xliv. Rods and cones and the “new” ipRGC

30 July 2009 at 20:16 | Posted in Circadian rhythm | 9 Comments
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We learned in middle school that there are two, and only two, types of light sensitive cells in the retina, rods and cones, right?   Right, that’s what we learned.  Could be the science teachers are still saying that, since the third type was discovered within the last decade. 

Mammalian retina

Mammalian retina

The mammalian retina consists of many layers.  One might think that light would first strike the rods and cones, the photosensitive cells we use for vision.  But our retina is “inside out” compared to the more logical layout found in the octopus and its relatives; light in our eyes must travel through the many retinal layers to reach our rods and cones.  

One of the first layers the light reaches is composed of the one and a half million ganglion cells, most of which are involved in processing visual (image forming) information.  Fewer than 25000, some say just a couple thousand, of these cells are themselves sensitive to light. They function as light meters and they function much more slowly than the rods and cones, not registering abrupt fluctuations in light intensity.  These cells project their axons to several brain centers including the suprachiasmatic nuclei, SCN, the “body clock” through the retinohypothalamic tract.  They thus provide the major clue for the adjustment of the body clock.  The incoming information about light intensity is also used to adjust pupil size (narrowing of pupils in bright light) and to regulate physical activity and melatonin synthesis. 

Newly discovered, they are called by many names:

  • intrinsically photosensitive Retinal Ganglion Cells (ipRGC, also pRGC)
  • photosensitive ganglion cells
  • melanopsin-containing retinal ganglion cells
  • melanopsin-expressing retinal ganglion cells (mRGC)

 Melanopsin jpg

Late in the previous century, scientists weren’t sure that there existed ipRGCs, and those who thought that they do exist were arguing about what opsin, what pigment, they use.  Is it  melanopsin or one of the cryptochromes, which also respond to blue light?  One argument against melanopsin was that it resembles invertebrate opsins and differs from other opsin photopigments found in vertebrates.  

Again, as with our hormone melatonin, it was research on specialized light-sensitive cells of frog skin which provided answers.  

It has been known for a while that even when vision is lost, the light-sensitive ganglion cells may function perfectly.  Recent research on mice at Salk Institute shows that the opposite also is true.  A way was found to knock out the ipRGCs while leaving the rods and cones alone.  The mice became arrhythmic, but still could see. 

One of the researchers speculates:  “It is entirely possible that in many older people a loss of this light sensor is not associated with a loss of vision, but instead may lead to difficulty falling asleep at the right time.”

Update:  I’ve just discovered a wonderful post, Why can’t human eyes detect all wavelengths?, on the blog of Xenophilius Lovegood (!?).  Xeno, claiming to be “a slightly mad scientist”, explains the physical / chemical / electrical changes in the rods and cones as they react to light.  He also has a bit about the ipRGCs.  Recommended.


Next post:  xlv.  Some helpful links


xxx. Light Therapy, Practice Parameters, 1999

23 February 2007 at 11:37 | Posted in Circadian rhythm | Leave a comment
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Practice Parameters for the Use of Light Therapy in the Treatment of Sleep Disorders appeared in SLEEP, Vol. 22, No. 5, 1999. The authors, Chesson et al, were all connected to universities and medical institutions in the USA. 

The clinical guidelines developed by the Standards of Practice Committee were reviewed and approved by the Board of Directors of the American Academy of Sleep Medicine. The guidelines provide recommendations for the practice of sleep medicine in North America regarding the use of light therapy for treatment of various sleep disorders.  

 “These practice parameters define principles of practice that should meet the needs of most patients in most situations.” 

As the PDF apparently no longer is available on the Internet and the document is found only in Google’s html version, I’m offering some excerpts here. I’m leaving out altogether the sections on shift work and other voluntary shifts of sleep-wake schedules, sleep disturbances in the elderly, jet lag and Seasonal Affective Disorder (SAD).  Update, December 2010:  the PDF is now here, hat tip to ttt.

Almost 10 years old, the guidelines can hardly be said to be up-to-date. Much of the information is, however, correct, and it is interesting to see what doctors “should have known” at the turn of the century, at least in the USA. [Emphasis, bold, is mine.] 

From the INTRODUCTION: Endogenous circadian rhythms are in large part regulated by the hypothalamic suprachiasmatic nuclei (SCN). The SCN are key regulators of sleep, as they regulate rhythms that promote sleep and wakening. It is now recognized that a number of sleep disorders are linked to abnormal circadian rhythms or to a lack of coordination of the sleep-wake cycle with the individual’s circadian rhythms. One of the most potent external factors that can alter the period of the SCN is light exposure. 

