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332: Neurobiology > 4. Circadian Rhythms > Flashcards

4. Circadian Rhythms Flashcards

1
Q

what is the circadian clock

A

an endogenous molecular pacemaker that drives daily rhythms affecting physiology, biochemistry and behaviour

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2
Q

what species were the first clock mutants isolated in?

A

drosophila

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3
Q

what is the most conserved mechanism of the circadian clock

A

the negative feedback loop

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4
Q

what is the main way to measure the circadian clocks in drosophila

A

locomotor activity

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5
Q

what does free run mean

A

the biological rhythm exists without any external input or cues

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6
Q

what does entrainment mean

A

the biological rhythm is synchronised to an external oscillations

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7
Q

give an example of an external oscillation that entrains biological rhythms

A

the light/ dark cycle

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8
Q

at what point in the day are flies the most active

A

at dawn - they anticipate the light
Flies are also active at dusk

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9
Q

what was the first gene identified that could affect circadian rhythms

A

period

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10
Q

what happens in Per0 mutants

A

produces arrhythmicity

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11
Q

what happens in PerL mutants

A

produced long period rhythms of 28 hours

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12
Q

what happens in PerS mutants

A

produced short period rhythms of 19 hours

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13
Q

what 4 properties define circadian rhythms

A
  1. oscillations free run under constant conditions, indicating the presence of a self-sustaining clock
  2. the clock driven events recur approximately every 24 hours
  3. rhythms are entrained by sun-driven changes in light or temperature
  4. the period of the clock is remarkably stable over a wide temperature range.
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14
Q

circadian systems are organised into 3 main parts, what are the three parts?

A

the core clock
the input pathways
the output pathwyas

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15
Q

what is the function of the input pathways

A

synchronise the clock to its environment

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16
Q

what is the function of output pathways

A

transmit information to temporally organise behaviour and physiology

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17
Q

what is the function of the core clock

A

keeps the time

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18
Q

what degrades period, how?

A

double-time

via phosphorylation

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19
Q

period and timeless are under the control of a promotor, what is the name of the element of this promotor

A

E-box element

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20
Q

what happens when clock and cycle bind to the E-box

A

drives the production of per and Tim mRNA

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21
Q

name the 5 things that modify period and timeless proteins before it dimerises

A

doubletime
casein kinase 2
shaggy
phosphates: PP2A and PP1

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22
Q

what happens when period and timeless dimerise

A

they can enter the nucleus where they are able to inhibit clock and cycle proteins from binding to the E-box = suppressing their own expression

= negative feedback loop

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23
Q

describe the processes occurring in a clock cell: in the morning

A
  • all timeless has been degraded
  • period is no longer protected in the dimer so is also degraded by hyperphosphorylation by double-time
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24
Q

describe the processes occurring in a clock cell: at mid-day

A

no inhibition of per/Tim transcription
Clk and Cyc bind to the E-box and mRNA content rises
NO PROTEIN

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25
Q

why is no protein content of period or timeless produced at mid-day

A

timeless protein is degraded by light

and no period as it is not protected by timeless

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26
Q

describe the processes occurring in a clock cell: at dusk

A

timeless is no longer degraded by light
mRNA = proteins
these proteins dimerise after being modified by a host of factors.

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27
Q

describe the processes occurring in a clock cell: at midnight

A

dimers enter the nucleus
period associated with clock = double-time phosphorylates clock
phosphorylation prevents clock from binding to the E-box
= inhibits the transcription of per/Tim

all remaining protein content is degraded = repression is released

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28
Q

define exogenous Zeitgeber

A

external cues that help regulate the internal biological clock

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29
Q

name 2 exogenous zeitgebers

A

light
temperature

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30
Q

how does light reach clock neurons

A

via photoreceptive organs containing rhodopsins

31
Q

what organs contain rhodopsin in flies

A

ocelli and HB-eyelets

32
Q

what is cryptochrome

A

a blue light photopigment that is activated by light

33
Q

what does activated cryptochrome degrade

A

timeless

34
Q

what happens to cyrptochrome after timeless has been degraded

A

Jet Lag binds to Cry = degradation

35
Q

how does cryptochrome degrade timeless

A

binds to timeless and recruits F box protein Jet Lag = targets Tim for ubiquitination and degradation

