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Year : 2020  |  Volume : 69  |  Issue : 1  |  Page : 53-56

Nervi terminalis (“0” pair of cranial nerve) revisited from fishes to humans

1 Department of Paedodontics and Preventive Dentistry, Santosh Dental College, Santosh Deemed to be University, NCR-Delhi, New Delhi, India
2 Medicine and Life Sciences, Springer Nature, New Delhi, India
3 Department of Anatomy KMC Manglore, MAHE Manipal, Karnataka, India

Date of Submission11-Jan-2020
Date of Acceptance18-Feb-2020
Date of Web Publication11-Apr-2020

Correspondence Address:
Dr. Vishram Singh
OC-5/103, 1st Floor, Orange County Society, Ahinsa Khand-I, Indirapuram, Ghaziabad, Delhi - 201 014
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/JASI.JASI_2_20

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According to classical teaching in medical colleges and institutes, there are 12 pairs of cranial nerves, attached to the brain. They are numbered in Roman numerals from I to XII in the craniocaudal order of their attachment on the brain. In fact, there are 13 pairs of cranial nerves, the one which is not taught is the nervus terminalis (NT), i.e., “0” pair of cranial nerve. It is attached rostral to all other cranial nerves. Although it has been clearly identified as an additional nerve in the vertebrate species including humans for more than a century, its functional role is also understood to some extent. Still, it could not find its place in the standard textbooks of anatomy. It has also been given different names, viz., nerve of Pinkus, NT, cranial nerve “0,” cranial nerve nulla, terminal nerve, and cranial nerve XIII.

Keywords: Crania nerve XIII, cranial nerve “0,” gonadotropin-releasing hormone, luteinizing hormone-releasing hormone, nervus terminalis, pheromones, reproductive behavior

How to cite this article:
Singh R, Singh G, Singh V. Nervi terminalis (“0” pair of cranial nerve) revisited from fishes to humans. J Anat Soc India 2020;69:53-6

How to cite this URL:
Singh R, Singh G, Singh V. Nervi terminalis (“0” pair of cranial nerve) revisited from fishes to humans. J Anat Soc India [serial online] 2020 [cited 2023 Feb 4];69:53-6. Available from: https://www.jasi.org.in/text.asp?2020/69/1/53/282300

  Introduction Top

The nervus terminalis (cranila nerve 0) is a tiny cranial nerve located rostral to the olfactory nerve. Its fibers are independent of those of septal nerve from vomeronasal organ and olfactory nerve from olfactory epithelium.

In lower vertebrates, it is made up of a single large bundle of nerve fibers, while in humans, it is made up of a plexus of nerve bindles lying on the gyrus rectus on the orbital surface of frontal lobe of cerebral hemisphere medial to olfactory bulb. It consists of unmyelinated fibers that arise from minute ganglia lying near the lamina terminalis. Anteriorly, the fibers of nervus terminalis (NT) pass through cribriform plate of ethmoid medial to the filaments of olfactory nerve to enter nasal cavity, where it ends in the nasal mucosa.

  History Top

The NT was first described by a German scientist Fritsch G in 1878[1] in dogfish shark. They also showed it in labeled the drawing of the brain and labeled it as “uverzahliger nerve” [Figure 1]. This term stands for “supernumery nerve.”
Figure 1: Nervus terminalis shown on the ventral aspect of a dogfish brain

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Later, it was described in detail by Pinkus in 1895[2] and was subsequently named as nerve of Pinkus.

Ten years later, Locy[3] described this nerve in detail in selachians and named it as NT.

It was first identified in human fetuses by Larsell in 1950[4] and in adult humans by Brookover and Johnston in 1914.[5],[6]

In 1987, Demski and Schwanzel-Fukuda[7] named this nerve as cranial nerve zero because it was attached rostral to all other (12) cranial nerves. Since there is no numeral for “0” in the Roman numbering system; all the cranial nerves should be renumbered with NT, which has been done long back in the past.[8] In this way, NT will become cranial nerve I. Since the earlier numbering system is so well established that any change in it will not seem prudent to readers, and hence it was numbered as cranial XIII.

