SAMPLE FINAL PLUS PRACTICE MIDTERMS Flashcards
Bright daylight can influence:
a. Amount of melatonin secreted in humans
b. Phase of onset of melatonin secreted in humans
c. Phase of onset of activity in hamsters
All of the above
If free running hamsters in constant lighting conditions are given a light pulse during the middle of the subjective day, this will:
Have little or no effect on the activity rhythm
Evidence from Hamsters suggests that the activity-rest circadian rhythm can be entrained to any period within:
18-26 hours
Biological rhythms observed in constant environmental conditions are said to be __________.
Free-running
If an appropriate __________________ is given, the rhythm is said to become _________________ to environmental conditions.
Zeitgeber, Entrained
In an early experiment by de Mairan, a mimosa plant was placed in a dark cabinet and temperature was held approximately constant.
The plant continued to show a daily rhythm of leaf movements, with leaves open during the day and folded at night.
This result indicates most conclusively that:
the natural daily rhythms of light and temperature are not required for rhythmic leaf movements
An experiment by de Candolle showed that the rhythmic leaf movements of the mimosa plant continued in constant darkness with a period length that was not exactly 24h.
This type of observation helped to convince biologists that:
some daily rhythms are driven by internal, self-sustained oscillators
A common feature of circadian, circannual, circatidal, and circalunar rhythms is that all of them:
are related to geophysical rhythms that may have some importance to organisms
As compared to homeostatic processes, biological rhythms seem to be much less dependent on:
internal negative feedback mechanisms
For a Nocturnal animal that is free-running under constant conditions, the beginning of the active phase (locomotor activity) corresponds approximately to:
beginning of subjective night (??)
The term “temperature compensation” is most clearly illustrated by the observation that:
mean environmental temperature has little effect on taudd
Differences between individuals of a species with respect to tau:
a. may result from genetic differences
b. may be a result of different photoperiod histories of the individuals
c. may be related to age
d. do not exist
e. “a” , “b”, and “c”
e.
“a” , “b”, and “c”
Rodents are most likely to become arrhythmic (non-rhythmic) when exposed to:
continuous light (LL)
If you wanted to estimate the limits of entrainment to light/dark cycles for a particular species, which of the following would provide helpful information:
the phase response curve and tau
For people on a normal day-night schedule, cortisol levels peak in the______________ and are lowest in_________________.
Early morning; early evening
The last link in the pathway to the pineal gland comes from the:
Superior cervical ganglia
All of the following are involved with mammalian photoperiodism except the
a. Pineal gland
b. Suprachiasmatic nucleus (SCN)
c. GnRH neurons
d. Hippocampus
Hippocampus
The Aschoff Rule states that
light intensity affects the period of a rhythm
A phase response curve (PRC) best describes
a rhythm’s entrainment properties
Which of the following exhibits clock properties in birds?
a. Suprachiasmatic nucleus
b. Pineal gland
c. The retina of the eye
d. both a and b
e. a, b, and c
d. both a and b
Suprachiasmatic nucleus,
Pineal gland
In general, seasonal reproduction in various avian and mammalian species is usually regulated by one of the following factors, but NOT
a. photoperiod
b. food availability
c. a circannual rhythm
d. temperature
Temperature
The critical feature of pineal gland function that causes short-day-induced gonadal regression in rodents is:
the duration of the daily melatonin rhythm
Biological clocks are involved in all of the following events, EXCEPT
a. the sun-arc hypothesis
b. photoperiod time measurement
c. night orientation to star patterns
d. the hibernation cycle of the ground squirrel
e. the feeding cycles of voles
night orientation to star patterns
Infradian rhythms refer to those rhythms with a period
that is more than 24 hours
What is the single most defining characteristic of a true biological rhythm?
that it is self sustaining
Which region of the mammalian brain is viewed as the master clock that organizes all circadian rhythms?
suprachiasmatic nucleus
Which of the following list of biological rhythms is ordered from most frequent (shortest) to least frequent (longest)?
ultradian, circadian, infradian, circannual
What is photoperiodism?
the ability to use day length to time annual cycles
List 5 characteristics of biological clocks:
…
Describe the two ways that biological clocks allow animals to adapt to temporal fluctuations:
…
What is the relationship of the circadian system to the ovulatory cycle in rats and hamsters?
