The retinohypothalamic tract (RHT) is a photic neural input pathway involved in the circadian rhythms of mammals. The origin of the retinohypothalamic tract is the intrinsically photosensitive retinal ganglion cells (ipRGC), which contain the photopigment melanopsin. The axons of the ipRGCs belonging to the retinohypothalamic tract project directly, monosynaptically, to the suprachiasmatic nuclei (SCN) via the optic nerve and the optic chiasm. The suprachiasmatic nuclei receive and interpret information on environmental light, dark and day length, important in the entrainment of the "body clock". They can coordinate peripheral "clocks" and direct the pineal gland to secrete the hormone melatonin.
Structure of the RHT
The retinohypolthalamic tract consists of retinal ganglion cells. A source of light emits waves of light that reach the rods and cones of the retina, therefore showing this pathway originates in a distinct population of ganglion cells, known as intrinsically photosensitive retinal ganglion cells (ipRGCs). Only about two percent of all retinal ganglion cells are ipRGCs, which are mostly found on the inner nuclear layer of the retina. However, the dendrites expanding from the cell bodies of these cells form a sensitive covering of the entire retina. These signals are then carried through the optic nerve. It then projects to the suprachiasmatic nucleus (SCN), anterior hypothalamic area, retrochiasmatic area, & lateral hypothalamus. However, a major portion of the RHT ends in the SCN.
Neurotransmitters of the RHT
Glutamate 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 immunoreacticity 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 shifts in circadian rhythms, discussed more in detail later.
Pituitary adenylate cyclase-activating polypeptide (PACAP)
Pituitary adenylate cyclase-activating polypeptide (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 found to have the most profound effect on is light, which is the form of stimulation of which conversion is needed for it to be processed by the brain. The different 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 are susceptible to occur. Studies have been done on rats, showing that even with severely degenerated photoreceptors (visually blind), they have the ability to entrain the light/dark cycle because they have an intact RHT.
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. 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 the internal biological rhythms of the rats to the external time cues, such as 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.
- Gooley JJ, Lu J, Chou TC, Scammell TE, Saper CB (2001). "Melanopsin in cells of origin of the retinohypothalamic tract". Nat. Neurosci. 4 (12): 1165. doi:10.1038/nn768. PMID 11713469.
- from the retina to the optic chiasm, the ipRGC axons follow the same path as the axons of "regular" RGCs (i.e. RGCs that are not intrinsically photosensitive)
- Afifi, A.K.; Bergman, R.A. (2005-01-28). Functional Neuroanatomy (PAPERBACK) (2nd ed.). McGraw-Hill. p. 271. doi:10.1036/0071408126. ISBN 978-0-07-140812-7.
- Irwin, R. (2007). Calcium response to retinohypothalamic tract synaptic transmission in suprachiasmatic nucleus neurons.,
- , Hannibal (2002).
- Stephan, F. K. (1978). Developmental plasticity in retinohypothalamic connections and the entrainment of circadian rhythms.