Development of the human olfactory system.

This chapter focuses on the development of the human olfactory system. In this system, function does not require full neuroanatomical maturity. Thus, discrimination of odorous molecules, including a number within the mother's diet, occurs in amniotic fluid after 28-30 weeks of gestation, at which time the olfactory bulbs are identifiable by MRI. Hypoplasia/aplasia of the bulbs is documented in the third trimester and postnatally. Interestingly, olfactory axons project from the nasal epithelium to the telencephalon before formation of the olfactory bulbs and lack a peripheral ganglion, but the synaptic glomeruli of the future olfactory bulb serves this function. Histologic lamination of the olfactory bulb is present by 14 weeks, but maturation remains incomplete at term for neuronal differentiation, synaptogenesis, myelination, and persistence of the normal transitory fetal ventricular recess. Myelination occurs postnatally. Although olfaction is the only sensory system without direct thalamic projections, the olfactory bulb and anterior olfactory nucleus are, in effect, thalamic surrogates. For example, many dendro-dendritic synapses occur within the bulb between GABAergic granular neurons and periglomerular neurons. Moreover, bulbar synaptic glomeruli are analogous to peripheral ganglia of other sensory cranial nerves. The olfactory tract contains much gray as well as white matter. The olfactory epithelium and bulb both incorporate progenitor cells at all ages. Diverse malformations of the olfactory bulb can be detected by clinical examination, imaging, and neuropathology; indeed, olfactory reflexes of the neonate can be reliably tested. We recommend that such testing be routine in the neonatal neurologic examination, especially in children with brain malformations, endocrinopathies, chromosomopathies, genetic/metabolic disorders, and perinatal hypoxic/ischemic encephalopathy.