…
Briefly describe and evaluate the experimental evidence that the SCN is an important neural clock in mammals.
In the second part of your answer propose what you think is the most important next step to understand SCN function as a neural pacemaker.
Defend your choice and provide a brief experimental approach as to how you would address the problem.
…
VIP-expressing neurons are found in which region of the SCN?
Core
- weak rhythm
TRUE or FALSE?
Period 1 and Period 2 dimerize to drive the expression of Clock and Bmal1.
FALSE
2-Deoxyglucose labeling was used to determine ________.
The locus of the master clock
The Bulla gouldiana model system was used to show that ________ .
Protein synthesis rates set clock period length
The E-Box binds to which transcription factor?
CRY
ERK
Leucine Zipper
CREB
none of the above
Which of the following approaches was used to test Period 1 and Period 2 functionality in the circadian clock?
Gene Knockout
What neurotransmitter is expressed in both the core and the shell of SCN
GABA
ENU causes which type of mutations?
A to T
In the absence of any information regarding the molecules underlying a physiological process, what genetic approaches could be used to begin to identify the relevant genes?
Forward genetics
Which region of Clock protein allowing for protein‐interactions?
PAS domain
Within the core clock transcription/translation feedback loop, Period protein would be considered which type element?
Negative element
Clock mutation heterozygous mice exhibit what circadian phenotype?
Long rhythm
What was the effect of the Tau mutation on period length?
Shorter
Which of the following compounds inhibit sleep?
orexin
Loss of orexin neurons is associated with
daytime sleepiness
What would be the effect of 30 minutes of light on a hamster’s wheel running behavior if the hamster was kept in total darkness and the behavior was free-running?
It would depend on when in the animal’s subjective night that the light was turned on.
What would one expect to happen if the zeitgeber was removed from a group of rats?
a. there would be no effect of removing the zeitgeber
b individual rats would be active consistently earlier or later every day
c. there would be a phase advance in the rats’ activity onset
d. there would be a phase delay in the rats’ activity onset
Individual rats would be active consistently earlier or later every day.
Which of the following statements is false?
a. melatonin at high doses (>100 mg) is toxic
b. the precursor for melatonin is serotonin
c. melatonin may inhibit aging
d. melatonin activates glutathione peroxidase
melatonin at high doses (>100 mg) is toxic
If a male hamster is kept in short days (10 hrs light & 14 hrs dark) indefinitely, it will
spontaneously exhibit testicular growth after several months
Mammals, flies, fungi and cyanobacteria all have transcriptional clocks that work in a similar way, although has a different pair of genes. In mammals, the genes are
BMAL/Clock
Per and CRY
Photoperiodism in different organisms affects the timing of different physiology, but the one that is most universally affected is:
reproduction
“Photo” of photoperiodism refers to :
light
If you had a plant that was being consumed by a fast reproducing bug called bugerosus, and you found on the internet that the critical dark period for bugerosus’ reproductive cycle is 5 hours, then you could conceivably control the bug by:
Leaving the lights on for 20 hours each day and off for 4 hours
The testes eventually develop in male hamsters even if they remain in constant dark condition. This observation demonstrates that testicular development is also controlled by:
a circannual rhythm.
Rodents are most likely to become arrhythmic (non-rhythmic) when exposed to:
continuous light (LL)
If you wanted to estimate the limits of entrainment to light/dark cycles for a particular species, which of the following would provide helpful information:
the phase response curve and tau
A common feature of circadian, circannual, circatidal, and circalunar rhythms is that all of
them:
Are related to the period of the earth’s rotation about its own axis
Deletion of the clock gene has what effect on Period 1 expression.
