Biopsych 2nd test

circadian rhythm

-Regulate different types of pathways and systems by regulating when they are most active and least active
-Heart rate, blood pressure, body temperature cycle throughout the day

Melatonin

-enables body to relax, lowers body temperature, lowers blood pressure
-----Allows natural onset of sleep to happen
-----Doesn't cause sleep itself

Chronotype

a person's disposition to be a "morning person" or an "evening person"

suprachiasmatic nucleus

Biological clock
-Located in midbrain - diencephalon
-telencephalon/cerebral cortex
-Reacts to levels and changes in light
-----Light stimulates the SCN and results in decreased melatonin production by pineal gland in the morning
-----Low light (darkness) - leads to increased melatonin production

Melatonin (specifics)

-derivative of serotonin
-Decreases blood pressure, decrease core body temperature, increase relaxation

melanopsin

-More receptive to blue light waves
-----Less blue light before bed to allow release of melatonin
-----Blue light causes more activity in retinal cells

-Stimulates SCN as light is detected
Results in
-----SCN stimulates lateral hypothalamus nuclei to release orexin (Responsible for onset of waking - increase level of alertness)
-----SCN releases GABA (GABA suppresses activity in pineal gland - less melatonin is released)

Orexin

Responsible for onset of waking - increase level of alertness

-From lateral hypothalamus
-Levels high during wakefulness
-Low levels during rest and all sleep stages
-Increase activity in the brainstem and forebrain arousal systems

GABA

-a major inhibitory neurotransmitter
-suppresses activity in pineal gland - less melatonin is released

-From ventrolateral preoptic area (vlPOA)
-Suppress alertness and behavioral arousal, and promote sleep

restorative theory

-Repair and regeneration of body
-Reestablish biological functions
-Muscle repair, tissue growth, protein synthesis, growth hormone release
-Necessary for optimal functioning of physiological systems

When sleep deprived...
-Decreased cognitive function - memory, focus, thinking, thought processes
-Over long periods - increased diseased states

elimination theory

-Rid the brain of excess sensory information
-Certain synaptic connections are strengthened and others are weakened (or not established) during sleep
-Synaptic pruning

synaptic pruning

-Higher rate in children
-Don't stimulate pathways repeatedly, they weaken and connection is broken

Brain Plasticity Theory

-Neural reorganization and growth of brain structures
-Happens more during sleep than waking hours

Infants - sleep about 16 hours a day, 8 hours are REM sleep

Infancy → young childhood: brain growth and neural connections is highest at this point

Immobilization theory (evolutionary theory, adaptive theory, or inactivity theory)

-Sleep is innate response with species specific patterns
-----Each species has particular pattern and cycle of sleep and wake
-----Keeps one inactive and safe during least efficient part of light cycle
---------Biological/genetic response

Energy Conservation Theory

-Following survival activities, periods of inactivity are a good way to conserve energy that we generate from the food we consume
-Hunting and gathering is difficult at night, so we sleep during this time

slow-wave sleep

-deepest, most restorative functions occur
-Seems essential for survival - growth hormone release

-Lack of sleep correlated with various disorders (cardiovascular disease, diabetes, obesity, etc)
-Consolidation of declarative memory (Easily accessible factual memory - what you can easily talk about)

fatal familial insomnia

-Proteins folded in abnormal way that causes fatal changes in nervous systems
-Suffer from insomnia in middle ages
-Cause changes in thalamus
----Inability to stay asleep that leads to trouble falling asleep at all - only given 6 months to a year of life left
-----3-4 months of little to no sleep at all is fatal

REM sleep functions

-Dream stage
-Promote brain development
-----Infants spend 8 hours in _____
-Facilitate learning
-Consolidation of nondeclarative memory
-----Procedural - how to do things
-----Motor skills, tasks, sequencing, executing functions

REM rebound phenomenon

-When able to come off of sleep deprivation, you make up REM sleep first before slow-wave sleep
-After you catch up on REM sleep, you'll catch up on slow-wave sleep afterwards
-REM sleep may be more important than slow-wave sleep since you make up for it first

Electroencephalogram (EEG)

-Electrical potential recorded from macroelectrodes placed on the scalp ("brain waves")
-Gives large number of wave indicators on a read-out that the researcher or physician can look at particular wave patterns to determine if you are asleep/awake and what stage of sleep you're in
-Produced by activity of neurons in telencephalon

