12 hours ago

My dad is rescuing a pair of boer goats.

I’m really jealous.

Dear Darya,

I googled “question mark candle”, expecting to see a large wax icon to be burned ceremoniously whenever the incinerator needs a time and place to ponder. What a great ritual! This is a birthday cake candle and I am disappointed.

Twin Peaks Marathon.

with Beth, Jax, embroidery, summer syllabus, and free books.

About a billion non-linear notes on the SCN, clocks, and rhythmmmms

 Curtis Richter carried out some of the earliest studies on rhythmic behavior. There are claims that this is the beginning of animal chronobiology. As a grad student in the 1920’s, he worked in the lab of John Broadus Watson at John Hopkins University. Watson had given Richter 12 rats to study. Having never worked with rats, Richter began by observing them without outside stimuli. He covered the windows, soundproofed the lab, separated the rats into individual cages, and began taking measurements. He recorded everything he could monitor about the rats’ activities-movement, food and water intake, defecation, etc.

After earning his doctorate, Richter was hired by John Hopkins and took over for Watson, after he was fired for having an affair with one of his lab assistants. In Richter’s early work, he described rhythmic behavior and invented the running wheel as part of a study on rat activity.

 

British physician, William Ogle, wrote this in 1866 on the diurnal change in the body temperature of humans

 

          There is a rise in the early mornings while we are still asleep, and a fall in the evening while we are still awake, which cannot be explained by reference to any of the hitherto mentioned influences. They are not due to variations in light; they are probably produced by periodic variations in the activity of the organic functions.

Homeostatic motivations determine behavior. As calorie reserves lower, an animal must eat or drink to replenish itself. A rat does things as a learned evolutionary strategy that leads to success. It lives a certain way because it has adapted to living in a predictable environment controlled by its behavior. Richter introduced the notion that the clock may have an even greater role in determining when an animal does what it does.

The next step was to find the clock. Richter conducted a series of experiments including removing the adrenals, gonads, pituitary, thyroid, pineal, and pancreas of rats, using electroshock therapy, inducing convulsions, anaesthetizing, and even getting them drunk. After all of this, they still showed signs of rhythmic behavior. Then he moved to the brain. Richter conducted over 200 studies that damaged various parts of the rats’ brains. In 967, he found that when he damaged the front part of the hypothalamus, he could produce arrhythmic rats.

In humans, the hypothalamus is about the size of an almond. It regulates blood pressure, body temperature, fluid and electrolyte balance, metabolism, and sugar levels. The thalamus and the hypothalamus work together to create the sleep/wake cycle. The hypothalamus also controls the timing of the oestrous cycle in mammals.

The suprachiasmatic nuclei (SCN) is a small paired cluster of cells in the hypothalamus. By removing the SCN, Frederic Stephan, a student of Irving Zucker at Berkeley, was able to abolish the oestrous cycle, drinking, and locomotive behavior. Robert Moore of the University of Pittsburgh was performing experiments on entrainment-advancing or retarding the clock. Moore injected radioactive amino acids into the eyes of rats to follow a light beam as it entered the eye. It was known that exposure to light had something to do with the clock. The radioactive amino acids traveled through the optic nerve, and into the SCN. This pathway was named the retinohypothalamic tract.

When Moore lesioned the SCN, he also disrupted the circadian rhythm. Moore and Zucker found that removing the entire SCN, about 20,000 cells, destroyed both behavioral and endocrine circadian rhythms. It is believed by Buddhists that concentrating on the third eye is the key to enlightenment. The SCN is located directly behind the third eye.

            The problem now was to determine whether the SCN was the clock or merely a link to the clock. It took almost twenty years to find that the SCN was the clock, that it regulated bodily functions, and that it did it within a 24-hour time period.  In the late 1970’s, Shin-Ichi Inouye and Hiroshi Kawamura, of the Institute of Life Science in Tokyo, showed that the SCN generated a 24-hour rhythm of electrical activity. A small electrode was inserted into the brains of rats that measured the electricity of several neurons at once. Inouye and Kawamura recorded the measurement from neurons inside the SCN and compared them to neurons close to, but still outside of the SCN.

            They discovered that cells within the SCN had high levels of electrical activity during the day, and low levels at night. The cells outside the SCN showed the opposite. They then isolated the SCN by severing its connections to the rest of the brain. The rhythm within the SCN continued, but was obliterated in the neurons outside. This meant that the SCN produced its own rhythm, and it provided timing to the rest of the brain via the efferent neurons.

