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 (p75(NGFr)), selectively destro ys cholinergic neurons in the basal forebrain (CBF). In the present st udy, we sought to determine if there was a correlation between degree of CBF neuron destruction and degree of passive avoidance behavioral i mpairment. 192-Saporin caused a decrease in the number of p75(NGFr)+ n eurons in both nucleus basalis magnocellularis (Nbm) and medial septal nucleus/diagonal band of Broca (MS/DBB). All rats had >95% loss of th e p75(NGFr)+ cholinergic neurons in the MS/DBB, but there was variatio n in the extent of the Nbm cell loss. A significant correlation was fo und between the severity of impairment of passive avoidance learning a nd the magnitude of the loss in the number of p75(NGFr)+ neurons in th e Nbm. Step-through latency also correlated significantly with the mag nitude of loss of AChE histochemical staining intensity in dorsolatera l neocortex ipsilateral to the injection of 192-saporin. These data sh ow that >95% loss of cholinergic neurons in MS/DBB is not sufficient t o impair passive avoidance learning. However, in the presence of sever e loss of cholinergic neurons from the MS/DBB, the resulting deficit i n passive avoidance behavior is proportional to the degree of choliner gic neuron loss from the Nbm. These results are interpreted as support for the hypothesis that the cholinergic projection from Nbm to neocor tex plays a role in passive avoidance behavior.