Circadian Rhythms Flashcards

1
Q

Hamsters in circadian rhythms

A

When you move the dark period slightly the hamster adjusts it’s sleep schedule according to the light, but in constant dim light their circadian rhythm becomes later and later.

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2
Q

How does the rhythm stay constant?

A

Biological clocks

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3
Q

How does the rhythm normally adapt to the 24 hour day?

A

Zeitgebers

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4
Q

Suprachiasmatic Nucleus (SCN)

A

In the hypothalamus

Evidence for its role include lesion studies, recording studies, in-vitro slice studies, transplantation studies.

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5
Q

Molecular mechanisms of the biological clock

A

3 Period genes (Per1-3), 2 Cryptochrome genes (Cry1-2), Clock gene and Bmal1 gene.

Cry, Per1, Per2, and Per3 are transcribed into RNA and leave the nucleus. The concentration increases and protein increases. They bind to each other to create Cry-Per2 and Cry-Per1. The Cry-Per1 goes back into the nucleus and inhibit the transcription. This sets a 24h cycle. Cry-Per2 increases transcription of Bmal1, which binds to the Clock protein. The Bmal1-Clock stimulates the gene transcription of the Per proteins.

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6
Q

Reading the molecular clock

A

SCN activity peaks at middle of subjective day. Gene expression cycles must somehow interact with the excitability of the membrane. Evidence for feedback loops between membrane potential and gene expression.

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7
Q

What causes reduction in the period and cryptochrome proteins?

A

The inhibition of the transcription of per and cry genes, combined with continuous breakdown of the proteins by enzymes.

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8
Q

Outputs of the SCN

A

Many physiological processes are controlled by the SCN.

We focus on the sleep-wake cycle and synchronising other clocks in the body through melatonin

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9
Q

Sleep-wake step by step

A

SCN excites the Ventral Subparaventricular Zone (vSPZ) through synapses and chemical signals.
vSPZ excites the Dorsomedial Nucleus of the Hypothalamus (DMH)
The DMH inhibits vIPOA and excites the lateral hypothalamus.
Circadian control of sleep/wake cycle.

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10
Q

Hormones

A

Go through the bloodstream, and acts globally. The effects can be varied, depending on the hormone/receptor combination.

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11
Q

Melatonin Day vs Night

A

When the SCN suppresses activity in the sympathetic Superior Cervical Ganglion the pineal gland is inhibited from releasing melatonin.

During subjective night, sympathetic activity releases NA into pineal gland, triggering de novo synthesis of melatonin into the blood stream.

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12
Q

Melatonin In The Body

A

Melatonin circulates in the body and binds to MT receptors.
It effects the entrainment of circadian clocks in tissues where they exist.
Length of melatonin secretion also serves as a seasonal signal.

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13
Q

Zeitgebers

A

They entrain the internal rhythm with the external rhythms.

External rhythms include light, food and sounds.

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14
Q

What happens when a bright light is shone deep in the sleep cycle?

A

The next sleep cycle gets shortened.

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15
Q

Why is there a delayed phase response?

A

Melanopsin sits in the retina and detects light and changes the firing potential of the retinal ganglion cells, which is communicated to the SCN. Another branch goes to the Lateral Geniculate Nucleus which goes back to the SCN.

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16
Q

What happens when information comes through the retinal hypothalamic tract?

A

RHT axons synapse onto SCN using glutamate onto NMDA-receptors.
Increase in intracellular calcium and induction of 2nd messenger cascades.
Transcription of clock genes (eg per) is unregulated

17
Q

Effects on the melatonin receptors in the SCN

A
  1. Acute inhibitory effect on neuronal firing.

2. Phase-shifting effect of rhythm (especially within 30 minutes of onset of subjective night)

18
Q

Does melatonin effect Per and Cry

A

Melatonin does not affect transcription of Per and Cry directly, but does interact with the cycle via other mechanisms.

19
Q

Jet-lag

A

Disparity between internal and external rhythms
Different rhythms in the Cry are out of synch with each other
Disappears slowly over time by entrainment to the new environment
Jet lag can be treated with melatonin