Sexually dimorphic responses to neonatal basal forebrain lesions in mice: I. Behavior and neurochemistry

Abstract

The nucleus basalis magnocellularis (nBM) provides the primary source of cholinergic input to the cortex. Neonatal lesions of the nBM produce transient reductions in cholinergic markers, persistent abnormalities 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 tested at 8 weeks of age on a battery of behavioral tests including passive avoidance, cued and spatial tasks in the Morris water maze, simple and delayed nonmatch to sample versions of an odor discrimination task, and locomotor activity measurements. Following behavioral testing, mice were sacrificed for either morphological assessment or neurochemical analysis of a cholinergic marker or catecholamines. There were no lesion or sex differences in acquisition or retention of passive avoidance, performance of the odor discrimination tasks, or activity levels. Control mice showed a robust sex difference in performance of the spatial water maze task. The lesion produced a slight cued but more dramatic spatial navigation deficit in the water maze which affected only the male mice. Neurochemical analyses revealed no lesion‐induced changes in either choline acetyltransferase activity or levels of norepinephrine 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 development are responsible for the behavioral deficits seen in this study. © 1998 John Wiley & Sons, Inc. J Neurobiol 37: 582–594, 1998

Cholinergic Control in Developing Prefrontal–Hippocampal Networks

“…To avoid the influence of different maturation dynamics in males and females of the cholinergic system (Muñoz-Cueto et al, 1991;Arters et al, 1998), only male pups were used for all investigations. Immunohistochemical staining for ChAT performed at P0, P6, and P13 (n ϭ 18 pups) on coronal and sagittal sections including the PFC revealed the progressive densification of cholinergic axons with age.…”

Cholinergic Modulation of Spindle Bursts in the Neonatal Rat Visual CortexIn Vivo

“…For these investigations, only the male pups from three litters were used to avoid the influence of different maturation dynamic in males and females of the cholinergic system (Arters et al, 1998) in particular, and of the neocortex in general (Gregory, 1975;Munoz-Cueto et al, 1991). The pups were divided into three groups: (1) pups nontreated, serving as control (n ϭ 8), (2) pups receiving a bilateral intracerebroventricular injection of a total of 1 l of PBS (solvent for 192 IgG-saporin) at P0 (n ϭ 5), and (3) pups receiving a bilateral injection of a total of 1 l of 192 IgG-saporin (0.2 g/l) in PBS at P0 (n ϭ 8).…”

Cholinergic basal forebrain is critical for social transmission of food preferences

“…Frontoparietal cortex and hippocampus were dissected, weighed, frozen on dry ice, then stored at Ϫ70°C until the assay. Using the method of Fonnum (Fonnum, 1975), ChAT activity was determined by mea- suring the radiolabeled acetylcholine produced in brain homogenates from [ 14 C]acetyl coenzyme-A and choline, as described elsewhere (Arters et al, 1998). Protein content of the brain homogenates was determined by Bradford microtiter assay (Arters et al, 1998).…”