Further, there is no symbol for zero in the Roman numbering system, similar to that of Indian and Arabic zero. For this reason, the Vilensky[9] suggested that NT should be named as cranial nerve nulla (Latin word null = none to symbolize).

The NT was a common finding in adult humans Fuller GN and Burger PC, 1990[10] and Fields R.D., 2007[11]

  Structure Top

The NT (“0” pair of cranial nerve) is present bilaterally as minute plexus of unmyelinated peripheral nerve bundles in the subarachnoid space on the orbital surface of the frontal lobe of the cerebral hemisphere lying on the gyrus rectus[11] [Figure 2]. These bundles consist of both unmyelinated autonomic and sensory nerve fibers. According to Pearson, 1941,[12] and Larsell, 1950,[4] the autonomic fibers reach the Bowman's glands and nasal blood vessels.
Figure 2: Bilateral plexus of nerve fascicles of nervus terminalis covering the gyrus rectus of the human brain

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The fibers are NT that arises from minute ganglia lying on cribriform plate of ethmoid near the lamina terminalis. These ganglia give rise to both afferent and efferent fibers.

The fibers of NT pass anteriorly through foramina of cribriform plate, medial to fila of olfactory nerve to enter the nasal cavity, where it runs along the side of nasal septum with olfactory and nasopalatine nerves to supply the Bowman's glands and blood vessels within the nasal mucosa.

Posteriorly, the fibers of NT pass to the region of olfactory trigone, medial olfactory gyrus, and lamina terminalis.[3],[11]

  Embryology Top

From the beginning of the 20th century, numerous studies have been done regarding the origins and stages of olfactory structures in human beings.[12],[13],[14],[15],[16] According to these studies, the fibers of NT are of neural crest origin and migrate from the olfactory placode area to the nasal and cranial brain area.

These fibers of neural crest origin contribute to the gonadotropin-releasing hormone (GnRH)-secreting neurons. Further, the NT plays an important role in GnRH-I neuronal migration independent of olfactory and vomeronasal connections to the olfactory bulbs.[17],[18] The origin of nerve fibers from neural crest cells was confirmed using immunoperoxidase staining for S-100 protein a marker. In 1980, the Schwanzel-Fukuda and Silverman[19] demonstrated immune reactive luteinizing hormone-releasing hormone (LHRH) in neurons in the ganglia of NT, but LHRH-like immunoreactivity was not found in the olfactory and vomernosal nerves. This clearly showed that LHRH (an analog of GnRH) containing neurons of NT belongs to separate system than that of olfactory system.

  Functions Top

In 1983, Demski and Northcutt[20] suggested that in dogfish, the NT is a primary chemosensory pathway for mediating a response to sexual pheromones.

In 1987, Wirsig and Leonard[21] stated that the transaction of NT in male hamsters decreases frequency of mating and increases the number of intromissions for ejaculation.

According to Whitlock,[17] the NT has a neuromodulatory role and modulates the pheromone-mediated sexual behavior. They further supported the view that the neuromodulatory cells of NT arise from neural crest cells. According to Fields, 2007,[10] this nerve is very important with regard to pheromones and sex behavior.

The NT also plays an important role in the development and maturation of hypothalamic–pituitary–gonadal axis.[11],[22]

The NT releases LHRH or GnRH which causes the pituitary gland to secrete luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in female and testosterone in males.[23],[24]

It was also noted that if NT is interrupted, the changes are seen in the development of gonads and sexual behavior of the individual.

  Discussion Top

According to the current standard textbooks of anatomy such as Gray's Anatomy,[25] Gray's Anatomy,[26] Gray's Anatomy for Students,[27] there are only 12 pairs of cranial nerves in human beings, but recently, a new cranial nerve called NT has been discovered by the scientists.

