Loss of nucleus basalis magnocellularis, but not septal, cholinergic neurons correlates with passive avoidance impairment in rats treated with 192-saporin.

Intraventricular injection of 192-saporin, an immunotoxin directed at the low affinity neurotrophin receptor (p75NGFr), selectively destroys cholinergic neurons in the basal forebrain (CBF). In the present study, we sought to determine if there was a correlation between degree of CBF neuron destruction and degree of passive avoidance behavioral impairment. 192-saporin caused a decrease in the number of p75NGFr + neurons in both nucleus basalis magnocellularis (Nbm) and medial septal nucleus/diagonal band of Broca (MS/DBB). All rats had >95% loss of the p75NGFr + cholinergic neurons in the MS/DBB, but there was variation in the extent of the Nbm cell loss. A significant correlation was found between the severity of impairment of passive avoidance learning and the magnitude of the loss in the number of p75NGFr + neurons in the Nbm. Step-through latency also correlated significantly with the magnitude of loss of AChE histochemical staining intensity in dorsolateral neocortex ipsilateral to the injection of 192-saporin. These data show that >95% loss of cholinergic neurons in MS/DBB is not sufficient to impair passive avoidance learning. However, in the presence of severe loss of cholinergic neurons from the MS/DBB, the resulting deficit in passive avoidance behavior is proportional to the degree of cholinergic neuron loss from the Nbm. These results are interpreted as support for the hypothesis that the cholinergic projection from Nbm to neocortex plays a role in passive avoidance behavior.