Critical test of the assumption that the hypothalamic entopeduncular nucleus of rodents is homologous with the primate internal pallidum

The globus pallidus (GP) of primates is divided conventionally into distinct internal and external parts. The literature repeats since 1930 the opinion that the homolog of the primate internal pallidum in rodents is the hypothalamic entopeduncular nucleus (embedded within fiber tracts of the cerebral peduncle). To test this idea, we explored its historic fundaments, checked the development and genoarchitecture of mouse entopeduncular and pallidal neurons, and examined relevant comparative connectivity data. We found that the extratelencephalic mouse entopeduncular structure consists of four different components arrayed along a dorsoventral sequence in the alar hypothalamus. The ventral entopeduncular nucleus (EPV), with GABAergic neurons expressing Dlx5 & 6 and Nkx2-1, lies within the hypothalamic peduncular subparaventricular area. Three other formations-the dorsal entopeduncular nucleus (EPD), the prereticular entopeduncular nucleus (EPPRt), and the preeminential entopeduncular nucleus (EPPEm)-lie within the overlying paraventricular area, under the subpallium. EPD contains glutamatergic neurons expressing Tbr1, Otp, and Pax6. The EPPRt has GABAergic cells expressing Isl1 and Meis2, whereas the EPPEm population expresses Foxg1 and may be glutamatergic. Genoarchitectonic observations on relevant areas of the mouse pallidal/diagonal subpallium suggest that the GP of rodents is constituted as in primates by two adjacent but molecularly and hodologically differentiable telencephalic portions (both expressing Foxg1). These and other reported data oppose the notion that the rodent extratelencephalic entopeduncular nucleus is homologous to the primate internal pallidum. We suggest instead that all mammals, including rodents, have dual subpallial GP components, whereas primates probably also have a comparable set of hypothalamic entopeduncular nuclei. Remarkably, there is close similarity in some gene expression properties of the telencephalic internal GP and the hypothalamic EPV. This apparently underlies their notable functional analogy, sharing GABAergic neurons and thalamopetal connectivity. Various molecular and hodological data illustrate external and internal parts of the mouse globus pallidus, comparable to those in primates, whereas the distant hypothalamic entopeduncular population shows independent dorsal and ventral parts. The conventional hypothesis that the rodent entopeduncular nucleus is homologous to the primate internal pallidus is therefore inconsistent.image

Automated summary

This study reveals that the internal pallidum in rodents is not homologous to the globus pallidus (GP) in primates, but rather has independent dorsal and ventral parts. On the other hand, both rodents and primates have similar gene expression properties and connectivity between their respective pallidal and hypothalamic structures. This finding is important for understanding the function and evolution of these structures in different species.