The NT provides a special chemosensory pathway of olfaction and affects the secretion of LH-releasing factor from the hypothalamus. The NT probably also plays an important role in smell (pheromones)-mediated sex behavior.[28] The women's sense of smell is most acute when they are ovulating or when living together.[29] Since caudally, the fibers of NT project to the medial and lateral septal nuclei and preoptic areas. All these areas are known to be involved in regulating sexual behavior in mammals.[10]

Recently, it has been confirmed that an inconspicuous group of neurons called “kisspeptin (KP) neuronal network” is present in the above-mentioned areas.[30],[31]

The “KP neuronal network” induces GnRH secretion from the hypothalamus which in turn regulates the secretion of LH and FSH. These hormones influence the synthesis and release of sex steroids from the gonads. This nerve provides a route through which pheromones are processed, i.e. play an important role in smell-mediated sexual behavior.[32] Further research work is required using newer techniques such as transmission electron microscopy and immunohistochemistry to further unfold the intricacies of its structure and function.

  Clinical Correlation Top

The nerve fibers of NT are extremely thin and hence torn inadvertently while exposing the brain.[14] Therefore, very careful dissection is required during surgery to visualize this nerve. This poses a big challenge to neurosurgeons and ENT surgeons during surgical procedures to avoid the laceration of NT. If NT is damaged during these procedures, it will lead to change in the reproductive behavior of an individual. Further, it may also cause GnRH deficiencies associated with Kallmann syndrome,[30] a clinical condition characterized by delayed puberty and an impaired sense of smell.

  Conclusion Top

The NT is no more an enigmatic cranial nerve. It is present bilaterally in human beings. However, it is often not seen during routine classroom dissection by students, during autopsies by forensic experts, and during surgical procedures by surgeons because it is too thin and hence often torn with dura while exposing the brain.[33] The NT is involved in the release of GnRH from hypothalamus which plays an important role in the development of gonads and probably in smell-mediated sexual behavior of an individual.

