Neurogenesis and regeneration in the primary olfactory pathway of mammals.

The primary sensory neurons in the olfactory and vomeronasal mucosae develop outside the neuraxis from ectodermal placodes, and their axons enter the central nervous system (CNS) during embryonic life, to terminate in the olfactory and accessory olfactory bulbs. The sensory neurons are unique in that they are produced and differentiate continuously from a stem cell in the sensory epithelium, throughout the life of the animal. After loss of sensory neurons following injury, the stem cell is able to increase its rate of division and replace the lost neurons. Sensory neurons thus formed during adult life, in the normal animal or after injury, possess another important and unique property: they are able to grow axons which can re-enter the CNS. Once in the CNS they can re-establish synaptic contact with central neurons. Such regenerative growth can result in re-establishment of connections between sensory mucosa and olfactory bulb in the adult animal, and a consequent recovery of olfactory function after injury to the pathway. However, a 'normal' pattern of connections is not always re-established, and olfactory axons may regenerate into areas of the CNS which they never enter during normal development. The special qualities which allow olfactory axons to re-enter the CNS are not known. Current work is aimed at examining more closely the interface where the peripheral nerve meets the CNS. Preliminary results suggest that this interface may be hard to define: the olfactory nerves themselves, although classically regarded as peripheral nerves, possess some features of central tracts, since their glia contain the astrocyte-specific protein GFAP, and resemble astrocytes in fine structure.