Electrooculogram (EOG)

-Measure of eye movements seen during sleep
-Slow wave sleep: slow rolling eye movements
-REM: rapid eye movement (left-right)
-----Muscles around eyes are firing
-----When you come out of REM sleep, eye movements go back to being slow
-Identifies which stage of sleep you're in
-Very few eye movements in early stages of sleep

electromyogram (EMG)

-Electrical potential recorded from an electrode placed on muscle
-Measures changes in muscle tension/activity particularly in facial and neck muscles
-----Mentalis muscle
----------Connects lower lip to chin
----------Immediately weak and loses muscle tone when you fall asleep - sudden change in muscle tone to identify whether you are asleep
-Lose muscle tone as you fall asleep, lose all muscle tone during REM sleep

Pneumotachograph*

A device for continuous recording of a patients respiratory volume and airflow based on the Poiseuille Hagen formula. It is a fixed orifice flow meter.

passive theory of sleep*

sleep occurs when the body and brain fatigue and sensory information becomes diminished

cerveau isole (Bremer (1936))

transection through the midbrain; animal shows constant unresponsiveness and SWS

-"isolated forebrain"
-Separated midbrain from hindbrain
-EEG pattern - slow wave sleep
-----Cats would sleep 24/7
-----Could only wake them up with very strong smell or with a loud noise - pathways from nose and ears were not affected
----------Would wake up for a few seconds and fall asleep again
-Cut off brain from all bodily sensations except for smell and hearing
-By reducing physical and environmental sensations, you allow sleep to come naturally

encephale isole Bremer (1936))*

"isolated brain"
-Separated spinal cord from rest of brain
-Normal patterns of sleep - normal brain waves
-Paralyzed

active theory of sleep*

brain actively puts you to sleep and wakes you up
- bunch of synapses correlated with sleep and wake patterns [neurotransmitter systems

Moruzzi and Magoun (1949)

???

Sleep-wake cycle

a daily, naturally occurring 24-hour circadian rhythm of sleep and wake states regulated by a biological clock

-70-100min to get through first sleep cycle
-----90-120 minutes to complete the next sleep cycles
-If you wake up through the night, you start again at stage 1 sleep
-----The only time you move through stage 1 sleep is if you're starting from waking
-----If you don't wake up throughout the night, you won't experience stage 1 again

non-REM stage 1

-1-7 minutes
-Can easily be woken out of - doesn't feel like you were sleeping

non-REM stage 2

-10-25 minutes
-Gets longer as the night progress
-Makes up about 50% of sleep time
-Harder to be woken up - feels like you were asleep, but not deep sleep
-especially to sound or our name being called

non-REM stage 3/slow wave sleep

-20-40 minutes
-Get shorter as the night progresses
-Last sleep cycle of the night does not go into stage 3 at all

beta waves

-Irregular, low amplitude, high frequency 13-30Hz
-Indicative of being awake
-----Thinking, processing, actively engaging

alpha waves

-Fairly regular, low amplitude, high frequency 8-12Hz
-----Indicative of being awake, but more relaxed
----------Daydreaming, letting your mind wander, meditation, watching TV when you're not focusing/trying to pay attention, zoning out
-----Show as we're getting ready to sleep

theta waves

-Moderate frequency, low amplitude, 3.5-7.5Hz
-Indicative of sleeping
-Stage 1 sleep, continues into stage 2

Sleep spindles

-occurs only in stage 2 sleep
-Short bursts of 12-14Hz
-Mechanisms activated in response to sounds we hear when we're sleeping
-----Dampens sensation of sound to help us stay asleep
-----Has to be perceived as non-threatening

K complexes

-occurs only in stage 2 sleep
-Sudden sharp waveforms
-Activated from touch on skin
-Leg spasms from muscles relaxing, feeling a blanket, someone else touching you
-----Dampens sensation of touch to help you stay asleep
-----Has to be perceived as non-threatening

delta waves

-High amplitude, low frequency, 1-2Hz
-Slow wave sleep - stage 3

Wake up out of this feels:
-Feel groggy - may not be aware of surroundings
-Hard to wake up out of this stage - may have to shake someone or touch them - can call their name to help

REM sleep

-Alpha and theta waves
-Paradoxical - wave pattern indicates that you're asleep and awake at the same time
-Fairly easy to wake up out of REM sleep

