Curt Richter (1967) introduced introduced the concept that the brain generates its own rhythms - a ____ ____ - and he reported that the biological clock is insensitive to most forms of interference.
The circadian rhythm remains surprisingly steady despite food or water deprivation, X-Rays, tranquillisers, alcohol, anaesthesia, lack of oxygen, most kinds of brain damage, or the ____ of ____ ____.
removal of endocrine organs
The biological clock depends on part of the hypothalamus, called the ____ ____ or SCN.
The SCN provides the main control for the circadian rhythms for ____ and ____ ____, although several other brain areas generate local rhythms.
sleep and body temperature
After damage to the SCN, the bodies rhythms become ____.
The SCN generates circadian rhythms itself in a ____ controlled, unlearned manner.
If SCN neurons are disconnected from the rest of the brain or removed from the body and maintained in tissue culture, they continue to produce a circadian rhythm of ____ ____.
Even a single isolated SCN cell can maintain a circadian rhythm, although ____ among cells sharpen the action of the rhythm.
The SCN is located just above the ____ ____.
A small branch of the optic nerve, known as the ____ ____, extends directly from the retina to the SCN. Axons of that path alter the SCN's settings.
The retinohypothalamic path to the SCN comes from a special population of retinal ganglion cells that have their own photopigment, called ____, unlike the ones found in rods and cones.
These special ganglion cells in the retinohypothalamic path receive some input from rods and cones, but even if they do not receive that input, they respond directly to ____.
These special ganglion cells in the retinohypothalamic path respond to the overall ____ amount of light, not to instantaneous changes of light. The average intensity over minutes or hours is exactly the information the SCN needs to gauge the time of day.
Many people who are ____ because of damage to the rods and cones nevertheless have enough input to the melanopsin-containing ganglion cells to entrain their waking and sleeping cycle to the local pattern of sunlight.
It was formally puzzling that bright light aggrevates migraine headaches even for many blind people. The explanation is that melanopsin-containing ganglion cells send input to the ____ ____, which is part of the pathway producing pain in migraines.
Someone with no input to the visual cortex, and therefore no conscious vision, can nevertheless have ____ excitation in the thalamus.
Research on production of the circadian rhythm began with insects. Studies on the fruitfly ____ from several genes responsible for a circadian rhythm.
Two of these genes found in the fruit fly, known as period (abbreviated per) and timeless (tim), produced a proteins ___ and ___.
PER and TIM
The concentration of these two proteins, which promotes ____ and ____, oscillates over a day, based on feedback interactions among several sets of neurons.
sleep and inactivity
Early in the morning, the messenger RNA levels responsible for producing PER and TIM start a low concentrations. As they increase during the day, they increase synthesis of the proteins, but the process takes time, and so the protein concentrations lag ____ ____.
As the PER and TIM protein concentration is increased, they feedback to inhibit the genes that produced the messenger RNA molecules. Thus, during the night, the PER and TIM concentrations are ____, the messenger RNA concentrations are _____. By the next morning, PER and TIM protein levels are low, and the cycle is ready to start again.
high : declining
In addition to the automatic feedback, ____ activates a chemical that breaks down the TIM protein, thereby increasing wakefulness and synchronising the internal clock to the external world.
____ have three versions of the PER protein and several proteins closely related to TIM and the others found in flies.
Mutations in the genes producing PER proteins lead to alterations of ____ ____. People with a particular PER mutation have been found to have a circadian rhythm shorter than 24 hours, as if they were moving about time zone West every day.
Most people with the sleep abnormality suffer from ____. Sleep impairments and depression are closely linked.
The SCN regulates waking and sleeping by controlling activity levels in other brain areas, including the ____ ____, an endocrine glance located just posterior to the thalamus.
The pineal gland releases the hormone ____, which influences both circadian and circannual rhythms.
The pineal gland secretes melatonin mostly at ____, making a sleeping at that time. When people shift to a new time zone and start following a new schedule, they continue to feel sleepy at their old times until the melatonin rhythm shifts.
Melatonin secretion starts to increase about __________ before bedtime. Taking a melatonin pill in the evening has little effect on sleepiness because the pineal gland produces melatonin at that time anyway. However, people taking melatonin at other times become sleepy within two hours.
two or three hours
Melatonin pills are sometimes helpful when people travel across ____ ____ or for other reasons need to sleep at an unaccustomed time.