Neurogenetic and morphogenetic heterogeneity in the bed nucleus of the stria terminalis

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Abstract
Neurogenesis and morphogenesis in the rat bed nucleus of the stria terminalis (strial bed nucleus) were examined with [3H]thymidine autoradiography. For neurogenesis, the experimental animals were the offspring of pregnant females given an injection of [3H]thymidine on 2 consecutive gestational days. Nine groups of embryos were exposed to [3H]thymidine on E13–E14, E14–E15,…E21–E22, respectively. On P60, the percentage of labeled cells and the proportion of cells originating during 24‐hour periods were quantified at six anteroposterior levels in the strial bed nucleus. On the basis of neurogenetic gradients, the strial bed nucleus was divided into anterior and posterior parts. The anterior strial bed nucleus shows a caudal (older) to rostral (younger) neurogenetic gradient. Cells in the vicinity of the anterior commissural decussation are generated mainly between E13 and E16, cells just posterior to the nucleus accumbens mainly between E15 and E17. Within each rostrocaudal level, neurons originate in combined dorsal to ventral and medial to lateral neurogenetic gradients so that the oldest cells are located ventromedially and the youngest cells dorsolaterally. The most caudal level has some small neurons adjacent to the internal capsule that originate between E17 and E20. In the posterior strial bed nucleus, neurons extend ventromedially into the posterior preoptic area. Cells are generated simultaneously along the rostrocaudal plane in a modified lateral (older) to medial (younger) neurogenetic gradient. Ventrolateral neurons originate mainly between E13 and E16, dorsolateral neurons mainly between E15 and E16, and medial neurons mainly between E15 and E17. The youngest neurons are clumped into a medial “core” area just ventral to the fornix. For morphogenesis, pregnant females were given a single injection of [3H]thymidine during gestation, and their embryos were removed either 2 hours later (short survival) or in successive 24‐hour periods (sequential survival). The embryonic brains were examined to locate areas of intensely labeled cells in the putative neuroepithelium of the strial bed nucleus, to trace migratory waves of young neurons, and to establish their final settling locations. Two different neuroepithelial sources produce neurons for the strial bed nucleus. The anterior strial bed nucleus is generated by a neuroepithelial zone at the base of the inferior horn of the lateral ventricle from the anterior commissural decussation area forward to the primordium of the nucleus accumbens. The posterior strial bed nucleus is generated by a neuroepithelial zone at the base of the transient medial horn of the lateral ventricle, lateral to the fusion with the anterior thalamus. Neurons destined for the anterior strial bed nucleus migrate radially from their neuroepithelial source so that older neurons settle ventromedially, and younger neurons settle dorsolaterally, closest to the inferior horn. Older neurons destined for the lateral parts of the posterior strial bed nucleus migrate radially, reflecting the curve taken by the neuroepithelium in the medial horn. Younger neurons in the medial part also migrate radially, accumulating adjacent to the lateral neurons. The youngest neurons in the core and medial shell migrate ventromedially past older neurons and settle in clumps or diffusely throughout the medial part, Taken as a whole, these observations suggest that there is a developmental basis for the structural and functional hetero‐geneity found in the adult bed nucleus of the stria terminalis.