Serotonin and urocortin 1 in the dorsal raphe and Edinger-Westphal nuclei after early life stress in serotonin transporter knockout rats.

The interaction of early life stress (ELS) and the serotonin transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR) has been associated with increased risk to develop depression in later life. We have used the maternal separation paradigm as a model for ELS exposure in homozygous and heterozygous 5-HTT knockout rats and measured urocortin 1 (Ucn1) mRNA and/or protein levels, Ucn1 DNA methylation, as well as 5-HT innervation in the centrally projecting Edinger-Westphal (EWcp) and dorsal raphe (DR) nuclei, both implicated in the regulation of stress response. We found that ELS and 5-HTT genotype increased the number of 5-HT neurons in specific DR subdivisions, and that 5-HTT knockout rats showed decreased 5-HT innervation of EWcp-Ucn1 neurons. Furthermore, ELS was associated with increased DNA methylation of the promoter region of the Ucn1 gene and increased expression of 5-HT receptor 1A in the EWcp. In contrast, 5-HTT deficiency was associated with site-specific alterations in DNA methylation of the Ucn1 promoter, and heterozygous 5-HTT knockout rats showed decreased expression of CRF receptor 1 in the EWcp. Together, our findings extend the existing literature on the relationship between EWcp-Ucn1 and DR-5-HT neurons. These observations will further our understanding on their potential contribution to mediate affect as a function of ELS interacting with 5-HTTLPR.

Development of the human oculomotor nuclear complex: Centrally-projecting Edinger-Westphal nucleus.

BACKGROUND: The cytoarchitecturally defined Edinger-Westphal nucleus (EW) is now referred to by many investigators as the centrally-projecting EW (EWcp) in humans. Although the mature structure is well-characterized, there have been few reports describing the precise morphology of this nucleus during the second half of gestation. SUBJECTS/DESIGN: Eleven brains were examined from preterm infants, aged 20-39 postmenstrual weeks, who died of various causes. After fixation, the brains were embedded in celloidin and serial sections of 30-µm thickness were cut in the horizontal plane. Sections were stained using the Klüver-Barrera method. In addition to microscopic observations, computerized 3D reconstruction and morphometry were performed. RESULTS: From 21 weeks, the EWcp had a distinctive, complex 3D structure comprising two or three parts. The dorsal part was arcuate, half encircling the oculomotor somatic nuclei (OSN). The rostral part was the most voluminous, ventral to the rostral OSN, extending anteriorly. The caudal part was the smallest, and was composed of several neuronal groups near the ventral tip of the OSN. In three cases, the caudal part was absent. It could also be joined to the rostral part, forming a ventral part. The total volume of the EWcp increased exponentially with age, and the ventral part grew more rapidly than the dorsal part. The mean neuronal profile area increased linearly with age, and the rate of increase was almost equal between the dorsal and ventral parts. CONCLUSIONS: This study suggests that a distinctive, complex, two- or three-part 3D structure of the EWcp is preserved after mid-gestation, and that the ventral part of the EWcp may expand in volume more rapidly than the dorsal part.

Scaling the primate lateral geniculate nucleus: niche and neurodevelopment in the regulation of magnocellular and parvocellular cell number and nucleus volume.

New stereological assessments of lateral geniculate nucleus (LGN) neuron numbers and volumes in five New World primates (Cebus apella, Saguinus midas niger, Alouatta caraya, Aotus azarae, and Callicebus moloch) and compiled LGN volumes for an additional 26 mammals were analyzed for a better understanding of visual system evolution. Both the magnocellular (M)- and the parvocellular (P)-cell populations scale allometrically with brain volume in primates, P cells with a significantly higher slope such that, for every increase in M neuron number, P neuron numbers more than double (ln scale; y = 0.89x + 2.42R(2) = 0.664). In diurnal primates, the ratio of P to M cells was slightly but significantly higher than in nocturnal primates. For all mammals, including primates, LGN volume was unrelated to nocturnal or diurnal niche but showed marked differences in slope and intercept depending on taxonomic group. The allometric scaling of M and P cells can be related to the order of neurogenesis, with late-generated P cells increasing with positive allometry compared with the earlier-generated M cells. This developmental regularity links relative foveal representation to relative isocortex enlargement, which is also generated late. The small increase in the P/M cell ratio in diurnal primates may result from increased developmental neuron loss in the M-cell population as it competes for limited termination zones in primary visual cortex.