Olfactory Development, Part 1: Function, From Fetal Perception to Adult Wine-Tasting

Discrimination of odorous molecules in amniotic fluid occur after 30 weeks’ gestation; fetuses exhibit differential responses to maternal diet. Olfactory reflexes enable reliable neonatal testing. Olfactory bulbs can be demonstrated reliably by MRI after 30 weeks’ gestation, and their hypoplasia or aplasia also documented by late prenatal and postnatal MRI. Olfactory axons project from nasal epithelium to telencephalon before olfactory bulbs form. Fetal olfactory maturation remains incomplete at term for neuronal differentiation, synaptogenesis, myelination, and persistence of the transitory fetal ventricular recess. Immaturity does not signify nonfunction. Olfaction is the only sensory system without thalamic projection because of its own intrinsic thalamic equivalent. Diverse malformations of the olfactory bulb can be diagnosed by clinical examination, imaging, and neuropathology. Some epileptic auras might be primarily generated in the olfactory bulb. Cranial nerve 1 should be tested in all neonates and especially in patients with brain malformations, endocrinopathies, chromosomopathies, and genetic/metabolic diseases.

Olfactory Development, Part 2: Neuroanatomic Maturation and Dysgeneses

Olfactory axons project from nasal epithelium to the primitive telencephalon before olfactory bulbs form. Olfactory bulb neurons do not differentiate in situ but arrive via the rostral migratory stream. Synaptic glomeruli and concentric laminar architecture are unlike other cortices. Fetal olfactory maturation of neuronal differentiation, synaptogenesis, and myelination remains incomplete at term and have a protracted course of postnatal development. The olfactory ventricular recess involutes postnatally but dilates in congenital hydrocephalus. Olfactory bulb, tract and epithelium are repositories of progenitor stem cells in fetal and adult life. Diverse malformations of the olfactory bulb can be diagnosed by clinical examination, imaging, and neuropathologically. Cellular markers of neuronal differentiation and synaptogenesis demonstrate immaturity of the olfactory system at birth, previously believed by histology alone to occur early in fetal life. Immaturity does not preclude function.