebrain (BF) is an excellent model for some aspects of Alzheimer’s Disease (AD). 192-Saporin (Cat. #IT-01) is a very effective tool for elimination of cholinergic neurons in the BF. Villa et al. investigate whether field potential changes in the brains of lesioned animals mimic changes observed in the brains of human AD patients. The data presented indicate depletion of cholinergic neurons from the BF of both rats and humans produces similar changes in field potential.

Related Products: 192-IgG-SAP (Cat. #IT-01)

Haas CA, Hollerbach E, Deller T, Naumann T, Frotscher M (2000) Up-regulation of growth-associated protein 43 mRNA in rat medial septum neurons axotomized by fimbria-fornix transection. Eur J Neurosci 12:4233-4242. doi: 10.1046/j.0953-816x.2000.01329.x

Summary: Axonal growth and regeneration is limited in adult mammals, however, if injured CNS neurons are in an environment permissive for growth, they can regenerate. Transection of septohippocampal fibers is a widely used method for studying CNS neuron response to injury. These fibers are composed of both cholinergic and GABAergic neurons. Haas et al. used a combination of cholinergic lesioning by 192-Saporin (Cat. #IT-01) and double staining to investigate whether both cell types were involved in neuron regeneration. The findings show that both transmitter phenotypes up-regulate mRNA levels of a protein associated with growth and synaptogenesis in developing neurons, and plasticity in adult neurons.

Related Products: 192-IgG-SAP (Cat. #IT-01)

Pain L, Jeltsch H, Lehmann O, Lazarus C, Laalou FZ, Cassel JC (2000) Central cholinergic depletion induced by 192 IgG-saporin alleviates the sedative effects of propofol in rats. Brit J Anaesth 85(6):869-873. doi: 10.1093/bja/85.6.869

Summary: In order to examine the effect of cholinergic depletion on the sedative potency of propofol in rats the authors injected 1 µg of 192-Saporin (Cat. #IT-01) into each lateral ventricle. The findings indicate a ~50% reduction in sedative potency in lesioned rats.

Related Products: 192-IgG-SAP (Cat. #IT-01)

Llewellyn-Smith IJ, Martin CL, Arnolda LF, Minson JB (2000) Tracer-toxins: cholera toxin B-saporin as a model. J Neurosci Methods 103(1):83-90. doi: 10.1016/s0165-0270(00)00298-3 PMID: 11074098

Related Products: CTB-SAP (Cat. #IT-14), Cholera Toxin B, Recombinant (Cat. #PR-14)

Wiley RG, Kline IV RH (2000) Neuronal lesioning with axonally transported toxins. J Neurosci Methods 103:73-82. doi: 10.1016/S0165-0270(00)00297-1

Summary: Functional neuroanatomy studies have long utilized lesioning. Given the complexity of heterogeneous neuron populations conventional lesioning methods have proved relatively crude, and have provided limited information. Wiley and Kline detail some of the immunotoxins utilizing saporin as well as neuropeptide-saporin conjugates that have found use in recent neurological research. These products include SP-SAP (Cat. #IT-07), which eliminates neurons expressing the neurokinin 1 receptor, 192-Saporin (Cat. #IT-01), which eliminates neurons expressing the p75 receptor in rats, anti-DBH-SAP (Cat #IT-03), which destroys noradrenergic and adrenergic neurons, and OX7-SAP (Cat. #IT-02), which is a suicide transport agent targeting all rat neurons. The authors also discuss some of the protocols and methods utilized with these compounds.

Related Products: 192-IgG-SAP (Cat. #IT-01), OX7-SAP (Cat. #IT-02), Anti-DBH-SAP (Cat. #IT-03), SP-SAP (Cat. #IT-07)

Sarter M, Turchi J (2000) Effects of intra-basalis infusion of d-cycloserine upon sustained attention performance in rats. Neuroscience 2000 Abstracts 837.10. Society for Neuroscience, New Orleans, LA.

