Effects of Selective Immunotoxic Lesions on Learning and Memory

Immunotoxins provide the opportunity to make neurotoxic lesions of specific neurochemically-defined neuronal populations (see Chapter 17) by targeting cell-surface antigens that are uniquely expressed by the cells of interest. The greatest application of these toxins in the study of learning and memory has been through the use of one specific immunotoxin, 192 IgG-saporin, which kills neurons that express the low-affinity nerve growth factor (NGF) receptor (1 , 2 ). The low-affinity NGF receptor (sometimes referred to as the p75 neurotrophin receptor) within the central nervous system is expressed by neurons in the basal forebrain and by cerebellar Purkinje cells (3 –5 ). Within the basal forebrain, this receptor is expressed only on cholinergic neurons (6 ). Therefore, when this toxin is injected into the basal forebrain, it produces selective lesions of cholinergic neurons, sparing noncholinergic neurons at the lesion site (7 ). This lesion method has been employed to create an animal model of the degeneration of basal forebrain cholinergic neurons seen in patients with Alzheimer’s disease (8 ). Such a model has been impossible to achieve with other lesion methods that do not produce selective damage to basal forebrain cholinergic neurons, limiting the interpretation of behavioral deficits observed after such lesions.