Abstract
Septal nuclei are telencephalic structures associated with a variety of brain functions as part of the limbic system. The two posterior septal nuclei, the triangular septal nucleus (TS) and the bed nuclei of the anterior commissure (BAC), are involved in fear and anxiety through their projections to the medial habenular nucleus. However, the development of both the TS and BAC remains unclear. Here, we found a novel caudal origin and putative migratory stream of mouse posterior septal neurons arising from the thalamic eminence (TE), a transient developmental structure at the rostral end of the rodent diencephalon. TE-derived cells, which have glutamatergic identity, migrated rostrally and entered the telencephalic territory by passing beneath the third ventricle. Subsequently, they turned dorsally toward the posterior septum. We also observed that TS and BAC neurons in the postnatal septum were labeled with GFP by in utero electroporation into the TE, suggesting a shared origin. Furthermore, TE-derived septal neurons migrated along the fornix, an efferent pathway from the hippocampus. These results demonstrate that posterior septal neurons have a distinct extratelencephalic origin from other septal nuclei. This heterogeneous origin may contribute to neuronal diversity of the septal nuclear complex.
Highlights
The septum, considered part of the limbic system, is composed of the subcortical telencephalic structures that lie close to the midline and anterior to the lamina terminalis
We confirmed that CalR mRNA was highly expressed in both the triangular septal nucleus (TS) and bed nuclei of the anterior commissure (BAC), which are located at the midline of the subcortical regions and are bilaterally adjacent to the anterior commissure, respectively, at the posterior level of the septal nuclei (Fig. 1A,B)
In sagittal sections of the adult brain, the TS was observed between two axonal tracts, the fornix and ventral hippocampal commissure, and the BAC was situated between the anterior commissure and fornix[29] (Fig. 1C)
Summary
The septum (septal nuclei), considered part of the limbic system, is composed of the subcortical telencephalic structures that lie close to the midline and anterior to the lamina terminalis. The MS and LS are rich in GABAergic neurons[1,13,14], whereas the TS is enriched with glutamatergic neurons[15,16] Both TS and BAC neurons express high levels of Vglut[2], which is mainly expressed in excitatory neurons of the diencephalic and brain stem regions[17]. These observations suggest that the posterior septal neurons are generated from an extra-telencephalic source, such as the neuroepithelium of the diencephalon. It was revealed that lot cells, which guide axons of the lateral olfactory tract, originate in the lateral part of the TE26 These studies indicate that TE-derived cells travel a long distance and differentiate into various neurons in diverse areas of the forebrain. Our findings indicate that the heterogeneous developmental origins of septal neurons may contribute to the neuronal diversity and functions of the septal nuclei
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