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.