Does Anybody Really Know What Time It Is? Lamprey Do! by Don Orth

We humans are obsessed about time. Our lives are structured around time.  We take time management workshops with a false belief that we can manage time.  Yet, we can only manage to prioritize activities, not time. My alarm rings at 6:00am, I fail to notice a sunrise at 6:29am, eat, shower, start my commute (clock in my car reads 7:34am), arrive to many auto-scheduled emails, approve time sheets, grade assignments, impose late submission penalties, attend committee meeting at 10:00am, arrive to class at 12:20pm, dismiss class promptly at 1:10pm, and the whole day is scheduled like that. The sun sets at 8:06pm and I might ponder the peculiar nature of time in our modern world.  Our obsession with time has a very long evolutionary history that is evident in all animals.

The lyrics from The Chicago Transit Authority’s hit song, “Does Anybody Really Know What Time It Is?” (1969), questions this obsession with time

“As I was walking down the street one day
A man came up to me and asked me what the time was that was
On my watch, yeah
And I said
Does anybody really know what time it is
I don't
Does anybody really care
If so I can't imagine why
About time
We've all got time enough to cry”

The song is about caring, the human condition, and human emotions.  The song was written at a time when many soldiers were dying in Viet Nam and yet the rich and privileged appeared to be unconcerned.   Listen here.  Humans care too much about time,  and not enough about things that matter.  Fish, on the other hand, live their lives with an internal clock that controls timing of biological processes.   

           

Deep within our brain sits a very small endocrine gland called the pineal gland.  It's the size of a pea, and this tiny pineal gland  secretes the melatonin.  Melatonin is a hormone that helps regulate human sleep and wake cycles.  When light hits the retina, a message is sent to your hypothalamus, and nerve fibers transmit this message down the spinal cord to sympathetic nerve cells that then ascend back up to the pineal gland.  Message is received and melatonin secretion ceases.   It’s time to wake up!

In the fishes, a very similar mechanism is at work to allow a fish to track changes in day length and time development and maturation of the gonads. Fish, like other animals, secrete melatonin at night and exhibit circadian rhythms.  Melatonin levels regulate activity of fishes.  Nocturnal fishes became active when melatonin levels increase, whereas diurnal fishes become active when melatonin levels are low.  Fish do not sleep in the same way humans do.  For one thing, they have no eyelids so the eye remains open.  Metabolism and behaviors slow, but they don’t appear to have deep sleep REM cycles (Laming 1981).

Hagfishes and the lampreys, the most primitive fishes, have the capacity to detect light and dark.  Hagfish have no eyes and no pineal gland, but do possess primitive photoreceptors that have nerve connections to brain.  The lamprey eye develops slowly during larval stage, but is functional early in life.  Lampreys also have a pineal gland at the top of head above brain.  The tissue overlying the pineal gland is transparent in the larval stage and translucent in the adult.  It appears the photosensitive pineal functions in an analogous manner as the retina photoreceptors in the human. The molecular mechanisms are the subject of ongoing studies of evolution of vertebrate photoreceptors (Mano and Fukada 2007) and the pervasive influence of circadian rhythms.  The blind Mexican tetra has been cut off from cues of the rising and setting sun; it has no circadian rhythms. 

Parapinopsin (A) and rhodopsin (B) pigments are expressed in different regions of photoreceptor cells   Photo from Koyanagi et al. (2004).  P=pineal, PP=parapineal, L=lumen, and S=pineal stalk.  (Scale bar=100 μm) Source

In the lamprey, the pineal gland has two components, a pineal (upper gland in photo) and a parapineal (lower gland in photo).  Each has two parts with UV and visible light sensitive regions. Research on the lamprey pineal gland confirmed that visible light excites the pineal, while UV light inhibits the pineal response (Koyanagi et al. 2004).  Therefore, the lamprey really do know what time it is!  

Zebrafish is a valuable vertebrate model due to fast development, short generation time, and a large number of embryos.  Consequently, they are frequent subjects for the study of the circadian clock and the pineal gland.  The pineal gland develops early in the zebrafish, is photoreceptive and contains an intrinsic circadian oscillator that controls many physiological and behavioral processes.   

Location of pineal gland in zebrafish (top) and zebrafish embryo. Photos by Yoav Gothilf

Zebrafish have a gene, aanate (or for a long version, that would be aralkylamine-N-acetyltransferase), that exhibits clock-controlled rhythms (Gothilf et al. 1999).  Imagine a gene that is light sensitive; light is mandatory to set the circadian clock in zebrafish.  The gene exists in every cell allowing for the study of this “clock gene” in zebrafish cell lines (Vallone et al. 2005). The clock gene has a circadian rhythm in gene expression, which translates to circadian rhythms in metabolism and behavior in the zebrafish. 

What does this mean to the practicing fish worker?  Circadian rhythms in fish are established by the prevailing day/night cycles.  Maintenance of the circadian rhythms is important to the well-being of fish.  It is possible to control photo and thermal cycles and reduce the time needed for reproductive maturation in captive, farmed fish (Blythe et al. 1994). Alternatively, hormone injections may advance gonadal development.  Light and dark cycles and feeding times can also be controlled to optimize growth and survival of fish in captivity.  Fish are also great subjects for school science projects.  Novice scientists can observe the daily activity patterns of fish in an aquarium and experiment with changing time of day when lights are turned on.  They study fish!  They become more curious! They begin to contemplate life!  They begin to really know what matters!

References

Blythe, W.G., L.A. Helfrich, and G. Libey. 1994. Induced maturation of striped bass (Morone saxatilis) exposed to 6-, 9-, and 12-month photothermal regimes.  Journal of the World Aquaculture Society 25:183-192.

Gothilf, Y, et al. 1999. Zebrafish serotonin N-acetyltransferase-2: marker for development of pineal photoreceptors and circadian clock function. Endocrinology 140:4895-4903.  

Koyanagi, M., et al.  2004. Bistable UV pigment in the lamprey pineal. Proceedings of the National Academy of Sciences 101:6687-669. 

Laming, P.R. 1981.  Brain mechanisms of behaviour in lower vertebrates.  (Society for Experimental Biology Seminar Series).  Cambridge University Press, Oxford.  332 pp.

Mano, H., and Y. Fukada. 2007.  A median third eye: pineal gland retraces evolution of vertebrate photoreceptive organs.  Photochemistry and Photobiology 83(1):11-18.  DOI: 10.1562/2006-02-24-IR-813.  

Noche, R.R., P.N. Lu, L. Goldstein-Kral, E. Glasgow, and J.O. Liang. 2011. Circadian rhythms in the pineal organ persist in zebrafish larvae that lack ventral brain. BMC Neurosciences 12:7. DOI:10.1186/1471-2202-12-7.    

Vallone, D., K. Lahiri, T. Dickmeis, and N.S. Foulkes. 2005.  Zebrafish cell clocks feel the heat and see the light! Zebrafish 2(3):171-187. DOI: 10.1089/zeb.2005.2.171