36
Q

what happens in flies with a mutation to jet lag

A

cant adapt to different light/ dark cycles

37
Q

which gene and protein is evolutionarily conserved across mice and flies

A

clock genes / proteins

38
Q

what do clock neurons regulate in a fly

A

locomotion

39
Q

how many neurons in the fly brain regulate locomotion

A

20-30

40
Q

what neurons promote morning activity

A

S-lateral neurons

41
Q

what neurons promote evening activity

A

LNds
s-LNv

42
Q

what neuron peaks at dusk

A

LNd

43
Q

what neuron peaks at dawn

A

s-LNv

44
Q

what neurons promote both morning and evening activity

A

DN1s

45
Q

what happens to DN1 neurons in the evening when there is high light

A

they have low output

  • similarly when there is low light in the evening = they have strong output
46
Q

what does PDF stand for

A

pigment dispersing factor

47
Q

what is the role of PDF neurons

A

synchronise clock neurons in the absence of light

48
Q

what are PDF neurons termed

A

internal zeitgebers

49
Q

name three things that sleep is important for

A

cognition
immune function
physiological and neural homeostasis

50
Q

what human gene underpins ‘night owls’

A

CRY1

51
Q

describe sleep in tribes

A

tribes exhibit natural variation in chronotype (genes which dictate sleeping patterns) - this is driven by selective forces so that the entire tribe does not sleep at the same time

= variation in sleep schedules can be beneficial in preventing predation.

52
Q

name 3 tools used to measure sleep in drosophila

A

infrared detection (to measure locomotion)
neurophysiology (using electrodes)
beam crossings

53
Q

how do beam crossings work to monitor sleep in drosophila

A

an infrared beam is placed in a tube with a fly
the number of times the fly crosses the beam is counted by the DAM (drosophila activity monitor)

  • able to distinguish periods of sleep from periods of activity
54
Q

what happens when light activates I-vLNs?

A

they release PDF onto other s-vLNs that then project to other clock neurons or brain regions to increase motor activity

55
Q

name one of these brain regions that s-vLNs project to?

A

ellipsoid bodies

56
Q

what is the role of ellipsoid bodies

A

motor control

57
Q

what happens to these neural pathways at sleep

A

GABAergic sleep-promoting neurons inhibit these pathways via GABA activity which reduce alertness and arousal

58
Q

what are the 3 neuronal sleep centres in flies

A

Kenyon cells (MB)
fan-shaped bodies
ellipsoid bodies (EB)

59
Q

name 2 neuromodulatory neurons that regulate sleep centres

A

DA neuorns
dorsal paired medial neurons

60
Q

what is the response to sleep deprivation caused by caffeine

A

sleep rebound = an increase in sleep to make up for the lost sleep

61
Q

what is the response to sleep deprivation caused by failed copulation or starvation

A

no sleep rebound = overrides homeostatic mechanisms to feed and breed which are essential to survival - a likely evolutionary process

62
Q

what happens to the activity of starved flies? why?

A

increased locomotor activity - which is likely to enable them to discover new food sources.

63
Q

ER: what is evidence for the role of the SCN?

A

DeCoursey et al. 2000

destroyed the SCN connections in 30 chipmunks - they were returned to their natural habitat and observed for 80 days

results: their sleep wake cycle disappeared and a significant proportion were killed by predators by the end of the study.

64
Q

in humans what is the endogenous pacemaker and where is it found

A

the suprachiasmatic nucleus of the hypothalamus

65
Q

how many groups of clock neurons in flies and what are they named after

A

7 major groups named after their anatomical position

66
Q

what also expresses clock proteins in fly brains

A

a few hundred glial cells.

67
Q

ER: temperature can entrain flies, a change of how many degrees is sufficient to adapt a flies circadian clock

A

3 deg c change is sufficient to change the circadian rhythm

68
Q

what is the mechanism of how temperature entrains the clock

A

nobody knows - it has not yet been discovered

69
Q

temperature can entrain the clock under constant light conditions, what does this mean?

A

suggests there is an override of light dependent degradation of timeless

70
Q

where is temperature perceived, what is the evidence

A

in the tissues and not in the CNS

evidence:
- isolated body parts are able to perceive temperature = temperature reception is tissue- autonomous

-isolated brain are not able to synchronise to temperature cycles

71
Q

what gene is involved in circadian temperature reception

A

norpA gene

72
Q

what does norpA encode

A

phospholipase C

73
Q

how do we know norpA is involved in temperature reception

A

animals with mutated norpA are not able to synchronise to temperature cycles.

74
Q

describe Siffre (1962) case study

A

spent 6 months in a cave - with no exposure to light (an exogenous zeitgeber)

= his circadian rhythm remained consistent at 24 hours and 30 minutes

  • supports the fact that circadian rhythms free run under constant conditions

332: Neurobiology (15 decks)

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