The terminal nerve and its relation with extrabulbar "olfactory" projections: lessons from lampreys and lungfishes.

The definition of the terminal nerve has led to considerable confusion and controversy. This review analyzes the current state of knowledge as well as diverging opinions about the existence, components, and definition of terminal nerves or their components, with emphasis on lampreys and lungfishes. I will argue that the historical terminology regarding this cranial nerve embraces a definition of a terminal nerve that is compatible with its existence in all vertebrate species. This review further summarizes classical and more recent anatomical, developmental, neurochemical, and molecular evidence suggesting that a multitude of terminalis cell types, not only those expressing gonadotropin-releasing hormone, migrate various distances into the forebrain. This results in numerous morphological and neurochemically distinct phenotypes of neurons, with a continuum spanning from olfactory receptor-like neurons in the olfactory epithelium to typical large ganglion cells that accompany the classical olfactory projections. These cell bodies may lose their peripheral connections with the olfactory epithelium, and their central projections or cell bodies may enter the forebrain at several locations. Since "olfactory" marker proteins can be expressed in bona fide nervus terminalis cells, so-called extrabulbar "olfactory" projections may be a collection of disguised nervus terminalis components. If we do not allow this pleiomorphic collection of nerves to be considered within a terminal nerve framework, then the only alternative is to invent a highly species- and stage-specific, and, ultimately, thoroughly confusing nomenclature for neurons and nerve fibers that associate with the olfactory nerve and forebrain.