Nervus terminalis and nerves to the vomeronasal organ: a study using human fetal specimens

Abstract

The human nervus terminalis (terminal nerve) and the nerves to the vomeronasal organ (VNON) are both associated with the olfactory nerves and are of major interest to embryologists. However, there is still limited knowledge on their topographical anatomy in the nasal septum and on the number and distribution of ganglion cells along and near the cribriform plate of the ethmoid bone. We observed serial or semiserial sections of 30 fetuses at 7–18 weeks (crown rump length [CRL], 25–160 mm). Calretinin and S100 protein staining demonstrated not only the terminal nerve along the anterior edge of the perpendicular lamina of the ethmoid, but also the VNON along the posterior edge of the lamina. The terminal nerve was composed of 1–2 nerve bundles that passed through the anterior end of the cribriform plate, whereas the VNON consisted of 2–3 bundles behind the olfactory nerves. The terminal nerve ran along and crossed the posterior side of the nasal branch of the anterior ethmoidal nerve. Multiple clusters of small ganglion cells were found on the lateral surfaces of the ethmoid's crista galli, which are likely the origin of both the terminal nerve and VNON. The ganglions along the crista galli were ball-like and 15–20 µm in diameter and, ranged from 40–153 in unilateral number according to our counting at 21-µm-interval except for one specimen (480 neurons; CRL, 137 mm). An effect of nerve degeneration with increasing age seemed to be masked by a remarkable individual difference.

Expression of the ACE2 virus entry protein in the nervus terminalis reveals the potential for an alternative route to brain infection in COVID-19

“…Another argument to consider the nervus terminalis as an alternative to the olfactory route is that neuro-invasion in most animal models is highly variable, even in the same species and transgenic model (Jiang et al, 2020; Oladunni et al, 2020; Rathnasinghe et al, 2020; Winkler et al, 2020; Ye et al, 2020; Zheng et al, 2020; Zhou et al, 2020), and this is in contrast to the olfactory system that is consistent in terms of numbers of neurons, gene expression and projections. The nervus terminalis, on the other hand, is known for its large variability between individuals of the same species or even when comparing the right side with the left side of the same individual (Larsell, 1918; Jin et al, 2019). Such numerical differences can approach or even exceed an entire order of magnitude (Schwanzel-Fukuda et al, 1987; Jin et al, 2019) – and thus may explain the reported large variability in neuro-invasion (Butowt et al, 2021).…”

Identifying Isl1 Genetic Lineage in the Developing Olfactory System and in GnRH-1 Neurons

“…Neurogenic waves in the olfactory pit of mice first gives rise to mostly migratory neurons (Fornaro et al, 2003;Forni et al, 2013) such as early pioneer olfactory neurons, neurons of the terminal nerve, including Gonadotropin releasing hormone-1 neurons (GnRH-1ns), NPY positive migratory neurons, and other neurons with unknown identity and function or neurons of the migratory mass (MM) (Schwanzel-Fukuda and Pfaff, 1989;Wray et al, 1989;Hilal et al, 1996;Fornaro et al, 2007). The nasal area of mice contains several other neuronal cell types that include specialized olfactory sensory neurons (OSNs) such as the guanylyl cyclase-D (GC-D) neurons of the necklace olfactory system (Luo, 2008;Mori et al, 2014;Greer et al, 2016), microvillar cells (MVCs) (Pfister et al, 2012), sensory neurons of the septal organ (SO) (Ma et al, 2003), the Grueneberg ganglion (GG) (Gruneberg, 1973;Schmid et al, 2010;Mamasuew et al, 2011;Matsuo et al, 2012;Moine et al, 2018), and cells forming the terminal nerve ganglion (TN) (Larsell, 1950;Brown, 1987;Jennes, 1987;Oelschlager et al, 1987;Schwanzel-Fukuda et al, 1987;Wirsig-Wiechmann, 2004;Taroc et al, 2017;Jin et al, 2019) including the GnRH-1ns (Schwanzel-Fukuda and Pfaff, 1989;Wray et al, 1989). The mechanisms and molecules that drive progenitors of the developing olfactory pit into early migratory cells types remain largely unknown.…”

Expression of the ACE2 Virus Entry Protein in the Nervus Terminalis Reveals the Potential for an Alternative Route to Brain Infection in COVID-19

“…In humans, the number of nervus terminalis neurons is relatively small (a few hundred to a few thousand neurons depending on age, Brookover, 1917 ; Larsell, 1950 ; Jin et al, 2019 ). However, it is possible that such a relatively small number is sufficient to mediate viral infection.…”

“…Another argument to consider the nervus terminalis as an alternative to the olfactory route is that neuro-invasion in most animal models is highly variable, even in the same species and transgenic model ( Jiang et al, 2020 ; Oladunni et al, 2020 ; Rathnasinghe et al, 2020 ; Winkler et al, 2020 ; Ye et al, 2020 ; Zhou et al, 2020 ; Zheng et al, 2021 ), and this is in contrast to the olfactory system that is consistent in terms of numbers of neurons, gene expression and projections. The nervus terminalis, on the other hand, is known for its large variability between individuals of the same species or even when comparing the right side with the left side of the same individual ( Larsell, 1918 ; Jin et al, 2019 ). Such numerical differences can approach or even exceed an entire order of magnitude ( Schwanzel-Fukuda et al, 1987 ; Jin et al, 2019 )—and thus may explain the reported large variability in neuro-invasion ( Butowt et al, 2021 ).…”