neuroanatomy Neuroanatomy is the study of the structure and organization of the nervous system. In contrast to animals with radial symmetry, whose nervous system consists of a distributed network of cells, animals with bilateral symmetry have segregated, defin ...

, the retinohypothalamic tract (RHT) is a photic neural input pathway involved in the

circadian rhythms A circadian rhythm (), or circadian cycle, is a natural, internal process that regulates the sleep–wake cycle and repeats roughly every 24 hours. It can refer to any process that originates within an organism (i.e., endogenous) and responds to ...

mammal Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or ...

s. The origin of the retinohypothalamic tract is the

intrinsically photosensitive retinal ganglion cells Intrinsically photosensitive retinal ganglion cells (ipRGCs), also called photosensitive retinal ganglion cells (pRGC), or melanopsin-containing retinal ganglion cells (mRGCs), are a type of neuron in the retina of the mammalian eye. The presence ...

(ipRGC), which contain the photopigment melanopsin. The

axon An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action po ...

s of the ipRGCs belonging to the retinohypothalamic tract project directly, monosynaptically, to the

suprachiasmatic nuclei The suprachiasmatic nucleus or nuclei (SCN) is a tiny region of the brain in the hypothalamus, situated directly above the optic chiasm. It is responsible for controlling circadian rhythms. The neuronal and hormonal activities it generates regula ...

(SCN) via the

optic nerve In neuroanatomy, the optic nerve, also known as the second cranial nerve, cranial nerve II, or simply CN II, is a paired cranial nerve that transmits visual information from the retina to the brain. In humans, the optic nerve is derived fro ...

and the

optic chiasm In neuroanatomy, the optic chiasm, or optic chiasma (; , ), is the part of the brain where the optic nerves cross. It is located at the bottom of the brain immediately inferior to the hypothalamus. The optic chiasm is found in all vertebrat ...

. The suprachiasmatic nuclei receive and interpret information on environmental light, dark and day length, important in the

entrainment Entrainment may refer to: * Air entrainment, the intentional creation of tiny air bubbles in concrete * Brainwave entrainment, the practice of entraining one's brainwaves to a desired frequency * Entrainment (biomusicology), the synchronization o ...

of the "body clock". They can coordinate peripheral "clocks" and direct the

pineal gland The pineal gland, conarium, or epiphysis cerebri, is a small endocrine gland in the brain of most vertebrates. The pineal gland produces melatonin, a serotonin-derived hormone which modulates sleep, sleep patterns in both circadian rhythm, circ ...

to secrete the hormone melatonin.

Structure

The retinohypothalamic tract consists of

retinal ganglion cells A retinal ganglion cell (RGC) is a type of neuron located near the inner surface (the ganglion cell layer) of the retina of the eye. It receives visual information from photoreceptors via two intermediate neuron types: bipolar cells and retina ...

.http://www.ifc.unam.mx/curso_ritmos/capitulo12/Hannibal021.pdf A distinct population of ganglion cells, known as

(ipRGCs), is critically responsible for providing non-image-forming visual signals to the brain. Only about two percent of all retinal ganglion cells are ipRGCs, whose cell bodies are in mainly the ganglion cell layer (and some are displaced in the inner nuclear layer of the retina). The photopigment melanopsin is present on the dendrites of ipRGCs, giving ipRGCs sensitivity to light in the absence of rod or cone input. The dendrites spread outwards from ipRGCs within the inner plexiform layer. These dendrites can also receive more canonical signals from the rest of the neuroretina. These signals are then carried through the

, which projects to the

suprachiasmatic nucleus The suprachiasmatic nucleus or nuclei (SCN) is a tiny region of the brain in the hypothalamus, situated directly above the optic chiasm. It is responsible for controlling circadian rhythms. The neuronal and hormonal activities it generates regula ...

(SCN), anterior hypothalamic area, retrochiasmatic area, and lateral hypothalamus. However, a major portion of the RHT ends in the SCN.

Neurotransmitters

Glutamate

Glutamate Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can syn ...

levels in the RHT are measured by means of immunoreactivity. Retinal nerve terminals display a significantly higher content of glutamate immunoreactivity than the postsynaptic dendrites and non-retinal terminals. The higher immunoreactivity in terminals shows that is readily available before transmission and is used up as the electrical signals travel along the RHT. The synapse of glutamate to the SCN has been shown to cause

phase shift In physics and mathematics, the phase of a periodic function F of some real variable t (such as time) is an angle-like quantity representing the fraction of the cycle covered up to t. It is denoted \phi(t) and expressed in such a scale that it ...

s in circadian rhythms, discussed more in detail later.

Pituitary adenylate cyclase-activating polypeptide (PACAP)

Pituitary adenylate cyclase-activating polypeptide Pituitary adenylate cyclase-activating polypeptide also known as PACAP is a protein that in humans is encoded by the ''ADCYAP1'' gene. pituitary adenylate cyclase-activating polypeptide is similar to vasoactive intestinal peptide. One of its effec ...

(PACAP) is co-stored and co-transmitted with glutamate in retinal terminals. More than ninety percent of all RHT projecting fibers to the SCN store PACAP. White light induces activation of ganglion cells containing PACAP. This allows for the concentration in SCN to be lower during the day and higher at night because humans are exposed to light more during the day and are having greater optic nerve stimulation.

Effect on circadian rhythms

The SCN of the hypothalamus contains an endogenous pacemaker that regulates circadian rhythms. The

zeitgeber A zeitgeber () is any external or environmental cue that entrains or synchronizes an organism's biological rhythms, usually naturally occurring and serving to entrain to the Earth's 24-hour light/dark and 12-month cycles. History The term ' (; ) ...

found to have the most profound effect on the SCN is light, which is the form of stimulation of which conversion is needed for it to be processed by the brain. Neurotransmitters that travel the RHT are responsible for delivering this message to other parts of the brain. If damage is done to this important pathway, alterations in circadian rhythms including phase shifts may occur. Studies done on rats show that even with severely degenerated photoreceptors (blind, no visible light perception), they have the ability to entrain to the light/dark cycle because they have intact RHTs. A study was conducted to observe the differences in three groups of Sprague-Dawley rats: ones that had part of the RHT pathway cut when it was an adult (AE), ones that had part of the pathway cut within 24 hours of their birth (NE), and a control group.Stephan, F. K. (1978). Developmental plasticity in retinohypothalamic connections and the entrainment of circadian rhythms. Further development of the brains of those in the NE group showed that the two suprachaismatic nuclei (SCN) have nearly equal inputs shortly after the pathway is cut. This was shown to drastically slow down the re-synchronization of internal biological rhythms to the external time cues, primarily light. Rats in the AE and NE groups similarly reduced the amount of fluid intake during the study during the hours they were exposed to constant light. This may indicate that the intake of water is affected by the number of connections in this pathway and affect the further development of other parts of the brain that are dependent on light.

Notes

References

{{Authority control Eye Sleep physiology Circadian rhythm Hypothalamus