            To dismiss one of the main arguments against the SCN as the clock, Inouye and Kawamura needed to completely remove the SCN from an animal to make sure that all of the neural connections were severed. Luckily, brain tissue lasts about six minutes after removal and they were able to measure the electrical charge it produced. The resulting data showed that the SCN generates a diurnal rhythm and that it was a self-sufficient timekeeper.

            Around 1980, Bill Schwartz, at the University of Massachusetts, had been studying the metabolic function of the SCN. Working tissues consume energy, but the brain is heterogeneous, and needs a continuous supply of glucose to function. 2-geoxyglucose (2DG) is carried to the brain like glucose, but cannot be metabolized to provide energy. Schwartz injected 2DG into a rat’s vein. 45 minutes later, the rats were killed, thinly sliced, and then placed on X-ray films. During a 12 hours light/12 hours dark cycle, Schwartz found that the SCN was metabolically active during the light stage, and mostly inactive during the dark. The SCN was the only part of the brain to exhibit such a strong rhythm. During the mid 1980’s, several labs found that if they transplanted fetal SCN into the brains of SCN-lesioned adult rats, the circadian activity would be restored. Skeptics said that there could have cells separate from the SCN that were accidentally transplanted or that the act of transplanting a new SCN could have been a stimulating factor that activated the dormant host.

            Golden hamsters can be found in labs all around the world, all derived from one breeding pair. Using an inbred strain of hamster means that variations can be reduced. Having variables from animal to animal is a huge problem for experimental biologists. Even with inbred hamsters, at any given time, two hamsters will never have the same heartbeat. The same is true with body temperature, blood pressure, and other vital stats. It has been argued that the time of day should be included whenever recording biological data because our bodies have different norms for different times of the day.

            The percentage of variation in a population is known as a Gaussian distribution or a bell-shaped curve. Variation is caused by environmental or genetic factors. The interaction between environmental and genetic factors, especially during development, results in the formation of the individual. The circadian rhythms of individuals of the same specials, with identical genetics, will differ.

Guassian distribution ex.

        While working on his doctorate in Mike Menaker’s lab, at the University of Oregon, Martin Ralph was monitoring a new group of golden hamsters on running wheels (invented by Curtis Richter). Golden hamsters typically have circadian rhythms of about 24.1 hours when kept in constant darkness.  In the golden hamster population, a few hamsters have had abnormal rhythms, but still in a range from 23- 24.5 hours. Ralph noticed that one of his new hamsters had an unheard of rhythm of 22 hours. This hamster was named the tau mutation. It could provide a clear answer as to whether or not the SCN was the oscillator. If the tau SCN was transplanted into a normal hamster, would that hamster have the donor or recipient’s rhythm?

        Ralph got to work breeding more tau hamsters because transplants work best when using fetal tissue. By selecting two tau hamsters as parents, he ended up with hamsters whose mean rhythm was about 20.2 hours. Ralph and Menaker, and colleagues Russel Foster and Fred Davis, transplanted the tau SCN into arrhythmic hamsters who’s SCN had been destroyed. Every hamster that had received a tau SCN had a rhythm of about 20.2 hours. The hypothesis that the SCN controlled timing was correct.

        Soon thereafter, researchers found that individual SCN cells demonstrated a circadian rhythm. The SCN is composed of cells that oscillate individually, and that time themselves to fire over the course of a 24-hour period.

        To recap, researchers had discovered that light enters the eye, travels through the retinohypothalamic tract to the SCN, where the SCN controls the body’s rhythms. The new question is how the SCN controls bodily functions and communicates. From all of the experiments done on the SCN, researchers have noticed a large amount of neural projections-mostly leading to the hypothalamus, thalamus, and midbrain. Output pathways to the pineal gland show the flow of corticosterone. Corticosterone is a metabolic hormone in most animals. SCN transplantations show that there had to be another form of communication from the SCN, other than neural connections. There have never been any cases of entrainment by light in transplanted SCNs. After transplantation, there is a very small capacity to re-establish neural connections with the host. There is not enough time for the brain to grow new connections before a rhythm is restored. Because rhythms were restored so fast, it was believed that the SCN could communicate in another way.

        1n 1996, Rae Silver’s group at Barnard College, New York, placed a SCN into a semi-permeable capsule before transplanting it. The pores in the capsule were too small to allow neural fibers to pass through, yet the behavioral rhythm as still restored. Now it is clear that the SCN sends information through both neural fibers and unknown diffusible chemicals.

