Circadian Rhythms and TTX Effects on SCN Neurons
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Questions and Answers

What is the effect of tetrodotoxin (TTX) on isolated SCN neurons?

  • It stops their firing activity. (correct)
  • It alters their recovery rhythm.
  • It enhances their rhythmic firing.
  • It synchronizes their firing activity.

What happens to the recovered rhythm of SCN neurons after the washout of TTX?

  • It becomes out of sync with the pretreatment rhythm.
  • It remains completely unchanged.
  • It is in phase with the pretreatment rhythm. (correct)
  • It exhibits increased variability in firing patterns.

Which statement is true regarding the activity of individual SCN neurons?

  • They are all inactive at the same phase.
  • They are active at different phases but can couple in networks. (correct)
  • All individual neurons fire synchronously.
  • They have identical firing patterns throughout the day.

What does the presence of heterogeneous cell types within the SCN suggest?

<p>The SCN functions as a multi-oscillator system. (A)</p> Signup and view all the answers

What type of recordings can provide evidence for electrical activity in SCN subpopulations?

<p>Single cell recordings. (C)</p> Signup and view all the answers

What effect does simulation of a short photoperiod have on the population locomotor pattern?

<p>It leads to a narrow population pattern with high amplitude rhythm. (C)</p> Signup and view all the answers

How does the population's rhythm amplitude change with longer photoperiods?

<p>Rhythm amplitude remains unchanged but has a broader peak. (D)</p> Signup and view all the answers

What is the interpretation regarding the circadian FRP and amplitude of individual neurons during long days?

<p>FRP remains unchanged while amplitude decreases. (A)</p> Signup and view all the answers

What property is suggested to encode seasonal changes in the circadian system?

<p>Network property of coupling between neurons. (A)</p> Signup and view all the answers

What change occurs in the coupling between neurons due to different photoperiods?

<p>It varies, affecting network properties during different lengths of days. (C)</p> Signup and view all the answers

What effect does a 1-hour light pulse have on hamsters?

<p>It induces a phase shift of several hours. (A)</p> Signup and view all the answers

What is the result of novelty-induced wheel running in hamsters?

<p>Significant phase shift in their circadian rhythm. (B)</p> Signup and view all the answers

How does the human exercise paradigm relate to phase shifts in circadian rhythms?

<p>Exercise performed at different clock times causes varying phase shifts. (B)</p> Signup and view all the answers

What is the consequence of long-term exposure to constant light (LL) in hamsters?

<p>Behavioral and metabolic effects are observed along with alterations in the SCN. (C)</p> Signup and view all the answers

What happens when a group of hamsters is transitioned from light/dark (LD) to constant light (LL) conditions?

<p>They exhibit significant changes in their normal activity patterns. (B)</p> Signup and view all the answers

What is observed in VIP-knockout mice regarding photoperiod memory?

<p>There is no memory of photoperiod duration after release from LD to DD. (B)</p> Signup and view all the answers

How does the amplitude of SCN rhythms compare between young and old animals?

<p>Young animals show a higher amplitude rhythm than old animals. (A)</p> Signup and view all the answers

What characteristic is common in the SCN of older animals?

<p>SCN cells may be out of sync and sometimes in antiphase. (D)</p> Signup and view all the answers

What potential non-drug approaches could help restore rhythms in the elderly?

<p>Enforced light/dark cycles or exercise/activity. (B)</p> Signup and view all the answers

How is running wheel activity perceived among wild mice?

<p>They spontaneously enjoy playing on running wheels. (C)</p> Signup and view all the answers

Which region of the SCN primarily receives major afferents from the eyes?

<p>Core region (B)</p> Signup and view all the answers

Which neurotransmitter predominates in SCN neurons across both the core and shell regions?

<p>GABA (B)</p> Signup and view all the answers

In terms of neuronal composition, which type of neurons predominates in the shell region of the SCN?

<p>AVP neurons (D)</p> Signup and view all the answers

What is the role of VIP in relation to the SCN?

<p>It is involved in gating/photic induction. (C)</p> Signup and view all the answers

Which factor distinguishes the core and shell regions' functions in terms of circadian rhythms?

<p>Core neurons are involved in autonomous per mRNA rhythms. (B)</p> Signup and view all the answers

What characterizes the functional composition of the SCN?

<p>Almost all neurons are GABAergic. (A)</p> Signup and view all the answers

Which peptide is commonly associated with the SCN's circadian rhythms?

<p>Vasoactive intestinal peptide (VIP) (B)</p> Signup and view all the answers

Which statement best describes the spatial differences in the SCN?

<p>Different regions have different roles in circadian versus photic rhythms. (A)</p> Signup and view all the answers

What is the primary effect of long-term exposure to LL on the SCN?

<p>It affects behavior and metabolism. (A)</p> Signup and view all the answers

In which type of animals is SCN activity and locomotor activity positively correlated?

<p>Diurnal animals. (A)</p> Signup and view all the answers

What role does electrical activity in the SCN have according to the content?

<p>It enhances neuron amplitude. (D)</p> Signup and view all the answers

What is the relationship between SCN activity and locomotor activity in nocturnal animals?

