The nervus terminalis (NT) is a cranial nerve connecting the peripheral olfactory structures with the brain. It enters the brain at the most anterior midline point, and is sometimes called """"""""called"""""""" """"""""cranial nerve zero"""""""". The NT nerve is present in all vertebrate groups, including humans and is the only cranial nerve of unknown function. Fibers and cells in the NT nerve and its ganglion contain LHRH (luteinizing-hormone releasing-hormone) a peptide that indirectly controls gonadal functions and, it now appears, also influences reproductive behavior of male and female rodents and other species. The NT nerve connects within the brain to a region concerned with reproductive control and there is evidence in mammals and fish that NT may influence reproductive behavior and physiology. Thus, NT may respond to chemical messengers from other individuals (pheromone) by delivering LHRH into the brain or the cerebral blood vessels. We are studying the NT nerve and ganglion in elasmobranch fish where it is a discrete entity and can thus be studied without interference from other neural structures. We have demonstrated that neural activity of cells in the ganglion is tonically suppressed by ganglion appear to be excited by acetyl choline and suppressed by norepinephrine. Indirect evidence suggests these are the LHRH cells, many of which send their axons centrally towards the brain. Preliminary evidence suggests some of these cells may be excited by neural input from the NT nerve connection with the nose. Another cell group, apparently containing a different peptide, is suppressed by acetyl choline and also projects centrally. We propose a tentative neural circuit for the NT ganglion and a working hypothesis for NT function: that the NT ganglion is an outpost of the forebrain LHRH network and serves as an interface for chemosensory influences on reproduction. Here we propose a tentative neural circuit for the NT ganglion and a working hypothesis for NT function: that the NT ganglion is an outpost of the forebrain suggested circuit (a)using tracer materials to label the projections to identified cell types in the ganglion and of sources of suppression in the brain; and (b) by recording responses of identified cells to neurotransmitter and neuropeptides and to neural input from central and peripheral nerve trunks. Further, the working hypothesis will be examined by testing the chemosensitivity of the system (a) to classes of chemicals known to act as pheromone in other fish and (b) by testing NT markers for chemoreceptive cells; The proposed release of LHRH (and other peptides) into the brain and cerebral circulation will be investigated by collecting medium in which the excised NT has been stimulated to release peptides in vitro, or by collecting blood and CSF after stimulation of the NT nerve in vivo. By these means we hope to identify the original function of a cranial nerve, present in humans, whose function is currently unknown and to demonstrate the circuits and neural mechanisms which underlie that function in our animal model.
