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In the NFL, who usually wins more games - East or West Coast teams? Why?
West coast teams. Athletic performance is probably better in afternoon than in the evening
Ultradian Rhythm & examples
- Less than 1 day!
- Repeat themselves frequently
- REM sleep ~every 90 mins
- BRAC = Basic rest activity cycle
Infradian Rhythm & examples
- Longer than 1 day
- Estrous in rodents/Menstrual cycle in humans ~every 28 days
Circannual Rhythm & examples
- Yearly basis
- SAD = Seasonal Affective Disorder. Depression in winter, not so much in SD where lots of sun year round
- Hibernation - Squirrel body weight
What does this picture about E.Coli & mice mortality rates tell us?
That what matters is not just WHAT but WHEN
If give injection in middle of night, 10-15% die
If give injection 4:00 in afternoon, ~90% die!
- MELATONIN IS A HORMONE OF DARKNESS Always high in the night phase
- Released by pineal gland
- Influences circadian & circannual rhythms
- Everyones melatonin rhythm similar, no matter if your nocturnal or diurnal animal
- Small to non in day, great increase at night
Shown it can bifurcate also in Siberian Hamsters!
SCN Suprachiasmatic Nucleus
- "Supra" (above) optic chiasm
- Part of hypothalamus, biological clock depends on
- Main control of circadiam rhythm for sleep & body temp
- Single, isolated cells from SCN maintain circadian rhythm (adjacent cells sharpen accuracy)
- When transplanted other-rhythm SCN tissue, new SCN will adopt the other rhythm
The worst time to drive a car is ___________ .
The best time to go to the dentist is in the __________ .
Morning (If you go in the afternoon....tooth-hurty)
How light resets the SCN
- Small branch of the optic nerve, the retinohypothalamic path, extends directly from the retina to the SCN
- Melanopsin= special population of retinal ganglion cells that have their own photopigment. They receive input from rods & cones & even respond to light when they don't
- Respond to average intensity, slowly
True or False: In Blind mole rats, even though bright light evokes no response or measurable changes in brain activity, light resets their circadian rhythm.
- (Most of the input to that path doesn't come from normal retinal receptors)
If light regulates the CSN, then what happens to blind people?
- Some set their circadian rythms by noise, temperature, meals activity
- Others produce rhythms a little LONGER than 24 hour cycles. This eventually gets out of sync & may lead to sleep issues
True or False: With more sleep deprivation, there is a nice line showing a negative correlation between cognitive performance.
- (The downward trend is actually an undulating pattern, revealing the ebbs and flows of wakefulness throughout the day & the circadian rhythm)
This Actogram shows:
- Free Running Period (FRP tau), double plotted
- Extra credit: Hamster wheel running rhythm in DD (constant darkness)
- Proof of internal/endogenous self-sustaining oscillator/bio clock.
- Circadian rhythm thats MORE than 24 hours
Name some things the biological clock regulates:
- internal temperature
- pain tolerance/sensitivity
This Actogram shows:
- (and the slow process of adjusting to it)
Describe the DeMarain Experiment and how he announced biological clocks/rhythms in plants
- Opening & closing leaves at diff times of day
- Brought into cellar – darkness
- Still opened leaves when light OUTSIDE & close when dark OUTSIDE
- Saw that rhythm persisted
- Someone else looked closer & controlled for temp, other things
How were Aschoff bunkers used in studying biological clocks in humans?