Acetylcholine (cholinergic neuron)

-Dorsal pons and basal forebrain
-Plays role in arousal of cerebral cortex
-Levels high during wakefulness and REM sleep
-Project to and impact:
-----Medial pons, thalamus, cortex
-Involved in cortex and hippocampus arousal

Norepinephrine

-Locus coeruleus (in pons)
-Plays role in attention and vigilance
-Possible role in "behavioral" arousal
-Levels high only during wakefulness (lower levels during slow wave sleep and lowest during REM)
-Project to and impact:
-----Cortex, thalamus, hippocampus, cerebellum, pons, and medulla

Serotonin (5-HT) (serotonergic neuron)

-Raphe nuclei - medial pons near caudal end of reticular formation
-Levels high during wakefulness
-Levels fall as descending towards REM sleep
-Cortical and behavioral arousal
-----More activity in cortex with release of serotonin
-----More motor/behavioral activity
-Plays a role in activating behavior (pacing, chewing, grooming in rodents)
-Project to and impact:
-----Thalamus, hypothalamus, cortex, hippocampus, basal ganglia

Histamine

-anti_____________ - may feel tired/dopey after taking
-Tuberomammillary nucleus (in hypothalamus)
-Levels high during wakefulness
-Levels low during slow wave sleep and REM sleep
-Implicated in control of wakefulness and arousal
-Project to and impact:
-----Cortex, thalamus, hypothalamus, basal ganglia, basal forebrain

Adenosine*

-By product of neuron metabolic activity
-----The more active you are physically and mentally will increase your levels
-Peptide released by neurons during high levels of metabolic activity throughout the day
-Increases activity in the vlPOA
-----Receptors for adenosine in this area
----------Stimulated - neurons are depolarized = more activity in vlPOA = more release of GABA = more inhibition on arousal systems

ventrolateral preoptic area

a group of GABAergic neurons in the preoptic area whose activity suppresses alertness and behavioral arousal and promotes sleep

vlPOA

ventrolateral periaqueductal gray*

Dorsal midbrain
Location of REM-OFF

vlPAG

sublaterodorsal nucleus

a region of the dorsal pons, just ventral to the locus coeruleus, that forms the REM-ON portion of the REM sleep flip-flop

SLD

sleep/wake flip flop

-Mutually inhibitory mechanism
-----When one part becomes active, it suppresses activity in the other
-Not an on/off
-----No areas ever shut off, one just operates more or less in comparison to the other
-----scale/seesaw - more pressure on one causes other side to raise, release pressure on one side causes other to fall

When flip-flop is "on"

-Aroused, awake, active
-Excitatory neurotransmitters being released
-GABA is being released onto vlPOA - quiets down area of brain that is thought to promote sleep
-----Helps you stay awake

Maintaining wakefullness

-Orexin comes from lateral hypothalamus - excitatory - depolarize/increase activity in arousal systems
-----Solid line - more activation in arousal - more neurotransmitters being released

When awake
-We can keep firing Orexin thru motivation to remain awake

When flip-flop is "off"

-vlPOA promoting activity - firing GABA onto arousal systems
-More GABA = less GABA onto vlPOA = less arousal neurotransmitters

When awake... (to turn flip-flop "off")

-Adenosine
-----Longer you stay awake with no naps, higher level of adenosine
----------Naps reduce adenosine levels
-----Stimulates activity in vlPOA
----------More activity = more GABA release on arousal systems = reduces release of arousal neurotransmitters
-Caffeine - adenosine receptor blocker

Orexin and vlPOA relationship

-vLPOA will inhibit lateral hypothalamus activity to reduce activity of Orexin
-----Orexin cannot override the arousal system and bring you out of sleep

REM sleep flip-flop

Occurs between vlPAG and SLD - either turns on or shuts off REM

Narcolepsy

A sleep disorder characterized by uncontrollable sleep attacks. The sufferer may lapse directly into REM sleep, often at inopportune times.

symptoms of narcolepsy

-Sleep attack (i.e. strong daytime sleepiness)
-Cataplexy
-Sleep paralysis
-Hallucinations
-Difficulty staying awake
-----Irregulation in sleep-wake cycle
-REM sleep intrudes into waking state
-----Cataplexy and hallucinations
-Skip slow wave sleep - move quickly into REM from waking
-Nighttime sleep is fragmented - disrupted by periods of waking
-Prevalence of 1 in 2000 - diagnosis
-----More people have it - probably 1 in 5 - but is mild