Summary: As basal forebrain NMDA receptor modulation has been hypothesized to play a significant role in tasks taxing attentional processes (Turchi & Sarter 1999), positive NMDA receptor modulation via the glycine site might attenuate the substantive impairments of sustained attentional processing observed following specific lesions of corticopetal cholinergic neurons (McGaughy, Kaiser & Sarter, 1996). Rats were trained in a sustained attention task (McGaughy & Sarter 1995) requiring animals to discriminate between unpredictably occurring visual signals of varying lengths (25, 50, 500 msec) and non-signal events. Upon attaining stable performance, chronic guide cannula were implanted bilaterally for the infusion of an NMDA receptor glycine site ligand into the SI/NB; one group of these animals also received bilateral infusions of 192 IgG-saporin (0.21μg/μl; 0.5 μl/hemisphere), while the other group received infusions (0.5 μl/hemisphere) of the vehicle for the immunotoxin. The effects of administrations of D-cycloserine (DCS: 0.5 & 5 μg in 0.5 μl/hemisphere) were tested in these two groups of animals (lesioned and sham-lesioned). Administration of the higher dose of DCS partly attenuated the lesion-induced decrease in hits in the sustained attention paradigm. This finding suggests that impairments of sustained attention incurred by damage to the basal forebrain cholinergic system may be effectively ameliorated by positive NMDA receptor modulation via the partial agonism of the glycine site.

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Westhead C, Saari RK, Morrison P, Williams PT, Saari MJ (2000) Nucleus basalis magnocellularis and enriched housing: Partners in neural patterns of attention?. Neuroscience 2000 Abstracts 837.3. Society for Neuroscience, New Orleans, LA.

Summary: Diminished levels of cholinergic markers in the brains of Alzheimer’s patients led to the belief that central cholinergic systems play a major role in cognitive processes including attention and memory. Recent evidence from our laboratory suggests that housing rats in a complex environment alters neuronal attentional circuitry. These findings led to the design of the current experiment. After weaning, groups of female Wistar rats received either a bilateral infusion of 192-IgG saporin or vehicle solution into the basal forebrain. Following recovery, rats were either housed in an enriched condition or in isolated housing for two weeks, thus creating four treatment groups. Open field testing revealed the expected Housing by Minute interaction but no lesion related effects. The rats were also tested in an incidental learning paradigm. Briefly, half of the rats were pre-exposed to the testing apparatus in the testing room, whereas the other half were placed in a similar arena but in a separate room without task-specific cues. Analysis of the results revealed a significant interaction between the lesion and housing condition as a function of the pre-exposure. As expected, pre-exposure facilitated learning for all sham operated rats but the lesioned enriched rats performed in a paradoxical manner. These rats appeared to be confused by the pre-exposure to the testing apparatus. The findings suggest an inability of enriched lesioned subjects to distinguish between behaviourally relevant and irrelevant stimuli and are in general agreement with the findings of Kilgard and Merzenich (1998). (Approved by the Animal Care Committee, Nipissing University).

Related Products: 192-IgG-SAP (Cat. #IT-01)

Gill TM, Yurrita MM, Givens B (2000) Attentional demand-related alterations in medial prefrontal neural activity of aged rats during sustained visual attention. Neuroscience 2000 Abstracts 837.6. Society for Neuroscience, New Orleans, LA.

Summary: Neural activity within the medial prefrontal cortex (mPFC) exhibits distinct relationships to sustained visual attentional performance in young male Long-Evans rats. Cortical cholinergic input substantially modulates attentional performance, mPFC neural activity, and attentional-demand related alterations in mPFC neural activity. The present study sought to investigate the relationship between sustained attention, mPFC neural activity, and cholinergic input within aged rats. Rats were operantly trained to discriminate between the presence and absence of brief, unpredictable visual signals under testing conditions that varied the level of attentional demand by the presence of a visual distractor. Aged rats were bilaterally implanted with pairs of stereotrodes into the mPFC at 25 months. The overall firing rate of mPFC units recorded during sustained attention was higher in the aged rats (2.39 spikes/s) relative to young rats (1.65 spikes/s). Moreover, a larger percentage of mPFC units exhibited attentional demand-related increases or decreases in firing rate in the aged rats (29%) relative to young rats (18%). Conversely, the magnitude of attentional demand-related increases in activity was smaller in the aged rats (64% increase) relative to young rats (81% increase). The modulatory role of cortical cholinergic input on the overall firing and attentional demand-related alterations in mPFC activity will also be determined and contrasted to the effects in young rats using 192 IgG-saporin infusions into the mPFC.

Related Products: 192-IgG-SAP (Cat. #IT-01)