- Got volunteers, Germany, underground bunkers & paid ppl to live in them
- No human contact, no TV, internet
- Got them to remove themselves from sense of time
- Found that they also expressed sleep/wake rhythms & ppl were on LONGER ~25 hr schedule
- Must be coming from WITHIN (same thing found as plants)
- ABOUT 24 hours “CIRCA DIA” = About a day
- Special population of retinal ganglion cells that have their own
- photopigment. They receive input from rods & cones & even
- respond to light when they don'tRespond to average intensity, slowly
- Light -> SCN
Transcription Translation Feedback Loop (TTFL)
- Components are "Clock genes"
- per1 = period 1, per2 = period 2, tim = timeless
- Per1 is transcribed – make mRNA – make protein per1 – gene turned on – protein moves in cell – outside nucleus – reacts to another gene product in cell – forms dimers – goes back in to nucleus – SHUTS OFF per1 gene – not being turned on – no more per1 make – degrades – loses inhibition – per1 transcribed again
- THIS CYCLE TAKES ~ 24 HRS
The Hour-Glass Theory (& evidence against it)
- Idea that we wear down after the day, just to "reset" later
- 3 all-nighters in a row
- Found blips upward in cognition, when body signals it's time to be awake
- nerves in brain cross
- nucleus above
- most important for the clock
ipRGC = Intrinsically photosensitive retinal ganglion cells
- Can respond to light without rods & cells Contains melanopsin: Photopigment that makes these cells light sensitive
- People with lots of this more sensitive to SAD
The syndrome where people go to bed & wake up super early is called __________________
- ASPS = Advanced Sleep Phase Syndrome
- (Genetic component - runs in families)
The syndrome where people go to bed & wake up super late is called __________________
DSPS = Delayed Sleep Phase Syndrome
Clock gene mutants: Tau mutation
- Wild-type2 normal copies~24.1 hours
- Heterozygote1 normal1 mutant~22 hours
- Homozygote2 mutant~20 hours
Explain the Richter studies lesioning the SCN
- SCN-X where SCN surgically removed
- Still did all same behaviors, but no regard to the time of day- no structure
- Completely Arhythmic
In SCN-X rats (SCN removed), who were arhythmic, what drug was given & discovered to induce rhythm again?
What is the pattern of the biological clock in constant darkness (DD)?
What is it called when light causes a wheel-running pattern to form at the same time every day?
What can we conclude by the result of drugs causing a rhythm again after the SCN is lesioned or removed?
That there are clocks OUTSIDE of the SCN
What happened in the LDLD experiments with rodents? How did they go from not bifurcating to bifurcation?
- Turning off lights when sleeping & adding dark period in the day didn't do anything.
- Instead of total pitch dark added tiny amount of light (starlight simulation).
- NOW active in each dark period, 2x/day = BIFURCATED.
- Melatonin was also bifurcated. During darkness, melatonin high. Caused clock to be BIMODAL.
Why are bifurcated animals not affected by jetlag?
Because half of their clock is already there! If they need to adjust to 1 night time, there's much more time to catch up to. If sleep is bimodal, there's not much adjustment needed.
Describe patterns of REM & NREM sleep over time.
- REM: Infants get ~8 hrs then rapidly drops off after 1 year to ~4, then 2
- NREM: 8 as infant, 9 as child, then rapidly declines in to adolescents and slowly declines into adulthood.
What is the pattern of infant sleep in first yr of life?
- Newbord: Sporadic. No rhythm.
- At ~4 mos: Sleep mostly at night, awake in day.
What is a Chronotype & what does it look like for the population?
It's a "time type" of either Larks (early bird) or Night owls.
- Looks like a normal distribution, with majority of people somewhere in the middle.
What are the sleep trends across gender?
- Females go through puberty earlier, so start going to bed late earlier in life.
- Males still go to bed later after hitting puberty.
College students average ________ hours of sleep
Two-Process Model of Sleep
- Process S = Sleep debt.
- Homeostatic process. Wake up in AM - feel refreshed - Process builds over day - get more tired - accumulates over time.
- Process C = Circadian.
- Daily clock. Programmed to be less efficient at certain times of the day. Ups & downs in the day.
- Interaction b/w them:
- The greater distance, the more likely sleep is needed/will come. Circadian wakes you up at the smallest distance
Explain the Two-Process Model of Sleep graph when sleep is deprived
- S goes UP & UP
- Accumulates additional sleep debt during times where there would normally be sleep.
- C does same pattern - in waves
- So person experiences lows & highs, still with cognitive impairment
- When finally does sleep - sleeps longer to remove debt
- Rebound = Sleeping more to make up additional debt
- Higher TST = Total Sleep Time
What happened to rats when sleep deprived?
- Lost weight, metabolism changed, ulcers.
- They died within 11 - 32 days =(
Some symptoms of sleep deprivation in humans (THERE'S MANY!):
- Cognitive impairment
- Memory lapses or loss
- Impaired moral judgement
- Symptoms similar to ADHD
- Immune system
- impaired – easier to become sick
- Risk of Type 2 diabetes – wt gain
- Growth is suppressed – phsychological dwarfism
- Risk of obesity
- Decreased body temp
- Increased risk of heart disease
What happened in the sleep studies with humans in bed for 8, 6 & 4 hours?
- Even if in bed for 8 hours - they're not actually sleeping that long (6.5 hrs of sleep). So they had cognitive impairments.
