Clock Tutorials

This is an appropriate time of year for this post (February 05, 2006)... ----------------------------------------------------- So, why do I say that it is not surprising the exposure to bright light alleviates both seasonal depression and other kinds of depression, and that different mechanisms may be involved? In mammals, apart from visual photoreception (that is, image formation), there is also non-visual photoreception. The receptors of the former are the rods and cones that you all learned about in middle school. The receptors for the latter are a couple of thousand Retinal Ganglion…
This post was originally written on February 11, 2005. Moving from relatively simple mammalian model to more complex systems. I have previously described the basic properties of the circadian organization in mammals. Non-mammalian vertebrates (fish, amphibians, reptiles and birds) have more complex circadian systems than mammals. While the suprachiasmatic area remains a site of circadian pacemakers, it is, unlike in mammals, not the only such site. The pineal organ, which in mammals is a purely secretory organ, is directly photosensitive in other vertebrates (with the exception of snakes)…
When teaching human or animal physiology, it is very easy to come up with examples of ubiqutous negative feedback loops. On the other hand, there are very few physiological processes that can serve as examples of positive feedback. These include opening of the ion channels during the action potential, the blood clotting cascade, emptying of the urinary bladder, copulation, breastfeeding and childbirth. The last two (and perhaps the last three!) involve the hormone oxytocin. The childbirth, at least in humans, is a canonical example and the standard story goes roughly like this: When the…
This February 06, 2005 post describes the basic elements of the circadian system in mammals. The principal mammalian circadian pacemaker is located in the suprachiasmatic nuclei (SCN) of the hypothalamus. The general area was first discovered in 1948 by Curt Richter who systematically lesioned a number of endocrine glands and brain areas in rats. The only time he saw an effect on circadian rhythms was when he lesioned a frontal part of hypothalamus (which is at the base of the brain) immediatelly above the optic chiasm (the spot where two optic nerves cross). Later studies in the 1970s…
If you really read this blog 'for the articles', you know some of my recurrent themes, e.g., that almost every biological function exhibits cycles and that almost every cell in every organism contains a more-or-less functioning clock. Here is a new paper that combines both of those themes very nicely, but I'll start with a little bit of background first. Daily Rhythms in Sensory Sensitivity If almost every biochemical, physiological and behavioral function exhibits daily cycles, it is no surprise that such rhythms have been discovered in sensory sensitivity of many sensory modalities -…
This post from February 03, 2005 covers the basic concepts and terms on entrainment. This is also the only blog post to date that I am aware of that was cited in a scientific paper. Let's now continue our series of Clock Tutorials with an introduction to some phenomena (and related terms and concepts) observed in the laboratory in the course of doing standard circadian experiments. Such experiments usually involve either the study of properties of freerunning rhythms (check the old tutorials, especially CT2 and CT 4 for clarification of basic terms and concepts), or the analysis of…
You probably realize by now that my expertise is in clocks and calendars of birds, but blogging audience forces me to occasionally look into human clocks from a medical perspective. Reprinted below the fold are three old Circadiana posts about the connection between circadian clocks and the bipolar disorder, the third one being the longest and most involved. Here are the links to the original posts if you want to check the comments (especially the first comment on the third post): January 18, 2005: Clocks and Bipolar Disorder August 16, 2005: Bipolar? Avoid night shift February 19, 2006:…
I wrote this post back on February 02, 2005 in order to drive home the point that the circadian clock is not a single organ, but an organ system comprised of all cells in the body linked in a hierarchical manner: In the earliest days of chronobiology, the notion of circadian organization was quite simple. Somewhere inside the organism there was a clock. It was entrained by light via photoreceptors (e.g., the eye) and it drove the rhythms of various biochemical, physiological and behavioral events in the body: Very soon this simple notion became difficult to sustain in light of new data. For…
As we mentioned just the other day, studying animal behavior is tough as "animals do whatever they darned please". Thus, making sure that everything is controlled for in an experimental setup is of paramount importance. Furthermore, for the studies to be replicable in other labs, it is always a good idea for experimental setups to be standardized. Even that is often not enough. I do not have access to Science but you may all recall a paper from several years ago in which two labs tried to simultaneously perform exactly the same experiment in mice, using all the standard equipment, exactly…
I wrote this post back on January 23, 2005. It explains how clock biologists think and how they design their experiments: So, are you ready to do chronobiological research? If so, here are some of the tips - the thought process that goes into starting one's research in chronobiology. First, you need to pick a question. Are you interested in doing science out of sheer curiosity to discover stuff that nobody knew before (a very noble, but hard-to-fund pursuit)? Or would you prefer your work to be applicable to human medicine or health policy, veterinary medicine, conservation biology, or…
