The fornix acts as a permissive corridor for septal neuron migration beyond the diencephalic-telencephalic boundary

Keisuke Watanabe,Noboru Sato,Hirohide Takebayashi

doi:10.1038/s41598-020-65284-7

Abstract

Neuronal migration is essential for constructing functional neural networks. Two posterior septal (PS) nuclei, the triangular septal nucleus and bed nuclei of the anterior commissure, are involved in fear and anxiety. During development, glutamatergic PS neurons undergo long-distance rostrodorsal migration from the thalamic eminence (TE) of the diencephalon, then settle in the caudalmost telencephalon. However, the developmental behavior of PS neurons and the guidance structures facilitating their migration remain unknown. We previously demonstrated the migration of PS neurons along the fornix, a major efferent pathway from the hippocampal formation. Here, we show that the postcommissural fornix is essential for PS neuron migration which is largely confined to its axonal tract, which grows in the opposite direction as PS neuron migration. Fornical axons reach the TE prior to initiation of PS neuron rostrodorsal migration. Ectopic expression of Semaphorin 3 A in the dorsomedial cortex resulted in defective fornix formation. Furthermore, loss of the postcommissural fornix stalled PS neuron migration resulting in abnormal accumulation near their origin. This suggests that PS neurons utilize the postcommissural fornix as a permissive corridor during migration beyond the diencephalic-telencephalic boundary. This axonal support is essential for the functional organization of the heterogeneous septal nuclear complex.

Highlights

Neuronal migration is essential for constructing functional neural networks
We previously demonstrated that posterior septal (PS) neurons migrate along the fornix by labeling a portion of the fornix using in utero electroporation (IUE)[6]
Cohorts of migrating PS neurons were largely confined to the L1-positive axon bundle of the postcommissural fornix, which projects from the subiculum to the mammillary nuclei (Fig. 1C’.ii, Fig. 1D’.ii, white arrowheads)[21,22]

Summary

Introduction

Neuronal migration is essential for constructing functional neural networks. Two posterior septal (PS) nuclei, the triangular septal nucleus and bed nuclei of the anterior commissure, are involved in fear and anxiety. Cohorts of migrating PS neurons were largely confined to the L1-positive axon bundle of the postcommissural fornix, which projects from the subiculum to the mammillary nuclei (Fig. 1C’.ii, Fig. 1D’.ii, white arrowheads)[21,22]. To observe individual neurons migrating toward the septal regions, we sparsely labeled PS neurons by IUE, in which the E12.5 TE was www.nature.com/scientificreports electroporated with a pCAG:EGFP (pCX-EGFP) plasmid (Fig. 2A)[6].

Results

Conclusion