        Insects are known to have multiple clocks throughout their bodies. Drosophila, the fruit fly, has clock genes in its wings, legs, oral areas, and antennae. There have been hints that mammals may also have multiple clocks. Animals who have had their clocks destroyed, still have shown anticipatory behaviors in regards to food, body temperature, and secretion of corticosterone. Ueli Schibler at the University of Geneva, showed that 30-year old fibroblasts (connective tissue cells), could be persuaded to show 24-hour cycles of expression by treating the cells with serum. Cells that had been cultured in isolation, and had absolutely no contact with a SCN, were capable of generating a circadian rhythm.

What researchers have concluded is that in a vertebrate’s body, there are billions of individual clocks, but no distinction between a local clock and the SCN. Transplanted SCN cells are the only things that can restore rhythmicity to an SCN-lesioned animal. Rhythmicity is akin to creating standard time after the advent of the railroad, or when an animal has a SCN. Every town (or part of an insect body) has its own time. When an animal is arrhythmic, there are many local times without a standard.

A rat lives in a situation where it is kept in a dark room and receives food for two hours at the same time every day. It is observed to have a 24-hour feeding rhythm. There is no way to tell if the rat’s behavior is a response to the stimulus of feeding or if the feeding is part of an endogenous circadian rhythm. Is the feeding from an internal or external source?           

        There is, however, a range of entrainment when dealing with cycles that are considerably outside of 24 hours (ex. 22 or 27 hours). If you were to try to entrain, using an abnormal-hour cycle, a rat’s behavior would be irregular. Using non-24-hour cycles to produce abnormal rhythms is called forced desynchrony, which has been used to study human circadian behavior.

        The first person to study entrainment was Christiaan Huygene, a sailor, who was confined to his cabin for two days with seasickness. Inside the cabin, there were two pendulum clocks hanging from the same beam. He noticed how they swung in tune with each other, and if one was disturbed by interference, they would eventually re-establish synchronicity. The vibration from each pendulum was transmitted through the beam so that they were mutually entrained with each other.

        In living organisms, the shift from light to dusk or dawn entrains a circadian rhythm. Other 24-hour factors could also entrain a rhythm such as food availability, humidity, temperature, or social contact. Out of these signals, light is the most stable indicator of the time of day, and is what entrains most clocks. Humans often take half an hour to fully wake up. In the animal world, being half asleep or half awake would be deadly. The precision of entrainment to most of the natural world is of the utmost importance.

        Colin Pittendrigh showed that when an animal is exposed to light when the animal thinks it is day, it has little effect on the clock. Light exposure during the first half of the subjective night causes the animal to delay its daily activities. Light exposure during the second half of the subjective night causes the animal to wake up earlier to advance its daily activities. Light is able to advance or retard a free-running rhythm towards a 24-hour cycle.

        The phase response curve (used to show a behavioral reaction to light) is almost the same for all living organisms. Light in the early morning will almost always delay a sleep/wake cycle. Light in the late evening will advance a sleep/wake cycle.      Masking is the direct effect of light on activity. It was thought that, in mammal eyes, the cells that were used for vision were also used to change the clock. To entrain a circadian rhythm, a relatively long exposure to light is needed

The visual system of a hamster is 200 times more sensitive than the circadian system. Entrainment cannot happen if the exposure is less than 30 seconds. The human circadian system is over 1,000 times less sensitive than the visual system. The retina contains rods and cones, light sensitive photoreceptors. Rods detect dime light while cones detect color and bright light. The projections of retinal ganglion cells form the structure of the optic nerve.

        The SCN receives its retinal projections from the retinohypothalamic tract, formed by a few specialized ganglion cells. These specialized ganglion cells appear to be randomly placed throughout the retina. They represent about one percent of the retina’s total cells. The neurotransmitter glutamate carries photoretinal information to the SCN neurons. The ganglion cells of the visual system send precise, mapped projections to the visual cortex.

        Because a mammal uses its eyes to detect all light, it is possible for it to become circadian blind. Most cold-blooded animals have extra-ocular organs to detect light, and can still entrain to brightness if they lose their eyes.

Dear Diarya,

Thank you for trapping this in my computer.

:(

Kylesa cancelled.

Syntax vs. Semantics

Fuck syntax.