Two interesting papers came out last week [from the Archives - click on the clock logo to see the original post], both using transgenic mice to ask important questions about circadian organization in mammals. Interestingly, in both cases the gene inserted into the mouse was a human gene, though the method was different and the question was different: Turning a Mouse Into A Lark The first paper (Y. Xu, K.L. Toh, C.R. Jones, J.-Y. Shin, Y.-H. Fu, and L.J. PtáÄekModeling of a Human Circadian Mutation Yields Insights into Clock Regulation by PER2. Cell, Vol 128, 59-70, 12 January 2007) is…
This post is a modification from two papers written for two different classes in History of Science, back in 1995 and 1998. It is a part of a four-post series on Darwin and clocks. I first posted it here on December 02, 2004 and then again here on January 06, 2005: II. Darwin on Time There is a season for everything And a time for every purpose under the heaven: A time to be born, and a time to die: A time to plant and a time to reap.... (Ecclesiastes) In this section I will attempt to evaluate from Darwin's writings what he thought about the selective role of environmental periodicities…
This is going to be a challenging post to write for several reasons. How do I explain that a paper that does not show too much new stuff is actually a seminal paper? How do I condense a 12-page Cell paper describing a gazillion experiments without spending too much time on details of each experiment (as much as I'd love to do exactly that)? How do I review it calmly and critically without gushing all over it and waxing poetically about its authors? How do I put it in proper theoretical and historical perspective without unnecessarily insulting someone? I'll give it a try and we'll see…
This post about the origin, evolution and adaptive fucntion of biological clocks originated as a paper for a class, in 1999 I believe. I reprinted it here in December 2004, as a third part of a four-part post. Later, I reposted it here. III. Whence Clocks? Origin, Evolution, and Adaptive Function of Biological ClocksThe old saw about the early bird just goes to show that the worm should have stayed in bed. (Heinlein 1973)Now darkness falls. Quail chirps. What use Hawk eyes? (Basho) Local/temporary and global/universal environments. In the study of adaptive functions, usually the question is…
Microarrays have been used in the study of circadian expression of mammalian genes since 2002 and the consensus was built from those studies that approximately 15% of all the genes expressed in a cell are expressed in a circadian manner. I always felt it was more, much more. I am no molecular biologist, but I have run a few gels in my life. The biggest problem was to find a control gene - one that does not cycle - to make the comparisons to. Actin, which is often used in such studies as control, cycled in our samples. In the end, we settled on one of the subunits of the ribosome as we…
This post, originally published on January 16, 2005, was modified from one of my written prelims questions from early 2000. EVOLUTIONARY PHYSIOLOGY OF BIOLOGICAL CLOCKS "Circadian clocks allow organisms to predict, instead of merely react to, cyclic (predictable) changes in the environment". A sentence similar to this one is the opening phrase of many a paper in the field of chronobiology. Besides becoming a truth by virtue of frequent repetition, such a statement appeals to common sense. It is difficult to imagine a universe in which it was not true. Yet, the data supporting the above…
This is a repost of a May 29, 2008 post: I was wondering what to do about the Classic Papers Chellenge. The deadline is May 31st, and I am so busy (not to mention visiting my dentist twice week which incapacitates me for the day, pretty much), so I decided to go back to the very beginning because I already wrote about it before and could just cannibalize my old posts: this one about the history of chronobiology with an emphasis on Darwin's work, and this one about Linnaeus' floral clock and the science that came before and immediately after it. In the old days, when people communed with…
This is the third in the series of posts designed to provide the basics of the field of Chronobiology. This post is interesting due to its analysis of history and sociology of the discipline, as well as a look at the changing nature of science. You can check out the rest of Clock Tutorials here. It appears that every scientific discipline has its own defining moment, an event that is touted later as the moment of "birth" of the field. This can be a publication of a paper (think of Watson and Crick) or a book ("Origin of Species" anyone?). In the case of Chronobiology, it was the 1960…
Chad wrote a neat history of (or should we say 'evolution of') clocks, as in "timekeeping instruments". He points out the biological clocks are "...sort of messy application, from the standpoint of physics..." and he is right - for us biologists, messier the better. We wallow in mess, cherish ambiguity and relish in complexity. Anyway, he is talking about real clocks - things made by people to keep time. And he starts with a simple definition of what a clock is: In order to really discuss the physics of timekeeping, you need to strip the idea of a clock down to the absolute bare…
This is the second in the series of posts designed to provide the basics of the field of Chronobiology. See the first part: ClockTutorial #1 - What Is Chronobiology and check out the rest of them here - they will all, over time, get moved to this blog. Here is a brief overview of the concepts and terms used in the field of chronobiology. I will write much more detailed accounts of various aspects of it in the future. Seasons of the year, phases of the moon, high and low tides, and alternation between night and day are examples of cyclic changes in the environment. Each presents a different…