- 6 hrs in bed = 5.5 actual sleep
- 4 hrs in bed = 3.5 actual sleep
- People in the 4 & 6 hr group UNABLE TO TELL HOW BAD THEY DID! Not sensitive to effects.
Alpha , Beta, Delta waves
- Alpha = Small/spiky. Lots of neurons doing lots of things. Relaxed Arousal (8-12 Hz). Baseline activity.
- Beta = Attentive Arousal (13 - 30Hz)
- Delta = Large and slow. Bunch of neurons in sync to do this pattern.
Sleep Spindles & K Complexes:
- Occur in Stage 2 of sleep.
- Sleep spindle – hippocampus. Transient bursts. Related to IQ & learning
- K complexes – responding to sound
- Studies count sleep spindles & k complexes & relate to how well ppl learn & consolidate memories
1. Light. 4-5%. Muscle activity slows. Twitching. Theta activity
2. Breathing & heart rate slow. 45-55%. Sleep spindles, K complexes.
3. Deep. 4-6%. Beginning of Delta waves.
4. Deepest. 12-15%. Delta waves >50%. Rhythmic breathing, limited muscle activity.
- 5. REM. 20 - 25%. Close to light (stage 1) sleep in brain, but muscles relaxed close to deep (stage 4). Occurs every 90 mins. Eyes dart around. REM increases in amount of time, the closer to waking up you get.
- Atonia = Lack of muscle control
Why do the eyes dart around during REM?
- To get sufficient oxygen to the corneas! They get oxygen directly from the surrounding air. They deteriorate in sleep. While they do get some oxygen from the fluid behind them, it becomes stagnant so moving them increases oxygen supply.
- Makes sense b/c it happens at end of sleep cycle when fluid builds up. Other manifestations of REM may be byproduct of the eye movements. Also if you sleep longer you devote more time to REM.
- However, medications that restrict REM sleep arent shown to affect peoples corneas.
What are some general trends in the sleep cycle pattern?
- Each ~ 90 mins. Beginning cycles you get more deep sleep, in stages 4. That decreases throughout the night to only get to stage 3, as the REM stage increases.
- = Slow Wave Sleep
- Stages 3 & 4
- Delta waves
Muscle "paralysis" during sleep. Usually happens in REM.
Types of Insomnia:
- Onset = Could be Circadian rhythm disorder
- Maintenance = Anxiety #1 related
- Terminal = Up too early. Circadian disorder.
- Chronic = Leads to many cognitive & emotional impairments
- Fatal Familial = Deadly. Genetic. Due to prion mutation. Die within 18 months.
Causes of Narcolepsy:
- Orexin/Hypocretin - NT
- Lack hypothalamic cells that produce & release orexin.
- Possibly autoimmune reaction - body attacks them?
- Dogs lack gene for orexin receptors have narcolepsy.
- In humans: Found that receptors were fine, just less to act on receptors. In spine: Normal levels. In brain: none.
- Continuous Positive Airway Pressure
- Used to treat sleep apnea. Keeps airways open so ppl don't stop breathing in sleep.
Structures found to be important during sleep:
- Basal forebrain
- Limbic system
Reticular Formation & Sleep:
- Mid/Hind brain structure
- Motor control
- "Reticular" = net. neural connections.
- Release of AcH (Acetylcholine)- excites cells in the hypothalamus, thalamus, basal forebrain
- High during REM (wakefullness), LOW in NREM
Locus Cereleus & Sleep:
- Waking activated by norepinephrine
- Activity high during wake
- Low in REM - suppresses REM sleep
- Bursts during emotional arousal
- Storage of recent memories & increases wakefulness, when stimulated
- (5-HT & Seretonin also low in REM)
True or False: Sleep & hibernation are the same thing.
- (Squirrels de-hybernate to sleep)
Basal Forebrain & Sleep
- Release Excitatory NT(AcH) - Excites thalamus & cortex for learning, attention, shifts in sleep stages
- Releases Inhibitory NT (GABA) - inhibiting thalamus & cortex
Definition of Learning:
Change in behavior that results from experience
Definition of Memory:
Retention of changes over time separate from development
Name the 2 types of Declarative memory & what they are involved in:
- 1. Semantic = Facts
- 2. Episodic = Autobiographical. Stuff that happened to you.
Name the 4 types of Non-Declarative memory & what they are involved in:
- 1. Procedural/Skill = Cerebellum, motor cortex, basal ganglia. Include practice; sports, playing instrument, riding bike.
