Lecture 21 - Chronobiology Flashcards
Endogenous Biological Rhythms
Circadian Rhythms
Occur about every 24 hours (cort spike in the morning)
Ultradian Rhythms
Occur more frequently than once a day (pulsatile GH release)
Infradian Rhythms
Occur less often than once a day (seasonal breeding)
eg. Circavigintan/Circatrigintan rhythms (menstruation)
Examples of circadian rhythms
rhythm of light, wakefulness, melatonin, and body temperature. These are all involved in sleep, one of our big topics for this final topic that we are covering
Circadian Rhythms affect many physiological functions
This circadian rhythm is really critical for a huge number of functions, from cognition, to motor control, to thermoregulation, to sexual behavior, to digestion. All on this circadian cycle that is driven by hormones. SO what hormone and what system??
The non H-P endocrine connection, we’re finally talking the SC, and melatonin!!
The suprachiasmatic nucleus
One main structure in the CNS responsible for the circadian rhythms: superchiasmatic nucleus (SCN)
Take out the SCN in one animal
Eliminate biological rhythms
Transplant SCN of another animal restores biological rhythms
Rhythm is now the rhythm of the donor
Clock INSIDE the SCN
How does this internal clock coordinate the biological rhythms with the environment?
ie. get IN PHASE with environment
Circadian refers to a daily rhythm and these are governed, maybe unsurprisingly, by the environmental stimuli that signify a day, specifically light.
Ablation and transplant of an SCN
If you have two rats and one sleeps at 7pm while the other has been trained by light to get up then and you transplant the SCNB from one into the other, the animal adopts the rhythm of the transplanted SCN
SCN and Circadian Rhythms
Light reaches the retina
Ganglion cells that contain melanopsin project to the SCN
Retinohypothalamic (RHT) path (light into eye casues activity here)
SCN knows when sun is up
regulate/readjust the cellular clock
The SCN projects multisynaptically to the pineal gland
Activation pineal gland inhibits melatonin
Melatonin alters hormones and behavior
Controls circadian clocks outside of SCN
DARKNESS
Stimulates production of Melatonin
DAYLIGHT
Inhibition of melatonin
Melatonin is sensitive to the “PHOTOPERIOD”
amount of daylight in a given day
What happens in blind people?
No light is transmitted through the retina
SCN pacemaker cannot be synchronized to the light
Blind people do have higher melatonin levels
However, SCN still oscillates at approximately an intrinsic period of 24 hours (endogenous)
WHY?
Supplementary external cues: alarm clock, family, etc…
Free-Running of the Pacemaker (Biological Rhythms)
Great to test this with rats – in blind humans some developmental effect might change the way that melatonin is stimulated, and many blind ppl are not completely blind so that is a confound.
Can take a normally developed rat and put it in a dark room, look how loss of light affects behavior in very controlled environment. Know that there will be no other cues about what the time of day is and no societal rules about when “Shold” be sleeping
See that cycle without any light input is longer than 24hrs, but not much longer, moving about 1 hour forward a day, so internal clock is ~25hrs.
- many of you might have noticed this in your daily life: it is easier to delay going to sleep for a bit than it is to get up earlier in the morning. That is not only explained by “not being a morning person” but is in fact due to our internal clock having a 25 hour length if no external light inputs.
So this seems a bit like weird witchcraft, the body can keep time in the absence of any method to keep time. Something in our cells is like a clock?? Not witchcraft, but SCIENCE, from yout reading for this lecture: how is this sense of time maintained by our SCN and the neurons in this region when there are no internal cues to inform it.
What is the basis of the endogenous clock
Transcription and translation are basis of endogenous clock
Cycle of protein production and degredation = 25hrs
BMAL1 and CLOCK heterodimer
Activate PER and CRY
heterodimer
Suppress their own transcription
PER and CRY degrade, so no negative feedback on CLOCK-BMAL
Restart cycle
Cycle lasts 25 hours
This endogenous clock
Flies, rats, and humans
Conservation of necessary mechanism
Cycle is modulated by epigenetic mechanisms and other post translational modifications to these proteins
Re-entrain SCN after a flight
SCN and pineal gland regulate
peripheral clocks
Sleep Stages
Stage 1 - Beta and theta waves
Stage 2 - K complexes (Spikes)
Stage 3/4 - Delta waves
REM
Usually 4-5 cycles a night. Gets more REM and less deep sleep with each cycle
Body prioritizes deep sleep (needed for physical recovery) over REM (mental recovery) early in case of interruption
Sleep patterns change over the life span
Sleeps serves numerous functions:
allows the body to eliminate waste products from muscles
repair cells
strengthen the immune system
restore neural function and consolidate memory
Operates in this order too, with physical recovery prioritized over psychological recovery.