Sleep attack

-Instability in sleep-wake flip-flop
-Stage 2/slow wave/REM

Cataplexy

-Instability in REM flip-flop
-Onset of activity in SLD that activates inhibitory interneurons - sudden onset of atonia (lack of muscle control)
-Typically triggered by strong emotions - happiness, sadness, fright etc.
-Can last a few seconds to a few minutes
-Will pass after emotion dissipates

Sleep paralysis

-Instability in REM flip-flop
-Just as you're falling asleep or right after you wake up
-SLD activates and atonia sets in, so still awake but unable to move
-Can last a few seconds to a few minutes

Hallucinations

-Instability in REM flip-flop
-Happen as you're falling asleep or as you're just waking up

Hypnagogic
-As you fall asleep...
-----Go into REM sleep very quickly - within first 10 minutes... usually takes 60-90 minutes
-----Can happen during periods of high stress

Hypnopompic
-As you wake up...
-----Will not completely come out of REM sleep
-----Experience dreaming while you're awake
-----Can happen during periods of high stress

Narcolepsy causes

-Seems to be caused by deficiency of peptide neurotransmitter orexin (i.e. hypocretin)
-Mutation in orexin B receptor (causes canine narcolepsy) - in dogs
-In humans - complete absence of orexin in 7 out of 9 people with narcolepsy
-Most are born with orexin, but during adolescence the immune system may attack these neurons and symptoms begin

Modafinil (Provigil)

-orexin agonist
-Boosts levels of orexin
-Not effective for those who have no orexin at all - can't produce orexin

Methylphenidate (Ritalin)

-dopamine and norepinephrine agonist (reuptake inhibitor)
-More dopamine and norepinephrine - arousal system stimulated and level of stimulation is maintained for longer periods

Amphetamine

-dopamine and norepinephrine agonist (reuptake inhibitor)
-Maintain level of arousal and stimulation throughout the day

SSRIs and SNRIs*

-Help to reduce episodes of REM sleep components (i.e. episodes of cataplexy, sleep paralysis, and hallucinations)
-Typically taken later in the day
-Fluoxetine (Prozac, Sarafem, others - SSRI)
-Venlafaxine (Effexor - SSRI)
-Atomoxetine (Strattera - SNRI)

Tricyclic antidepressants

-Target norepinephrine, dopamine, and serotonin
-Typically taken later in the day
-Help to reduce episodes of REM sleep components (i.e. cataplexy, sleep paralysis, and hallucinations)
-Protriptyline (Vivactil)
-Imipramine (Tofranil)

Sodium oxybate (Xyrem)

-CNS depressant that reduces excessive daytime sleepiness and cataplexy
-Taken at night, immediately before bed
-Second dose 3-4 hours later (middle of the night)

3rd month of first trimester

we see physical changes that show differentiation into male or female genotype and maybe phenotype

Fertilization

Sperm cell + ovum = zygote
Total 46 chromosomes

Sperm and ovum each have 23 chromosomes

Sex-detemining region of Y (SRY)

-Located on Y chromosome
-SRY gene contains coding for protein Testis Determining Factor (TDF) (Needed to stimulate growth of testis)

-If Gene missing/mutated - no TDF
-If Gene ends up on X chromosome - TDF is produced
-If segment that contains SRY gene is present... genotype is that of typical XY male
-If segment that contains SRY gene is missing/translocated/mutated - see different trajectories of development
-----XX male - phenotypically male but genotypically female
-----XY female - phenotypically female but genotypically male

Swyer syndrome

-46 chromosomes, XY genotype
-Prevalence approximately 1 in 80,000 (NIH estimate)
-15-20% SRY gene mutations or missing segment containing SRY gene
-----No TDF

Results
-Appearance is female (phenotype)
-Functional female genitalia, vagina, uterus, and fallopian tubes
-Non-functioning gonads (streak gonads)
-----Discoloration and scar tissue on ovaries
-----Don't go through puberty because ovaries are completely disabled
----------Usually identified when individuals are supposed to go through puberty
-----Can use hormone treatment to go through puberty and will need it their entire lives
-Typically raised as female and report female gender identity

