PSB3340 - Sleep: Biological Rhythms

Circadian rhythms

functions of a living organism that display a rhythm of about 24 hours, including physical, mental, behavioral, and biochemical changes

Diurnal

active during the light (day) e.g. humans, dogs, elephants

Nocturnal

active during the dark (night) e.g. bats, skunk

Crepuscular

active during twilight, the time shortly before sunrise and after sunset (e.g. house cats, rabbits, deer)

How do we generate circadian rhythms?

Through an endogenous (i.e. internal) clock, or internal timing mechanism.

Zeitgeber

rhythmically occurring natural phenomenon that acts as an external cue to synchronize the endogenous/circadian rhythm

What are some common Zeitgebers?

Common “time giver” cues include light and food

Entrainment

process of synchronizing a rhythm, particularly the circadian rhythm, using an external stimulus or rhythm (e.g. light)

In hamsters and humans, under dim illumination, the internal clock follows a…

~25 hour cycle

Nocturnal hamsters experiment

Changing the times of lightness and darkness changes the pattern of activity.

Removing the zeitgeber, i.e. external cue, of changing light conditions results in animals becoming subject only to internal timing mechanisms

Free running

animals are only subject to internal timing mechanisms, in the absence of a (e.g. light) zeitgeber

Suprachiasmatic Nucleus (SCN)

Tiny subregion of the hypothalamus that is located above the optic chiasm and is the brain’s master biological clock. Regulates circadian rhythms, as proven by frankenhamsters.

Circadian rhythm experiment in Hamsters

Tau genetic mutation causes hamsters to have a free-running rhythm of 22 hours (1 copy) or 20 hours (2 copies). Transplanting SCNs from double tau carrying hamsters into normal (25 hour clock) hamsters produce hamsters with a 20 hour clock.

Retinohypothalamic pathway

Light information goes from the retina and to the hypothalamus, reaching the SCN. This route is separate from vision’s.

Intrinsically photosensitive retinal ganglion cells (ipRGCs)

Light transmitting cells are ganglion cells, not rods or cones, that contain and use the photopigment melanopsin which is sensitive to light, especially blue.

Opsin

retinal protein, like rhodopsinH

How can blind people and animals have circadian rhythms?

ipRGCs contain melanopsin and are still transmitting light information to the SCN, even in the absence of rods or cones.

Other functions of ipRGCs

Project to the brainstem (pretectal nucleus and the Edinger-Westphal nucleus) and help control the pupillary light reflex (PLR), which is the rapid rapid constriction of the pupil to protect retina from intense light energy

Molecular clock

refers to the “ticking” of the biological clock in the SCN that is measured by how long it takes to produce and degrade a set of proteins

Two main proteins made by SCN cells

Clock and Cycle proteins, which bind together to form a dimer

BMAL1

the mammalian version of the Cycle protein

What is the function of the Clock and Cycle protein dimer (Step 1: dimerization)?

(Step 2) The dimer promotes (+) mRNA transcription, resulting in the creation of period (PER) and cryptochrome (CRY) proteins in the cytoplasm

What is the function of the PER and CRY proteins (Step 3)?

PER and CRY proteins dimerize into a complex that inhibits (-) the activity of clock/cycle proteins (negative feedback).

How does cycle conclude and then restart? (Step 4)

As long as PER/CRY proteins are active, Clock/Cycle proteins are inhibited. Once PER/CRY proteins begin to degrade overtime, this allows for Clock/Cycle to increase and therefore increase transcription of PER and CRY.

How long does the Clock/Cycle and PER/CRY process take?

About 24 hours

What kind of feedback is this cycle?

Negative feedback. PER and CRY proteins, produced at the end of the cycle, move back to the nucleus and inhibit Clock and Cycle (or BMAL1) which are the initiators of transcription.

What is the role of glutamate in entrainment of the molecular clock and day-night cycle?

In mammals, retinal ganglion cells are depolarized, or excited, by light (unlike photoreceptors) which they detect with melanopsin.

ipRGC action potentials then release glutamate onto SCN neurons, which promotes Per production. This results in the synchronization (or entrainment) of the molecular clock and the animal sleep/wake cycle with light levels from the external environment.

Larks vs Night Owls

People who feel more energetic in the morning often have different alleles of the per gene that those who are more energetic at night

Chronotype

one’s natural preference for sleep and wake times, that is, one’s internal clock defining them as an early bird or night owl; important part of broader circadian rhythm

The Morningness-Eveningness Questionnaire (MEQ)

can help assess chronotype to determine if you are a night owl or early bird

Bedtimes as they relate with where you live in the U.S.

People on the west coast tend to got to bed later that those on the east, which follows the pattern of sunlight. Note that bedtimes don’t perfectly track patterns of sunlight

Infradian rhythm

biological rhythms longer than a day, such as reproductive cycles; less than once per day

Ultradian rhythm

rhythms shorter than a day, such as bouts of activity, feeding, hormone release

Circannual rhythm

rhythm that has a period of 365 days and is a type of infradian rhythm

Components of Circannual rhythm

Present in seasonal animals in isolation with free running annual rhythms, which seem to be endogenous. The mechanism is separate from the SCN, as lesions do not affect seasonal mating behavior of weight changes, and involves melatonin.

Melatonin and light

Light information from the retina to the SCN suppresses the pineal gland from releasing the hormone melatonin, which is very active (in large amounts) at night and in the winter. Melatonin has a not well understood influence on circadian rhythms.