Lectures 6-8

Question 1

The suprachiasmatic nuclei (SCN) contain a ….

Answer 1

…..circadian oscillator that functions as the major biological clock

Question 2

How many GABAergic neurons form the SCN?

Answer 2

~ 10,000 per SCN nucleus

~20,000 total

Question 3

These findings suggest that the SCN has …..

Answer 3

inherent time keeping capacity

Question 4

The SCN continues to oscillate outside of the brain

Answer 4

Individual SCN neuron oscillations can also be recorded.

Question 5

What Neurotransmitter does the SCN primarily secrete?

Answer 5

GABA

Question 6

GABA

Answer 6

γ-Aminobutyric acid,
gamma-Aminobutyric acid

The chief inhibitory neurotransmitter in the mammalian CNS.

GABA does not excite neurons; it’s a negative regulator.

It plays the principal role in reducing neuronal excitability throughout the nervous system.

Question 7

One of the first experiments that tested the transcriptional basis of rhythm generation

Answer 7

Bulla gouldiana (bubble shell gastropod-native to west coast)

Tested the effects of protein synthesis inhibitors in tissue taken from the eye-antennae structure. They wanted to stop protein synthesis and assess the effect on the firing properties recorded in the nerves of the eye.

Used Anisomycin and Cycloheximide to inhibit the protein synthesis. Potent toxins.

Increasing these inhibitors correlated with lengthened tau (longer periods), as protein production was slowed.

Increasing protein inhibitor concentration increased tau length; the period of the rhythm became longer and longer as protein production was slowed down by the chemicals. Eventually, circadian boundaries were lost.

Results suggests the gene expression (i.e., protein synthesis) determines tau length. No consolidation of rhythms.

Question 8

How might a biological system generate at cellular-level
rhythm?

3 Hypotheses on how the SCN built a cellular oscillator via feedback loops.

Answer 8

Membrane Excitability Oscillation

Redox Oscillation

Transcriptional-Translational Oscillation

Question 9

How might a biological system generate at cellular-level
rhythm?

Correct Answer:

Answer 9

Transcriptional-Translational Oscillation

Question 10

Gene expression is an essential component of the circadian clock timing mechanism

Answer 10

Low-level. (Smaller amounts of protein inhibitor.)
Protein synthesis inhibition:
Reduced periodicity (tau).

High-level persistent. (Excess inhibitor.)
Protein synthesis inhibition:
The clock stops and
resumes at a different phase.
No consolidation of rhythms.

Question 11

Numerous studies built the case for transcriptional rhythms as a key underlying mechanism in the generation of a circadian oscillation

Answer 11

…

Production of peptides oscillates throughout the circadian cycle.

Question 12

Circadian clock model building:

Answer 12

Based on a transcriptional feedback loop

Question 13

Membrane Excitability Oscillation

Answer 13

rhythm in the firing properties of the neurons.

Not The Real Cause

Question 14

Bulla gouldiana

bubble shell gastropod-native to west coast

Answer 14

simple model system first used to understand and model biological clocks

They used the firing properties of neurons in the eyes of the gastropod, and tested the effects of protein synthesis inhibitors.

“We know report evidence for a phase-specific requirement for protein synthesis in maintaining pacemaker motion: disruption of protein synthesis ‘stops the clock,’ which resumes its motion only upon removal of the protein synthesis inhibitor.”