<p>They are inversely correlated. (A)</p> Signup and view all the answers

What does proper phasing of activity do to SCN rhythms?

<p>It enhances the amplitude of SCN rhythms. (A)</p> Signup and view all the answers

Which statement about the multi-oscillator structure of the SCN is true?

<p>It contributes to precision and robustness. (D)</p> Signup and view all the answers

Which environmental factors can influence SCN behavior?

<p>Photoperiod and temperature cycle. (D)</p> Signup and view all the answers

What can enhance SCN amplitude and cause phase shifts?

<p>Activity and exercise. (D)</p> Signup and view all the answers

Flashcards

SCN neuron firing

Individual SCN neurons can fire independently with different rhythms.

SCN synchronization

Neurons in the SCN are connected and communicate to synchronize the rhythms.

TTX effect on SCN

TTX temporarily stops firing activity, but the rhythm resumes in phase with the previous rhythm after TTX washout.

Multi-oscillator system

The SCN contains many interacting oscillators that coordinate their rhythms to generate a synchronized output.

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Heterogenous cell types in SCN

The SCN comprises many diverse types of cells.

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SCN Regions

The suprachiasmatic nucleus (SCN) is comprised of at least two functionally distinct regions: core and shell.

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Core SCN function

The core SCN receives input from the eyes and plays a role in photic induction and gating.

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Shell SCN function

The shell SCN projects efferent outputs and has autonomous rhythms.

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GABAergic SCN neurons

More than 90% of SCN neurons are GABAergic, meaning they use GABA as a neurotransmitter.

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AVP neurons

Arginine vasopressin (AVP) neurons are predominantly found in the shell SCN.

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VIP/GRP neurons

Vasoactive intestinal peptide (VIP) and Gastrin-releasing peptide (GRP) neurons are predominant in the core.

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Efferent Outputs

Signals, often outputs, sent away from the SCN area.

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Afferent Inputs

Signals received by the SCN, often from the eyes.

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Photoperiod effect on SCN

The length of the day (photoperiod) changes the rhythm of the SCN, causing different patterns of neuron firing.

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Short photoperiod effect on SCN

Short days (e.g., winter) cause the SCN to have a narrower peak rhythm with high amplitude.

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Long photoperiod effect on SCN

Longer days (e.g., summer) cause the SCN to have a broader, less strong peak rhythm.

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Seasonal encoding in SCN

The SCN changes its rhythm based on the length of the day. This allows animals to adapt to seasonal changes.

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Network property of SCN

The rhythm of the SCN isn't just from individual neurons, it's a result of how the neurons are connected and interact.

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VIP-knockout mice

Mice genetically modified to lack the VIP gene, resulting in a disruption of circadian rhythms.

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Synchronization in the SCN

The process by which individual neurons within the SCN coordinate their activity to generate a single, synchronized rhythm.

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Aging and SCN Rhythm Amplitude

The amplitude (strength) of the SCN rhythm decreases with age, suggesting a decline in network function.

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Restoring Rhythm Function

Potentially improving circadian rhythms in the elderly by strengthening SCN network communication through exercise or light-dark cycles.

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Running Wheel Activity

Running wheel activity in mice is a natural behavior, not a symptom of captivity.

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Activity-induced Phase Shifting

Changes in the timing of the circadian rhythm caused by physical activity or novelty. This demonstrates that the body's internal clock can be influenced by external factors.

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SCN feedback mechanism

The concept that activity-induced changes in the circadian rhythm send feedback signals back to the suprachiasmatic nucleus (SCN), the brain's master clock.

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Human Exercise PRC

The phase response curve (PRC) for exercise in humans. It shows how the timing of exercise affects the shift in the circadian rhythm.

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Effects of LL Exposure

Prolonged exposure to constant light (LL) disrupts normal circadian rhythms, affecting behavior, metabolism, and the function of the SCN.

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SCN's Adaptive Role

The SCN dynamically adapts to environmental changes, particularly photoperiod (day length), by altering its rhythmic activity to synchronize with the environment.

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SCN and LL Exposure

Long-term exposure to constant light (LL) changes the SCN's activity and how animals behave and use energy (metabolism).

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Activity and SCN in Day-Active Animals

In animals that are active during the day, the peak in their SCN activity and their peak in physical activity tend to line up.

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What does MUA stand for?

MUA stands for multi-unit activity. This term is related to the electrical activity of the SCN.

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SCN Feedback Flow

The SCN functions in a complex feedback loop. Everything from genes to behavior influences the electrical activity of the SCN.

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SCN Output and Nocturnal Animals

In nocturnal animals, the SCN's activity and the animal's physical activity follow opposite patterns. When the SCN is most active, the animal is typically at rest.

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Enhance SCN Rhythms

Regular activity and behavior can make the SCN's rhythms stronger. It's like giving the rhythm a boost.

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Multi-Oscillator SCN

The SCN is made up of many individual oscillators that work together. This allows for precision, stability, and the ability to respond to seasonal changes.

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SCN's Role in Seasonal Changes

The SCN can change its rhythm depending on the length of day and night (photoperiod). This helps animals adapt to seasonal changes.

