GENETIC-VARIATION IN THE MORPHOLOGY OF THE SEPTOHIPPOCAMPAL CHOLINERGIC AND GABAERGIC SYSTEMS IN MICE .2. MORPHO-BEHAVIORAL CORRELATIONS

We investigated the contribution of the septo-hippocampal cholinergic and GABAergic system to spatial and nonspatial aspects of learning and memory that had previously been found to correlate with the extent of the hippocampal intra- and infrapyramidal messy fiber projection in d ifferent inbred mouse strains. The following cholinergic and GABAergic markers were measured in the septi and hippocampi of male mice: the n umber of cholinergic and parvalbumin-containing neurons in the medial septum/vertical limb of the diagonal band of Broca (MS/vDB), the numbe r of septo-hippocampal cholinergic and GABAergic projection neurons, t he density of cholinergic fibers in different hippocampal subfields, a nd the density of muscarinic receptors (predominantly M1 and M2) in th e hippocampus. In addition, animals were behaviorally tested for spati ally dependent and activity-dependent variables in a water maze and sp atial and nonspatial working and reference memory in different experim ental set-ups in an eight-arm radial maze. Using only those variables for which significant strain differences were obtained, we looked for covariations between behavior and neuroanatomy. The density of choline rgic fibers in the dentate gyrus was significantly correlated with act ivity-dependent learning in the water maze, whereas the number of sept o-hippocampal cholinergic projection neurons correlated with spatial a nd, to a lesser extent, also with nonspatial aspects of radial maze le arning. Only weak correlations were found between receptor densities a nd behavioral traits. From these data we conclude that variations in t he septo-hippocampal cholinergic system, like variations in the messy fiber projection, entail functional consequences for different types o f maze learning in mice. (C) 1996 Wiley-Liss, Inc.