- 2. Associative = Classical Conditioning. Cerebellum. ex Pavlov's Dogs. Fear Memory = Amygdala. Pairing tone w/shock.
- 3. Non-Associative = Habituation (repeated stim, LESS sensitive). Sensitization (repeated stim, MORE sensitive).
- 4. Priming = Using stimulus to affect later behavior.
Describe case study HM (Henry Molaison)
- Most studied human amnesia case
- Seizures at 16 - Removed parts of medial temporal, hippo, amygdala
- He suffered BOTH Anterograde & Retrograde amnesia
- He never recalled meeting the people studying him. Would have to be introduced every time
- Could learn certain TYPES of memories:
- Mirror writing task – Look into mirror next to paper
- Write name so it looks correct in mirror. Very hard to do b/c we usually look at paper – must retrain brain
- Interesting: He got very good at it, but never remembered practicing/training on it
FUTURE: Inability to form NEW memories
- Loss of memories from the past
- Going backwards
- OFTEN GRATED
- – WORSE in more recent past, early past is better
- OR COMPLETE
- – can't remember ANYTHING from past
HM's most intact memory was for the DISTANT past – Implies:
Those memories are stored OUTSIDE the medial temporal lobe (which is largely what he had removed)
Clive Waring & Memory Loss
- British music composer
- Herpes encephalitis infection in 1985 left him with Anterograde & Retrograde Amnesia
- Remembers his wife, even though they were only married 1 yr before the infection
- Writes in journal all the time: "Waking up for the FIRST TIME" with all the other entries crossed out
- He knows facts about the world but most past memories wiped out - except for maybe emotional ones.
Jill Price (AJ) & unusual memory experience:
- Hyperthymestic Syndrome = Unusual autobiographical memory
- "The Woman Who Can't Forget"
- Remembers entire timeline, including what she ate on a given day
- Not good at school, face memory, facts, executive functioning
- Lacks ability to switch memories off
- Caused by Thiamine deficiency
- Degeneration of mammillary bodies
- Linked to Alcohol syndrome (poor diets may lead to thiamine deficiency)
- Both types of amnesia
- Confabulation = They add completely new & unecessary or irrelevant parts of stories & situations that are unture
Alzheimers & memory: Early & late symptoms, risk & protective factors
- 60 - 80% of dementia
- Early: Difficulty remembering names/events
- Late: Impaired judgment, disorientation, confusion, difficulty speaking, swallowing, walking
- Risk factors: Age #1, Female more likely, family history, mild cognitive impairment, head trauma earlier in life, genes
- Protective factors: Active mind, social engagement, healthy heart & lifestyle, low cholesterol/ non-smoking
Alzheimers & memory: What's going on in the brain? What are the treatments?
- Usually not diagnosed until AFTER DEATH
- 1. Cell death - Brain is usually smaller.
- 2. Amyloid Plaques - Deposits in cell & tau proteins inside the cells accumulate. Forms Tangles. Found in cortex, hippocampus, basal forebrain, decrease in AcH
- Approved Drugs: Cholinestarase which prevent breakdown of AcH. Memantine - NMDA-Receptor antagonist.
- Non Approved Drugs: Insulin - Disregulate feeding/body cycle via intranasal spray (to prevent going into blood stream)
The remembering curve over 0 second & 30 second delay shows:
- Recall after 0 delay is best for first and most recent events.
- Recall after 30 second delay is best for first ONLY.
- First get list - start consolidating words first. This becomes difficult the more you get. Tested immediately - Words still stored in short term.
- Tested later - Later words lost, first get stored in Consolidation.
Visual Learning Task + Sleep
- Difficult task of picking out symbols.
- Measure if ppl get more or less sensitive over time
- People given 12-hr delay with & without sleep
- People WITH SLEEP in between training & trails did SIGNIFICANTLY better at retest.
2 Main areas involved in the Eyeblink Reponse:
- 1. Lateral Interpositus (Nucleus of the Cerebellum)
- 2. Red Nucleus
What happens to eyeblink responses after the LIP & Red Nucleus recover function? What do these findings say about their functions?
- LIP - At first suppressed still - then takes 3-4 sessions to max out.
- RN - On first session already at 80%
- *This says that LIP involved in learning, & RN involved in expression of learned trait
What is eyeblink classified under in the Learning & Memory model?
Associative memory - Classical conditioning