The behavioral functions of the cholinergic basal forebrain: lessons from 192 IgG-saporin.
Until recently our understanding of the functional neuroanatomy of the cholinergic basal forebrain (CBF) has been hindered by the lack of a lesioning technique that is truly selective. The development of the immunotoxin 192 IgG-saporin (192-sap) has greatly improved our ability to create specific lesions of the CBF. Rats with such lesions have been studied in a wide variety of behavioral paradigms of learning, memory, and attention. Complete or near-complete destruction of the CBF results in deficits in a variety of behavior paradigms including passive avoidance, spatial tasks (water and radial mazes), delayed matching to position/sample, and attentional tasks. However, interpretation of many experiments is hampered by incomplete lesions and/or concomitant damage to cerebellar Purkinje neurons. Future studies will need to address these issues. Recent development of a similar immunotoxin that is effective in primates should permit more sophisticated behavioral analysis of CBF function. Additionally, immunotoxins selective for other types of neurons, such as the noradrenergic selective anti-DBH-saporin, will permit analysis of the behavioral functions of other diffusely projecting systems and how these other systems may interact with the CBF.
Wrenn
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Laboratory of Experimental Neurology, Department of Veterans Affairs, Nashville, TN 37212, USA.
Wiley
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RG
D000818:Animals; D000911:Antibodies, Monoclonal / Q000633:toxicity*; D001288:Attention / Q000187:drug effects*; D018678:Cholinergic Agents / Q000633:toxicity*; D000922:Immunotoxins / Q000633:toxicity*; D007276:Injections, Intraventricular; D007858:Learning / Q000187:drug effects*; D008568:Memory / Q000187:drug effects; D009699:N-Glycosyl Hydrolases; D016548:Prosencephalon / Q000187:drug effects*; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000276:immunology; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins
C085696:192 IgG-saporin; D000911:Antibodies, Monoclonal; D018678:Cholinergic Agents; D000922:Immunotoxins; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D054789:Ribosome Inactivating Proteins, Type 1; D009699:N-Glycosyl Hydrolases; D000076985:Saporins