46 chromosomes, XX testicular disorder

-Translocation of genetic material between chromosomes
-SRY gene is misplaced onto X chromosome
-Prevalence approximately 1 in 25,000 (NIH estimate)

Results
-Typically "normal" development of male genitalia
-Some affected individuals have ambiguous genitalia
-----Not obvious whether they are male or female
-Smaller testes and infertility
-Typically raised as males and report male gender identity

diffferentiation in primordial gonads

-occurs in the 2nd or 3rd prenatal months

-SRY gene present and producing TDF - medulla of primordial gonad develops into testis
-Need hormones/genetic input for medulla to take over and form testes

No TDF (missing/mutated) - cortex of primordial gonad develops into ovary
Ovaries develop by default - do not need any hormones or genetic input for ovary to develop

Differentiation of ducts

Start out with 2 sets of ducts - Mullerian (female) and Wolffian (male)

Mullerian

female duct, uterus, vagina

Wolffian

male duct, seminal vesicle, prostate

development of testis

-Mullerian-inhibiting substance (MIS) and testosterone are synthesized and released to prevent development of Mullerian ducts
-----If MIS is not released...Mullerian system will develop by default
-Testosterone must be present to stimulate development of Wolffian ducts
-5-alpha reductase converts testosterone into dihydrotestosterone
-----Dihydrotestoserone is required to stimulate growth of external genitalia

Hermaphroditism

-Has both internal male and female organs

5-alpha-reductase Deficiency Syndrome

-Guevedoces of Salinas - "penis at 12"
-Group of families that had a disorder that caused children to appear female at birth
-----When they reach puberty, they begin to grow a penis and develop a scrotum and testes
----------Become a male throughout puberty
-----Normal levels of testosterone
----------Hormone levels as children were normal
-Cells organized to develop genitalia but did not get a signal to grow until the individuals reached puberty

Primary sex characteristics

-Organizational effects of hormones (or lack of)
-----Fetal development - stem cells begin to differentiate with genetic switches being turned on and off
-----Cells fit into role of what they will be doing later in development and into childhood and adulthood

Secondary sex characteristics

-Develop during puberty with onset of hormone peaks
-----Facial hair, breast development, voice deepening, menstrual cycle, muscle definition/muscle buildup, growth spurts, hip widening
-Activational effects of hormones
-----Activated by various levels of hormones released during puberty and into adulthood
-----Stimulate further development and growth and regulation of hormonal systems

Female brain

-Higher percentage of gray matter
-----Cell bodies/synapses/more communication between neurons
-----Possibly more neurons or more connections being made between neurons - neurons that are not myelinated?
-Larger hippocampus
-----Memory formation and consolidation
-----Better memory functions? Form LTM easier? Stronger memory? - no evidence
-Larger ventral prefrontal cortex
-----Involved in social cognition and interpersonal judgment
-----Ability to perceive and understand what's happening in a social setting, understand how other people feel, interpersonal relations
-Higher levels of serotonin, dopamine, and GABA
-----Happier? More relaxed? Not necessarily

Male brain

-10% larger cerebral hemispheres - telencephalon
-----Larger skulls
-Higher percentage of white matter and cerebral spinal fluid
-----Myelinated axons
-----More pathways and axons
-Larger and more reactive amygdala
-----More sensitive and easily triggered
-----Greater tendency towards aggressive behaviors - shorter temper, more reactive
-Larger hypothalamus

-Differences may occur as result of higher levels of androgens in males than in females during fetal development*

"Masculinization" of the [rodent] brain

-Males and females each produce testosterone, but males produce more testosterone at a higher level
------Causes similar changes in brain, but certain parts of brain develop further or show different changes in response to higher testosterone level
------Testosterone may be driving these changes, that's why it's called masculinization

Aromatase

Converts testosterone into estradiol

alpha-fetoprotein

-Produced by fetal liver cells and placenta during fetal development
-After birth, levels drop to almost nothing during the first week of life
-----Remain very low/non-existent throughout adulthood
-----Blood screening - may be correlated with testicular cancer if levels begin to raise again in adulthood
-Binds to circulating estradiol and prevents its entry into brain
-does not bind to testosterone

circulating estradiol vs testosterone

-Comes from mother and fetal ovaries
-More testosterone gets to neurons than estradiol... --which results in differences we see in the male brain
-Females produce less testosterone than males in general, so we don't see these changes - see effects from more estradiol reaching neurons than testosterone

Case of John/Joan

Theory: gender was not influenced by genetics - how we developed/identified was due to nurture

Brian circumcision faced an accident that resulted in a disfunctional penis

Brian was raised as a girl and was on female hormonal treatment when pubirty started

brian never felt like a girl and was "in the wrong body".