Start of night predominantly long Stage ¾ to restore physical wear and tear from the day
- something equally important to the understanding of sleep is the hormonal secretion / direct interaction between the HPA axis and the GH secretion - regeneration
Later in night Stage ¾ becomes shorter once physical recovery complete and REM longer as psychological repair, memory consolidation occurs. Sleep deprivation causes significant memory impairment and sleep, even a short nap, has been shown to improve consolidation
Kids need more than adults and adults need more than seniors
Internal Desynchronization
Jet lag
Work shift
Spring fall back
Circadian cycle is endogenous but changes in response to external cues
If normal routine changes, the circadian rhythm may be thrown out of phase
INTERNAL DESYNCHRONIZATION
(Cues from the environment differ from your clock)
Example: JET LAG
Although human behavior adjusts, body temperature and hormone cycles do not
fatigue, low mental performance, and poor motor coordination
Less Symptoms when travelling West
PHASE-DELAY
More Symptoms when travelling East
PHASE-ADVANCE
The problem is worse when travelling east because the body is better able to adapt to a longer day than a shorter one. So, your body adapts better when travelling west because you are extending your day, rather than travelling east, when you are shortening it. In other words, it is easier to delay sleep than force yourself to sleep when you are not ready.
From Work Shift
If you have to do shift work, you might be best off to try and move your shifts forward (to extend your days)
-Increases allostatic load
-many ways designed to combat this eg one week on one shift, one week off, one week on next etc
Spring forward/fall back
Change from standard time to daylight savings time
The rate of traffic accidents increases by more than 5% in the week following the time change
Seasonal rhythms
Biological Rhythms that change every season
Many animals adapt to seasonal fluctuations in environmental conditions, ie. Changes in day length, temperature, food availability and social interactions (reproduction).
- Some animals reproduce in summer, others in winter. Other hibernate in winter, or leave for Florida…
- HOW CAN ANIMALS RECOGNIZE THE OPTIMAL TIME OF THE YEAR TO REPRODUCE, HIBERNATE OR LEAVE TO FLORIDA
Temperature, precipitation, all unpredictable, differ between years
Light is ALWAYS same on March 21, better regulator for seasonal change, plus there is a mechanism for this – light duration influences duration of melatonin realease! Since the body has this all set up maintaining circadian rhythms, makes sense that this same system is utilized to track longer changes that have consistent variations in light
Saw this forever ago in the class that focused on Harris’ research. Could change breeding behavior in ferrets….I believe…. By lengthening light exposure in a day
Seasonal Rhythms and Day Length
WINTER : Long nights and Short Days
Melatonin secreted for LONGER periods of time
SUMMER : Short nights and Long Days
Melatonin secreted for SHORTER periods of time
DURATION of melatonin secretion is what matters, not higher volume, but longer duration
In winter more melatonin > inhibits the MPOA > Lowers GnRH > lowers LH/FSH > Lower E & T > less reproduction in winter
This is dependent on the species, so true for animals with short gestational periods like rodents, who much of this work was done on. Since don’t want babies in time of need then
Need to have babies at the start of spring as food is plentiful in summer
Summary and critical thinking question
Hormones have multiple rhythms…
Pituitary hormones ultradian, circadian and infradian
Cortisol ultradian, circadian, infradian
Gonadal hormones ultradian, circadian and infradian
GHRH/GH circadian rhythm
Feeding hormones diurnal rhythms
What does that look like for the body?
Pulsatile GnRH so many little peaks and troughs, circadian in that peak in the morning along with cortisol, one of the causes of morning wood, and finally there are infradian rhythms in that these hormones peak based on the season when animals WANT to conceive so offspring are born during times of plenty
how can the body make sense out of all the hormonal variations? Not an easy task, considering….
