SEXUALLY DIMORPHIC RESPONSES TO NEONATAL NASAL FOREBRAIN LESIONS IN MICE - 1 - BEHAVIOR AND NEUROCHEMISTRY

The nucleus basalis magnocellularis (nBM) provides the primary source of cholinergic input to the cortex. Neonatal lesions of the nBM produc e transient reductions in cholinergic markers, persistent abnormalitie s in cortical morphology, and spatial navigation impairments in adult mice, The present study examined sex differences in the effects of an electrolytic nBM lesion on postnatal day 1 (PND 1) in mice on behavior and neurochemistry in adulthood. Mice were lesioned on PND 1 and test ed at 8 weeks of age on a battery of behavioral tests including passiv e avoidance, cued and spatial tasks in the Morris water maze, simple a nd delayed nonmatch to sample versions of an odor discrimination task, and locomotor activity measurements. Following behavioral testing, mi ce were sacrificed for either morphological assessment or neurochemica l analysis of a cholinergic marker or catecholamines. There were no le sion or sex differences in acquisition or retention of passive avoidan ce, performance of the odor discrimination tasks, or activity levels. Control mice showed a robust sex difference in performance of the spat ial water maze task. The lesion produced a slight cued but more dramat ic spatial navigation deficit in the water maze which affected only th e male mice, Neurochemical analyses revealed no lesion-induced changes in either choline acetyltransferase activity or levels of norepinephr ine or serotonin at the time of testing. The subsequent report shows a sex difference in lesion-induced changes in cortical morphology which suggests that sexually dimorphic cholinergic influences on cortical d evelopment are responsible for the behavioral deficits seen in this st udy. (C) 1998 John Wiley & Sons, Inc.