The GABAergic septohippocampal pathway in control and reeler mice: target specificity and termination onto Reelin-expressing interneurons

Abstract

The septohippocampal pathway contains two separate components: the cholinergic and the GABAergic. Whereas cholinergic fibers terminate on many hippocampal cell types, GABAergic septohippocampal fibers selectively contact the cell bodies of hippocampal interneurons. We examined whether the GABAergic septohippocampal system was altered in reeler mice. First, we found that both components of the septohippocampal pathway in mice present a distribution and target-cell specificity similar to that described in rats. We also show that GABAergic septohippocampal axons terminate on subpopulations of interneurons expressing reelin, which may implicate this extracellular matrix protein in the targeting of septohippocampal axons. We thus examined the septohippocampal pathway in reeler mice defective in Reelin. In contrast to wild-type animals, reeler mice displayed an ectopic location of both cholinergic and GABAergic fibers, which accumulate close to the hippocampal fissure. Despite their altered distribution, GABAergic septal axons maintain their target-cell selectivity innervating exclusively the perisomatic region of hippocampal interneurons. Thus, as in wild type, GABAergic septal fibers formed complex baskets around the cell body of GAD-positive hippocampal neurons in reeler mice. In addition, we found that reeler hippocampi have an altered distribution of hippocampal interneurons expressing PARV or CALB, many of which are located close to the hippocampal fissure. We thus conclude that although reeler mice have an altered distribution of hippocampal interneurons, GABAergic septohippocampal axons nevertheless terminate on their specific target interneurons. Thus, whereas target layer termination of septal fibers is severely impaired in reeler mice, our data indicate that the cell-specific targeting of GABAergic septohippocampal axons is governed by Reelin-independent signals.