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Study Notes

BSci 3230 Study Notes

  • These files are for BSci 3230 student use only for exam preparation
  • Material may be copyrighted and sharing is not permitted.
  • Using the files for purposes other than studying for BSci 3230 is prohibited.

Circadian Rhythms

  • Feedback at every step in SCN activity, with behavior modulating SCN amplitude
  • Nocturnal rodent SCN activity and locomotion are inversely correlated
  • Aging and exercise have opposite effects on the SCN clock

Feedback Control

  • Genes directly affect membrane potential needed for rhythms
  • Ion channel activity enhances SCN neuron amplitude
  • Activity/exercise can increase SCN amplitude and shift phases.
  • Entrainment and seasons affect the environment (e.g., light, photoperiod, temperature cycles)

Circadian Behavior: Cell-Based or Network Dependent?

  • Single dissociated SCN neurons are rhythmic in vitro
  • Isolated SCN neurons on a multielectrode plate (MEP) exhibit rhythmic firing
  • Is the rhythm from the SCN based on oscillators' coupled cell-autonomous coupling or a non-oscillating network?

SCN Structure

  • Human SCN is composed of ~40,000 neurons of diverse types
  • Mice and primates both have SCNs localized in the hypothalamus

Multi-Oscillator System in the SCN

  • Individual SCN neurons are active at different phases, connected by networks.
  • Per-luc molecular rhythms within the SCN
  • Electrical activity within subpopulations
  • Yamaguchi et al. (2003) research shows coupled neuronal networks provide overall synchronization
  • Schaap et al. (2003) studies support multiple distinct oscillators
  • SCN is comprised of at least two regions and the core and shell have differential mechanisms.

SCN Core and Shell

  • Core receives major afferents from eyes primarily through VIP/GRP neurons
  • Core neurons are GABAergic, and are responsible for Gating/photic induction
  • Shell projects outputs predominantly made up of AVP neurons for autonomous Per mRNA rhythmic regulation
  • The shell is also GABAergic

Spatial Differences in Circadian vs Light-Induced Expression

  • CT4 no light vs CT16 light: SCN neuronal activity differences
  • Different SCN neuronal expression patterns during light/dark cycles
  • The data from (Shigeyoshi et al. 1997) is confirmed

Left/Right SCN Coupling

  • Left/right SCN neurons are usually coupled.
  • Uncoupling can occur during "splitting" in constant light
  • The research (de la Iglesia et al., 2000) confirms this

SCN Networks

  • Clocks within cells composed of multiple interlocked feedback loops
  • Core neurons responsible for photic induction and interface with environment
  • Shell neurons are autonomous rhythmic and have additional coupling
  • Left-right SCN has additional coupling
  • A variety of neurotransmitters and signaling molecules are involved and important in core functions like glutamatergic (Glu), VIP, PACAP, GABA, and various others.

Functional Relevance of the Multi-Oscillator Structure

  • Precision, robustness, and resilience benefits from multiple coupled oscillators.
  • Adaptation to photoperiods is mediated by phase differences among SCN neurons.
  • Seasonal encoding is a network property

Beyond the Single Neuron

  • In the intact animal, period measurements, for wheel running correlates to the circadian cycle
  • SCN slice measurements show similar periods
  • Measurements with isolated neurons also correlate
  • Accurate clock function relates to precise SCN structure

Mouse mPer2:luc Cultures

  • Proportion of rhythmic vs arhythmic neurons varies with density
  • Lower density cultures demonstrate a higher percentage of cells exhibiting rhythmic activity compared to high-density cultures which have a greater percentage of cells without a rhythm.

Functional Relevance of the Multi-Oscillator Structure

  • Adaptation to photoperiods: differing phases among SCN neurons contribute to photoperiod adaptation.
  • Phase differences between neurons support photoperiod adaptation
  • Short and long photoperiodic periods cause different patterns in neural activity and amplitude
  • Seasonal encoding is a network property

Long-Term Exposure to LL

  • Effects on behavior/metabolism and the SCN are demonstrated by changes over weeks
  • Long-term LL exposure affects various parameters like weight, glucose levels, and also electrical rhythms in the SCN.
  • The SCN and behavior are affected in long-term conditions

Day-Active vs. Night-Active Animals

  • Regardless of locomotor phasing, the SCN metabolism and activity peaks during the day.
  • Day-active animals have similar SCN phasing and functionality to nocturnal animals

Activity-Induced Phase Shifting

  • Hamsters placed in new running wheels shows a transient phase shift
  • Exercise can affect SCN rhythm, and possibly enhance phase shift
  • Novelty and induced wheel running activity can cause phase shifts in hamsters

Further Studies

  • Potential human applications using L/D cycles in ICU, neonatal care, etc., could potentially enhance rhythm.
  • Exercise and aging have opposite effects on the SCN.

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This quiz explores the influence of tetrodotoxin on the electrical activity of suprachiasmatic nucleus (SCN) neurons. It examines how changes in photoperiod affect circadian rhythms and the implications of neuronal coupling variability within the SCN.

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