Behavioral, biochemical, histological, and electrophysiological effects of 192 IgG-saporin injections into the basal forebrain of rats

Abstract

The behavioral, biochemical, histological, and electrophysiological effects of a basal forebrain injection of saporin, a ribosome-inactivating protein, coupled to a monoclonal antibody against the low-affinity NGF receptor (192 IgG) were investigated in adult rats. Within the basal forebrain region, the low-affinity NGF receptor is exclusively expressed by cholinergic neurons in the medial septal area, diagonal band, and nucleus basalis magnocellularis (NBM). The presence of this receptor upon these cells confers a degree of specificity to the 192 IgG-saporin that could not previously be achieved by previous lesioning techniques, such as excitatory amino acids. Rats with unilateral injections of different amounts of 192 IgG-saporin were prepared to determine the optimal conditions in order to produce a lesion restricted to the NBM that would not destroy cholinergic afferents to hippocampus or nearby regions. Electroencephalographic (EEG) recordings were taken from these lesioned rats before and during treatment with scopolamine (1 mg/kg, i.p.). Another group of rats received bilateral NBM injections of 192 IgG-saporin and were behaviorally tested using a rewarded, delayed-alternation task on a T-maze and a passive avoidance task. Finally, histological and biochemical investigations confirmed the effectiveness and specificity of the 192 IgG-saporin. The results showed that the 192 IgG-saporin did not destroy neurotensin, galanin, somatostatin, NADPH-diaphorase, or neuropeptide Y neurons within the NBM. Also, biomarkers of cholinergic function were significantly decreased throughout the neocortex and within the NBM, but not in the olfactory bulbs, hippocampus, or dorsal caudate nucleus. Intraperitoneal injections of scopolamine, but not NBM injections of 192 IgG-saporin, increased total power across all frequency bands; however, slow-wave frequencies showed a greater increase in power as compared to fast-wave frequencies. Acquisition, and performance of the delayed-alternation or passive avoidance tasks were not impaired by the lesions. These data confirm the effectiveness and specificity of this novel lesioning tool and suggest that selective loss of NBM cholinergic cells is not sufficient to impair performance in these behavioral tasks.