Considering the presence and significance of NT in humans, this nerve deserves to be included in the standard textbooks of anatomy, neuroanatomy, and ENT and taught to the medical students.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Fritsch G. Studies on the fieneren construction of the Fish brain with special consideration of homologies in other vertebrate classes. Berlin: Publishing house of the Gutmann'schen bookstore; 1878.  Back to cited text no. 1
Pinkus F. The cranial nerves of the protopterus annectens. Morph Arb 1895;4:275-346.  Back to cited text no. 2
Locy WA. On a newly recognized nerve connected with the forebrain of selachians. Anat Anz 1905;26:33-63.  Back to cited text no. 3
Larsell O. The nervus terminalis. Ann Otol Rhinol Laryngol 1950;59:414-38.  Back to cited text no. 4
Brookover C. The nervus terminalis in adult man. J Comp Neurol 1914:24:131-5.  Back to cited text no. 5
Johnston JB. The nervus terminalis in man and mammals. Anat Rec 1914;8:185-98.  Back to cited text no. 6
Demski LS, Schwanzel-Fukuda M. The terminal nerve (nervus terminalis): Structure, function, and evolution. Introduction. Ann N Y Acad Sci 1987;519:ix-xi.  Back to cited text no. 7
Shaw JP. A history of the enumeration of the cranial nerves by European and British anatomists from the time of Galen to 1895, with comments on nomenclature. Clin Anat 1992:5:466-84.  Back to cited text no. 8
Vilensky JA. The neglected cranial nerve: Nervus terminalis (cranial nerve N). Clin Anat 2014;27:46-53.  Back to cited text no. 9
Fuller GN, Burger PC. Nervus terminalis (cranial nerve zero) in the adult human. Clin Neuropathol 1990;9:279-83.  Back to cited text no. 10
Fields RD. Sex and the secret nerve. Sci Am Mind 2007;18:20-7.  Back to cited text no. 11
Pearson AA. The development of the nervus terminalis in man. J Comp Neurol 1941;75:39-66.  Back to cited text no. 12
Bossy J. Development of olfactory and related structures in staged human embryos. Anat Embryol (Berl) 1980;161:225-36.  Back to cited text no. 13
Wirsig-Wiechmann CR, Wiechmann AF, Eisthen HL. What defines the nervus terminalis? Neurochemical, developmental, and anatomical criteria. Prog Brain Res 2002;141:45-58.  Back to cited text no. 14
Müller F, O'Rahilly R. Olfactory structures in staged human embryos. Cells Tissues Organs 2004;178:93-116.  Back to cited text no. 15
Whitlock KE, Wolf CD, Boyce ML. Gonadotropin-releasing hormone (GnRH) cells arise from cranial neural crest and adenohypophyseal regions of the neural plate in the zebrafish, Danio rerio. Dev Biol 2003;257:140-52.  Back to cited text no. 16
Whitlock KE. Development of the nervus terminalis: Origin and migration. Microsc Res Tech 2004;65:2-12.  Back to cited text no. 17
Taroc EZM, Prasad A, Lin JM, Forni PE. The terminal nerve plays a prominent role in GnRH-1 neuronal migration independent from proper olfactory and vomeronasal connections to the olfactory bulbs. Biol Open 2017;6:1552-68.  Back to cited text no. 18
Schwanzel-Fukuda M, Silverman AJ. The nervus terminalis of the guinea pig: A new luteinizing hormone-releasing hormone (LHRH) neuronal system. J Comp Neurol 1980;191:213-25.  Back to cited text no. 19
Demski LS, Northcutt RG. The terminal nerve: A new chemosensory system in vertebrates? Science 1983;220:435-7.  Back to cited text no. 20
Wirsig CR, Leonard CM. Terminal nerve damage impairs the mating behavior of the male hamster. Brain Res 1987;417:293-303.  Back to cited text no. 21
Wirsig-Wiechmann CR, Wiechmann AF. Vole retina is a target for gonadotropin-releasing hormone. Brain Res 2002;950:210-7.  Back to cited text no. 22
Kiernan JA. Barr's The Human Nervous System: An Anatomical Viewpoint. 9th ed. Baltimore, MD: Lippincott Williams & Wilkins; 2009.  Back to cited text no. 23
Sonne J, Lopez-Ojeda W. Neuroanatomy, Cranial Nerve O (Terminal Nerve). StatPearls: Publishing Treasure Island (FL); 2019.  Back to cited text no. 24
Standring S. Gray's Anatomy: The Anatomical Basis of Clinical Practice. 41st ed. London: Elsevier; 2016.  Back to cited text no. 25
Moore KL, Dalley AF, Agur AMR. Clinically Oriented Anatomy. 5th ed. Lippincott: Williams and Wilkins Baltimore; 2006.  Back to cited text no. 26
Drake RL, Yogi AW, Mitchell AWN. Gray's Anatomy for Students. 2nd ed. Philadelphia: Churchill Livingstone, Elsevier; 2010.  Back to cited text no. 27
Singh V. Textbook of Clinical Anatomy. 3rd ed. India: Elsevier, Relx India; 2016. p. 90.  Back to cited text no. 28
Herz R. The Scent of Desire. New York: Harper Collins; 2007.  Back to cited text no. 29
Mikkelsen JD, Simonneaux V. The neuroanatomy of the kisspeptin system in the mammalian brain. Peptides 2009;30:26-33.  Back to cited text no. 30
Lehman MN, Hileman SM, Goodman RL. Neuroanatomy of the kisspeptin signaling system in mammals: Comparative and developmental aspects. Adv Exp Med Biol 2013;784:27-62.  Back to cited text no. 31
Baum MJ, Bakker J. Roles of sex and gonadal steroids in mammalian pheromonal communication. Front Neuroendocrinol 2013;34:268-84.  Back to cited text no. 32
Bordoni B, Zanier E. Cranial nerves XIII and XIV: Nerves in the shadows. J Multidiscip Healthc 2013;6:87-91.  Back to cited text no. 33


  [Figure 1], [Figure 2]


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