Repressed
The Period mutation was first characterized in _______ .
Drosophila
Which effect would blocking Period protein nuclear translocation have on the Period gene expression?
suppressed expression
Which effect does the Tau mutation have on casein kinase 1 activity?
stimulates
PAS Domains are found in which of the following proteins:
a. period
b. clock
c. BMAL
d. none of the above
e. all of the above
all of the above
In butterflies, cryptochromes were shown to function in:
magnetic field-based navigation
What finding suggested that clock cell communication is essential for the phase-coherent output of the SCN?
the varied periodicity of isolated SCN neurons
VIP binds to what type of receptor?
G-protein coupled receptor
Bmal1 and Clock:
drive the rhythmic expression of clock output genes
Which two intracellular signaling effectors are NOT downstream of VIP in the SCN?
PKG and AMPK
Which two intracellular signaling effectors are downstream of VIP in the SCN?
a. calcium
b. PKG
c. AMPK
d. cAMP
calcium, cAMP
The retinohypothalamic nerve terminal is:
glutamatergic
Early life circadian rhythms can be restored to pups of SCN-lesioned dams with the administration of:
a. melatonin
b. dopamine receptor agonists
c. temperature fluctuations
d. a and b
e. all of the above
a and b
melatonin and dopamine receptor agonists
An intact maternal SCN is necessary for all of the following EXCEPT:
a. rhythms of 2DG in the fetal SCN
b. rhythms of NAT activity in the 10 day old animal
c. the phase of entrainment of the pups
d. the cycle length (tau) of the pups
e. intact maternal SCN is necessary for all of the above
d. the cycle length (tau) of the pups
TRUE or FALSE?
Cycling clock genes can be detected in fetal rat SCN by prenatal day 10.
false
TRUE or FALSE?
Cycling clock genes can be detected in fetal rat SCN by embryonic day 19.
true
Circadian rhythmicity can be detected in fetal animals by all techniques EXCEPT:
a. measuring wheel running activity
b. assessing radioactive glucose uptake in the SCN
c. Measuring N-acetyl transferase expression
d. assessing clock gene expression
e. all of the above
measuring wheel running activity
Which 2 intracellular signaling pathways were shown to oscillate in the SCN:
a. PKG
b. PKM
c. cAMP
d. cGMP
e. cTKP
f. calcium
g. potassium
h. nitrogen
cAMP and calcium
How do oscillations in intracellular signaling pathways regulate the core molecular oscillations?
amplification of Period 1 transcription
Light pulses delivered at the following times have what effect of circadian clock phase?
Early subjective night: Phase Delay
Late subjective night: Phase Advance
Mid-subjective day: Nothing
Photic stimulation during the mid-subjective day has what effect on MAPK expression?
no effect
List 3 effects that constant light has on overt rhythms -
- arrhythmia
- tau lengthens
- split rhythm
At the level of the molecular clock, photic resetting is caused by a rapid increase in the expression of:
???!!
Constant light-induced splitting of locomotor activity results from:
????!!
Phase of activity nrhythms in pups match that of the mother except when the mother is __________ .
SCN lesioned
Disruption of cAMP levels had what effect on Period 1 luciferase rhythms.
Damped.
The melanopsin receptor is activated by which light color?
??!?!!
Melanopsin is expressed in which type of cell?
Retinal ganglion cells
Which transcription factor couples the MAPK pathway to the core molecular clock?
a. E-Box
b. CREM1
c. NPAS
d. CREB
e. TORC1
f. Bmal1
g. Clock
CREB
Blind-Sight refers to ….
the ability to use non-image-forming visual circuits to navigate in space.
A novel wheel triggers resetting of the circadian clock by triggering.
…..???!!!