From BACKGROUND: Over the past two decades, laboratory studies have demonstrated that scheduled light exposure can produce a dose-dependent phase shift in the endogenous circadian rhythms of a variety of variables. These variables include plasma or saliva melatonin, core body temperature, cortisol and a propensity to sleep. 

The rationale for the use of light therapy evolves from the observation that circadian rhythms in humans can be phase-shifted by scheduled exposure to light. Because of an endogenous pattern of light sensitivity, the direction of the phase shift varies with the timing of the light exposure. The responses of circadian rhythms to light exposure have been summarized in Phase Response Curves (PRC).  The PRC appears phase-locked to the core body temperature and plasma melatonin concentration rhythm. In healthy young subjects, with a normal sleep pattern and temperature curve, the core body temperature minimum typically occurs about two hours before habitual wake time (around 4 to 5 a.m.).

  • Light exposure prior to the endogenous minimum of the core body temperature will shift rhythms to a later clock time (i.e., will delay rhythms).
  • Light exposure just after the endogenous circadian body temperature minimum will shift rhythms to an earlier clock time (i.e., will advance rhythms).


Light therapy appears to be a generally safe treatment option for some circadian rhythm disorders…  

Rarely, light therapy may provoke a hypomanic state in patients with bipolar affective disorders.

TREATMENT OBJECTIVES, INDICATIONS and FOLLOW-UP: Treatment is indicated only if there is a desire on the patient’s part to resolve symptoms. The objective is to achieve a sleep onset at either a more socially acceptable time or at a time that provides sufficient sleep in keeping with the work schedule or lifestyle. 

Objective documentation is generally limited to a shift in the core body temperature minimum, a shift in the onset of dim light melatonin secretion or in the peak of the melatonin rhythm, information the patient has recorded in diaries, or actigraphic measurement of rest/activity patterns.

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Next page:


1. Delayed Sleep-Phase Syndrome (DSPS)

2. Advanced Sleep-Phase Syndrome (ASPS)

3. Non-24-Hour Sleep-Wake Syndrome (NON-24)


Next:  xxxi. Light Therapy Recommendations, 1999


ix. Melatonin and the effect of light

26 November 2005 at 16:49 | Posted in Circadian rhythm | Leave a comment
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Oops, sorry.  Got a little ahead of myself there.  Melatonin should have been explained before that more technical stuff.
Melatonin is a hormone produced and secreted by the pineal, a tiny, midbrain gland which doesn’t seem to have any other tasks.
The pineal takes its orders from a nearby organ which Mary Poppins surely should have sung about, the suprachiasmatic nuclei.  However you choose to pronounce that, it’s a whole dance tune in itself.  The SCN (for short) is our central biological clock.  If totally isolated from outside cues about time, it will keep running on its own “almost a day” (= circadian) cycles virtually indefinitely.  Cells from mammalian SCN do so, in fact, in a dish.  
The body clock needs to be reset daily.  The SCN receives (or receive, if you prefer) information from the retina directly along a pathway called the retino-hypothalamic tract.  And yes, the SCN is located in the hypothalamus, in the brain. 
The vital information which the SCN processes, is sent to it by special light-sensitive cells in the retina in the back of the eye.  This information about light received at the retina has nothing to do with vision.  It tells our system when day and night are.  There can be other cues as well, such as mealtimes and activities, but light is by far the strongest.  
The rhythms of core body temperature (CBT) and melatonin secretion, at the least, need to be coordinated with each other and with the cycle of light/dark to allow us to fill our need for one long sleep-session, preferably at night.  
The level of melatonin in the blood during the (subjective) day is (or should be) near zero.  As CBT falls during an individual’s night, then starts rising again about two hours before wake-up time, our melatonin level rises during the first half of the night, to drop off during the second.  However, the two curves are not mirror images of one another.  The melatonin level rises quite sharply and then stays on a plateau.  It starts falling a couple of hours before the CBT bottoms out.  Here’s how this is shown in post no. xiii:  


Bright light banishes melatonin from the blood and stops / delays the secretion of it.  

A person with a normal circadian system who cooperates with nature’s signals will sleep at the same time every night.  The schedule might look like this:

  • 8 or 9 p.m., melatonin secretion starts, perhaps not measurable yet (DLMO, Dim Light Melatonin Onset)
  • 10 p.m., calming down, lights are dim
  • 10:30, feet are hot, person feels sleepy
  • 11 p.m., asleep
  • 3 a.m., melatonin level starts receding
  • 5 a.m., core body temperature minimum
  • 7 a.m., wake up, and light exposure banishes the remainder of the melatonin 

We all know people who’d rather sleep 10 p.m. to 6 a.m. or midnight to 8 a.m.  Those schedules are within the normal range.  

When I was a kid, medicine and science thought that the normal range should be achievable for everyone.  It is not.


Next:  x. Other animals


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