GENETICALLY-DETERMINED CHOLINERGIC DEFICIENCY IN THE FOREBRAIN OF C57BL 6 MICE/

This study demonstrates that a deficiency of forebrain cholinergic neu rons occurs in C57BL/6 (C57) mice, a strain characterized by poor lear ning capabilities. The brains of 21-day-old and 18-week-old C57 and DB A/2 (DBA) mice were studied by means of acetylcholinesterase (AChE) hi stochemistry and of choline acetyltransferase (ChAT) immunocytochemist ry. Computer-assisted image analysis was performed on sections through the medial septum, the diagonal band of Broca, the basal nucleus of M eynert and the neostriatum. As compared to the DBA strain, C57 mice ha d a reduced number of forebrain cholinergic neurons. This feature was present at the age of 21 days and persisted to 18 weeks. Between-strai n variations in the density of neurons were more obvious in ChAT-stain ed material than in AChE-stained sections. These data show that C57 mi ce can be regarded as a genetic mutant, whose phenotype is characteriz ed by a reduced number of forebrain cholinergic neurons and by cogniti ve abnormalities. C57 mice represent a valuable model for studying the influence of genetic factors on central nervous system cholinergic me chanisms and the effects of genetically determined cholinergic deficie ncy on behavior and learning.