Development and topographic organization of subicular projections to lateral septum in the rat brain

• Published in: The European journal of neuroscience 2020-08, Vol.52 (4), p.3140-3159
• Main Authors: Tsamis, Konstantinos I., Lagartos Donato, Maria J., Dahl, Annelene G., O'Reilly, Kally C., Witter, Menno P.
• Format: Article
• Language: English
• Subjects: axonal development; Axonogenesis; Hippocampus; Innervation; Juveniles; neural circuits; postnatal development; Septum; Subiculum; Topography; Tracers; tracing
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/ejn.14696

One of the main subcortical targets of hippocampal formation efferents is the lateral septum. Previous studies on the subicular projections, as a main output structure of the hippocampus, have shown a clear topographic organization of septal innervation, related to the origin of the fibres along the dorsoventral axis of the subiculum in the adult brain. In contrast, studies on the developing brain depict an extensive rearrangement of subicular projections during the prenatal period, shifting from the medial septum to the lateral septum. Our study aimed to describe the postnatal development of subicular projections to the septum. We injected anterograde tracers into the subiculum of 57 pups of different postnatal ages. Injections covered the proximodistal and dorsoventral axis of the subiculum. The age of the pups at day of tracer injection ranged from the day of birth to postnatal day 30. Analyses revealed that from the first postnatal day projections from subiculum preferentially target the lateral septum. Sparse innervation in the lateral septum was already present in the first few postnatal days, and during the following 3 weeks, the axonal distribution gradually expanded. Subicular projections to the lateral septum are topographically organized depending on the origin along the dorsoventral axis of the subiculum, in line with the adult innervation pattern. Different origins along the proximodistal axis of the subiculum are reflected in changes in the strength of septal innervation. The findings demonstrate that in case of the development of subicular projections, axonal expansion is more prominent than axonal pruning. In the developing rat brain, subicular projections to the lateral septum are present from the first few postnatal days and they are topographically organized like in the adult. Fibres from subicular neurons situated at the dorsal part of the hippocampal formation innervate the dorsomedial part of lateral septum. Subicular fibres from progressively more ventral levels innervate progressively more lateral and ventral parts of lateral septum.