In the experiments that examined MAPK signaling and light-evoked click resetting, U0126 was used to
…..???!!!
Dopamine agonists induce _______ expression in the SCN.
It therefore acts as a signal of _________ .
Dopamine agonists induce c-fos expression in the SCN.
It therefore acts as a signal of daytime.
TRUE or FALSE?
Infusing high continuous levels of GnRH produces greater production of LH and FSH than intermittent infusion.
FALSE
The best evidence that SAD does not merely reflect the “holiday blues” is:
the symptoms are 6 months out of phase in people inhabiting the southern hemisphere
GnRH infused in which pattern will give the maximal pituitary gonadotropin response?
Pulsatile administration
Circadian rhythms do not appear to mediate the preference for song length in Drosophila
because
Per mutations do not change song preference despite altering song production and
circadian rhythms
TRUE or FALSE?
There are more traffic accidents the day after both the spring and fall time shifts for day lights savings.
FALSE
All of the following appear to be able to synchronize circatidal rhythms in crabs except:
Inundation
Heavy water (D2O) alters
Circadian but not ultradian rhythms
The apparent role of the-SCN axis in the control of growth hormone release is
When the SCN is lesioned GH release continues but is no longer synchronized to the light/dark cycle
The human menstrual cycle likely evolved to be the same length as the lunar cycle because….
***There is no apparent relationship between the length of the lunar and menstrual cycles.
OR
It would be advantageous to be most fertile when the moon is full so it is easier to find
Seasonal affective disorder is characterized by all of the following except
- impaired retinal function
- shorter melatonin duration
- seasonal patterns of recurrence
- treatment with light or SSRIs can relieve symptoms
impaired retinal function
Heart attacks and strokes are most common in the
9am
Nuclear hormone receptors act in an ‘accessory loop’ to influence clock and metabolic function:
REV-ERBs (repressors)
RORs (activators)
They bind retinoic acid-related orphan receptor response elements (ROREs) at the Bmal1 promoter.
RORα and REV-ERBα respond to metabolic status and are targets of CLOCK:BMAL1
REV-ERBα is induced during adipogenesis
Deletion of REV-ERBα leads to altered metabolism and obesity.
Cold stress rapidly downregulates Rev-erbα
Rev-erbα orchestrates the daily rhythms of body temperature
Nuclear receptors both sense and respond to the environment!
Metabolic status and the circadian clock are fundamentally and dynamically linked
Nampt
important for cellular metabolism; insulin mimic, synthesizes redox proteins, levels correlate with adipose tissue
is a transcriptional target of CLOCK:BMAL1.
SIRT1
regulates insulin sensitivity
suppresses CLOCK:BMAL1 transcription
Adenosine monophosphate-activated protein kinase (AMPK)
increases cellular energy uptake in response to energy use
directly regulates the clock by phosphorylating CRY1
Without an SCN to provide input, peripheral cells gradually fall out of phase with each other.
There are two striking exceptions to this:
- Scheduled, restricted feeding
- Chronic administration of methamphetamine
Both are capable of organizing circadian outputs in the absence of the SCN.
Food Entrainable Oscillator (FEO)
SCN lesioned animals can still entrain to timed food restriction (TFR).
Interestingly, the FEO does not seem to require a functional molecular clock (Bmal-/- and Per1/Per2-/- can entrain to TFR).
Controls peripheral clocks and body temperature
Food entrainable oscillator is set by feeding, NOT SCN
Food Anticipatory Activity (FAA)
Food anticipatory activity (increases in activity) is observed prior to short meals presented at a scheduled time of day
FAA Persists Following Multiple Brain Lesions
Lesioning of Hippocampus,
Hypothalamus (including SCN)
Cortex, And others…
….does not affect FAA
Leptin – A Satiety Signal
Leptin is a negative regulator of hunger
High leptin = less hunger*
Normally peaks at night
Increases with adipose tissue
levels and insulin levels
Leptin resistance —> obesity
“Outputs” (e.g., behavior or temperature) become “inputs” for other oscillators.
