GENETIC-VARIATION IN THE MORPHOLOGY OF THE SEPTOHIPPOCAMPAL CHOLINERGIC AND GABAERGIC SYSTEM IN MICE .1. CHOLINERGIC AND GABAERGIC MARKERS

In the present study, variations of cholinergic and GABAergic markers in the medial septum/vertical limb of the diagonal band of Broca (MS/v DB) and the hippocampus of eight different inbred mouse strains were i nvestigated. By means of immunocytochemistry against the acetylcholine -synthesizing enzyme choline acetyltransferase (ChAT), the cholinergic neurons were visualized and the number of ChAT-positive neuronal prof iles in the MS/vDB was counted. Cholinergic and GABAergic septo-hippoc ampal projection neurons were detected with a combined retrograde trac ing and immunocytochemical approach. In order to quantify the choliner gic innervation of various hippocampal subregions, we estimated the de nsity of acetylcholinesterase (AChE)-containing fibers as visualized b y AChE histochemistry. Additionally, the densities of muscarinic recep tors (mainly the subtypes M1 and M2) in different hippocampal areas of seven inbred strains were measured by means of quantitative receptor autoradiography. We found significant strain differences for the numbe r of ChAT-positive neurons in the MS/vDB; in the numbers of cholinergi c septo-hippocampal projection neurons; in the density of cholinergic fibers in hippocampal subfields CA3c, CA1, and in the dentate gyrus; a nd in the density of muscarinic receptors in the hippocampus. In contr ast, the GABAergic component of the septo-hippocampal projection did n ot differ between the strains investigated. The number of ChAT-reactiv e neurons in the MS/vDB was not correlated with either hippocampal cho linergic markers. This might be attributed to different collateralizat ion of cholinergic neurons or to different projections of these neuron s to other brain regions. These results show a strong hereditary varia bility within the septo-hippocampal cholinergic system in mice. In vie w of the role of the cholinergic system in learning and memory process es, strain differences in cholinergic markers might be helpful in expl aining behavioral variation. (C) 1996 Wiley-Liss, Inc.