HPG - Hypothalamic-Pituitary-Gonadal Axis

the neurophysiological pathway that involves the hypothalamus, the pituitary gland, and the gonads

Oxytocin

-Involved in onset of contractions when labor begins
-----High level of _____ keep uterine contractions going to birth can occur
-Helps to stimulate lactation
-Aka "love hormone"
-----Initiate and enable social bonding
-----Important after birth - maternal instincts
-Increases with sexual activity
-----Partner bonding
Postpartum depression/difficult time bonding with infant/etc - low levels of _____

Gonadotropin-releasing hormone

-Gets into pituitary portal
-Stimulates pituitary to synthesize and release other hormones
-Hypothalmus's __________ cause the release of hormones that travel to the gonads

Follicle-stimulating hormone (FSH)

-Anterior pituitary hormones released by GRH
-Females - involved in ova development - stimulation and development of eggs in ovaries
-Males - maturation and development of sperm
Sperm and egg are developed in follicles
-----Sacs where cells are housed and as they develop, they are released out of the sacs
-Females - estradiol release from ovaries

Luteinizing hormone (LH)

-Anterior pituitary hormones released by GRH
-Involved in stimulation to secrete testosterone
-In men and women, but from different cells
-----Testes - leydig cells: respond to LH - increased secretion of testosterone
-----Ovaries - theca: respond to LH to secrete testosterone
----------Some of testosterone is transported to granulosa cells that convert it into estradiol

Ovulation

-Sudden spike of LH - LH surge - triggers ______
-Causes follicle to burst and releases egg

Gonadal hormones

Hormones produced by the testes in the male and ovaries in the female

Androgens

E.g: Testosterone
Females
-Secreted by theca cells
-Testosterone not converted to estradiol is important for hair growth, muscle and bone mass, and repair of reproductive tissues
-Much lower levels than men
-Men usually have much larger muscle mass and bone density

Males
-Sperm maturation - especially after they are released from follicles
-Secondary sex characteristics that occur during puberty
-----Hair growth, voice deepening, muscle strength, development of penis, libido

Estrogens

e.g: Estradiol
Females
-Helps to mature egg after it begins to develop - later stage maturation of ova
-Thicken uterine wall to prepare uterus for potential pregnancy
-Related to sex drive/libido

Males
-Interacts with testosterone to help moderate libido
-Involved in sperm production - interacts with testosterone
-Correlated with erections
-----Erectile dysfunction - low levels of estradiol

Gestagens

e.g: progesterone
Female
-Prepares uterine lining for pregnancy - thicken and cause chemical changes in uterus to allow for implantation
-Interferes with and reduces or blocks uterine contractions so pregnancy can be maintained when it begins
-Aka "pregnancy hormone"
-----Most critical hormone - levels must be maintained at a high level to maintain pregnancy
-----Miscarriages - failed mechanism regarding progesterone
----------If progesterone levels drop below a certain level, then a miscarriage will occur

Male
-May be related to development and creation of sperm - spermiogenesis
-Precursor to testosterone

Menstrual cycle/ovulation

-Normal cycle is about 28 days
-----Can change depending on stress, body mass, outside factors, medication, etc.

Menstruation (1-5)*

The shedding of the uterine lining

Preovulatory phase (6-14)

-First day of menstruation
-Increase in FSH in preparation of ovulation from increased pulsing of hypothalamus
-Responsible for initial development of primary follicle (follicles with eggs that you are born with)
-A few grow/mature into secondary follicle
-----Multiple can result in twins, triplets, etc.
-FSH causes estradiol levels to increase
-----FSH levels lower once process starts
-Estradiol matures follicle and turns the secondary follicle into a graafian follicle
-----Holds mature egg - can survive and can be fertilized
-----Day 11-13
-Rise in estradiol feeds back onto pituitary and hypothalamus that further stimulates hypothalamus to create more GRH and pituitary to release more LH
-LH surge in response to peak of estradiol
-----Occurs around day 12-14
-Ovulation in response to LH surge
-----Day 15-18