Reciprocal connections exist between the circadian and metabolic system.
Circadian mutants (or disregulated circadian systems) have metabolic problems, and nutrient intake can influence circadian rhythms.
Three determinants of sleep
- Sleep homeostasis
– The longer since you’ve slept the easier sleep
comes - Circadian rhythms
- Social Timing
Sleep
– Universal among higher vertebrates –Sleep deprivation, devastating – One-third of lives in sleep state – Defined: “Sleep is a readily reversible state of reduced responsiveness to, and interaction with, the environment.”
STAGES OF NON-REM SLEEP
Stage 1 – Beginning of sleep cycle – light sleep lasting about 5-10 minutes.
Stage 2 – Bursts of rapid, rhythmic brain activity. Body temperature starts to decrease and heart slows.
Stage 3 – Deep, slow brain waves begin to emerge. Transition between light and very deep sleep.
Stage 4 – Slow wave or Delta Sleep. Deep sleep lasting ~ 30 minutes. EEG shows synchronized delta waves
PARADOXICAL or REM SLEEP
About every 90-120 minutes there is a shift to desynchronized sleep in which thalamic neurons return to
tonic mode.
EEG is dominated by low-voltage, high frequency activity that is similar to the activity seen in waking state.
Individual is very hard to wake up during this stage – paradoxical sleep
Abolition of muscle tone
Although muscle tone is inhibited, eye movement breaks through and there is rapid movement of the eyes (REM)
Transmission of impulses over sensory pathways is greatly decreased
Blood pressure rises a little
Heart rate and breathing become erratic
Hypothalamic regulation of body temperature is lost
Period when dreams occur
Large areas of cortex are active. Sensory input is blocked, therefore no motor activity
• Sleep-Promoting Factors
– Muramyl dipeptide: isolated from the CSF of sleepdeprived
goats, facilitates non-REM sleep
– Interleukin-1: Synthesized in brain (glia,
macrophages), stimulates immune system
– Adenosine: Sleep promoting factor; released by
neurons; may have inhibitory effects of diffuse
modulatory systems
– Melatonin: Produced by pineal gland, released at
night-inhibited during the day (circadian regulation);
initiates and maintain sleep; treat symptoms of jet lag
and insomnia
Sleep Disorders
• Insomnia
– Disorder in going to sleep or staying asleep
• Narcolepsy
– Sleep intrudes into waking period
• Sleep apnea
– Intermittent cessation of breathing
• Motor Disturbances – Sleep walking – Sleep talking – Tooth grinding – Night terrors
NARCOLEPSY
Sudden onset of sleep including REM sleep
Can include REM “fragments” during awake state
– Hypnogogic hallucinations (wakeful dreaming)
– Muscle atonia (cataplexy)
Effects 2-5 / 10,000
– Associated with loss of orexin or receptors
– Orexin is neuropeptide found in hypothalamus that is critical for arousal
Light at Night (LAN)
Drama-c changes in our temporal life since ar-ficial
light was invented over 130 years ago.
• Widespread adop-on of this technology occurred
BEFORE much was known about the importance of
biological clocks orchestra-ng homeostasis.
• Although, ar-ficial light brought great economic
prosperity and changed human life styles, the results
of several experiments show that excessive exposure
to light at night (LAN) reduces the secre-on of the
pineal hormone melatonin (MLT), the physiological
signal of dark.
Excessive exposure to light at night (LAN) reduces the secre-on of the
pineal hormone melatonin (MLT), the physiological
signal of dark.
BMI is Positively Associated With Moderate/Severe Depression
Dim LAN Increases Body Mass and Adiposisty
LAN Impairs Glucose Processing
Timing of Food Intake in Mice Exposed to
Bright and Dim LAN Differed
