Intraseptal connections redefined: lack of a lateral septum to medial septum path

The integrity of the septohippocampal system is essential for memory formation and spatial behavior as well as for the electrical stability of the hippocampus. For many years it has been tacitly assumed or explicitly stated that the reciprocal septohippocampal loop is closed by a massive lateral septum-medial septum path. In the present study we reexamined the intraseptal connectivity with Phaseolus vulgaris leucoagglutinin tracing combined with choline acetyltransferase and parvalbumin immunohistochemistry at both the light and electron microscopic levels. We found that the previously hypothesized lateral septum to medial septum projection is extremely sparse and that the major medial septum to lateral septum path is parvalbumin-immunoreactive (likely GABAergic). The redefined circuitry has important implications for the understanding of the septal regulation of hippocampal electrical activity and the operations of the septo-hippocampal system.