Neuro Test 3

Endocrine (ductless) gland examples

Pituitary glands: hormones in blood

Gonads: testes and ovaries, sex hormones

endocrine glands location

hypothalamus

pituitary gland

gonads

hormone vs NT

same: release response, chemical transmit

hormones dif:

1. Large amounts

2. target tissue far from release sit

3. into blood

4. long lasting

5. long term readiness to respond

3 Classes of hormones

amino acid derivative hormones

peptides hormones

steroid hormones

amino acid derivative hormones

amino acid single

epinephrines: adrenaline

peptides

amino acid chains

bind to metabotropic receptors (indirect change thru cascade) on cell membrane

steroid hormones

enter cell nucleus and directly influence gene expression

what are gonadal hormones

sex hormones

steroid

produced by gonads

regulated by gonadotropins (via pituitary)

adrenal cortex: releases gonadal hormones in small amounts

3 classes of gonadal hormones

androgens

estrogens

progestins

androgens

released by testes

ex) testosterone

males higher concentration

estrogens

released by ovaries

ex) estradiol

high conc females

first half cycle!

Progestins

released by ovaries

ex) progesterone

high conc femails

second half cycle and uterine lining!

hormones released by

hypothalamus: regulates release, MASTER GLAND of master gland

• releases: ‘releasing hormones’

pituitary gland: anterior and posterior

Anterior Pituitary

gland

hypothalamic hormones arrive by hypo-pituitary portal system

release/makes: TSH,LH,FSH,ACTH,Prolactin

regulation (metabolism, stress, reprod, etc.)

Posterior pituitary

DIRECT input from thalamus

PVN and SON: hypothalamic nuclei that link CNS to endocrine system

releases/stores: oxytocin and vasopressin

control water balance and reporoduction

sexual devlopment influenced by

androgens (testosterone)→ wolffian system

estrogems (estradiol)→ Mullerian system (indirect because absence of testosterone)

6 week gustation, embryo contains what gonads

potential to develop both

bipotential (primordial) gonads

• bipotential gonads are a tissue, not a set

external organs develop from bipotential tissue

gonads XX and XY identical (no physical dif)

Contain at 6 weeks:

glans

urethral folds

lateral body

labioscrotal swelling

3rd month gustation: INTERNAL reproductive ducts male

wolffian system develops:

• seminal vesicles: semen

• vas deferenes: sperm transport

• prostate: semen and urinary function

develops:

• male fetus

• orchidectomized male fetus (castrated, no testicles)

develop because produce mullerian inhibiting substance

3rd month gestation INTERNAL reproductive ducts female

default mullerian (doesn’t require estrogens!!):

• uterus

• vagina

• fallopian tubes

develops:

• female fetus

• ovariectomized female festuse (no ovaries)

3rd month gestation males EXTERNAL REPRO ORGANS

head of penis

shaft

scrotum

3rd month (12 week) gustation female EXTERNAL REPRO ORGANS

clitoris

labia minora

clitoral hood

labia majora

Just after conception

have both repro ducts (wolf and mull system)

Not both: true hermaphrodite not possible

Phenotypic sex develops btw

7-12 weeks GA

at 6 weeks: males start to release SRY protein (from Y chromosome)

• begins differentiation of gonadal tissue (can’t see yet)

12 weeks shows phenotype differentiation:

• female (no SRY) cortex thickens→ develops ovary

• male: medulla thickens (stringy)→ develops teste

(7-12 weeks: differences and brain differences)

Sexually dimorphic brain areas

brain males: 15% larger

hypothalamus dif:

• females: cyclical hormones

• males: steady state hormone release

Aromatization hypothesis

masculinized brain due to estrogen

conversion of testosterone to estradiol

ONLY testosterone to cross BBB into cerebrospinal fluid (produces estradiol that influences gene expression, through aromatization)

• Not cross: estradiol (usually) and alpha fetoprotein, which can bind with estradiol, trapped in periphery!

Puberty (10-15, less for females)

hypothalamus releases LHRH

LHRH to pituitary gland, which releases LH and FSH, which releases testosterone and/or estrogen

Perinatal testosterone (Guinea pig test)

masculinizes sexual (copulatory behavior)

effects when testosterone before birth

mounting: men rat

lordosis: female rat

guinea pig test: +T= ovariectomized females, more mounting with testosterone, less lordosis even if injected with progesterone/estradiol

Gonadal hormones influence sexual behavior differences m/f

orchidectomy/castration: decrease desire, variable (asexual, or others retain sexual ability)

• testosterone replacement can restore behavior but only to previous level

females: hormone level/cycle NOT = sexual receptivity

• ovariectomy eliminates fertility and lubrication but not motivation

• T and E2 contribute to sexual desire

Four brain structures sexual activity

1. cortex: complex aspects sexual experience

2. ventrial striatum: anticipation and experience/pleausre

3. hypothalamus

• F: ventromedial nucleus: sexual behavior

• M: medial preoptic area: sexual behavior

• 3rd Interstitial nucles (INAH-3): larger in males

4. amygdala: mating partner identification

More common in males

autism

adhd

parkinsons (movement)

more common in females

depression

anxiety

alzheimers (memory)

4 Cases of Human Sexual Development

1) CAH: low cortisol and high androgen (growth and fertility and genital issues and diff)

2) 5a reductive difficiency

• in dominican republic

• converts testosterone to DHT (5aT)

• lacks 5a reductase at prenatal

• Proscar: 5a reductase inhibitor treatment that also treats baldness

• F APPEAR at birth

3) Androgen Insensitivity Syndrome (AIS)

• puberty: secondary sex chrctrstcs of females develop

• diagnosis: infancy ambiogous gentalis (partial), adolescent primary amenorrhea (complete), infertility

4) John/Joan: penis remove

MAMAWAWA issue

gentic sex binary

phenotypic sec not binary (not 1:1 with genetics)

psychosexual identity

Intersexed persons

CAH and AIS (maybe 5a)

chronobiology and chronotype

bio clocks and rhythms study

chronotype: tendency sleep time

Circadian rhythm defs

amplitude: height

period: length

phase: dot

Biological rhythms are

endogenous: biologically w/n

entrainable: synchronizable

free running period

daily running period without cues

23.5-24.7 hrs (s-w cycle)

-rodents: active at night, 24 hr rhythm even if dark all day

Photic phase

response relationship

clock shifts with dim light

rats: active at night

• light during day: no change

• light early in night: delays activity

• light later in night: advances activity (later in night because early morning)

SCN

master clock

blue light: activates ipRGcs in retina (in retinal ganglion cells)

• melanopsin is a photopigment sensitive to blue light

• ipRGSC axons form retinohypothalamic tract and excite SCN

proof: lesions hamster, make arrhythmic (noncontinuous) activity, fix by SCN transplant

Visual Pathways

- Hypothalamus

• SCN

- (Superior Colliculusth): eye movement path

- retinohypothalamic tract (retinal gang ipRGC to SCN)

ipRGCs consist of

glutamate and PACAP

Brainstem to SCN track

5HT

behavior context for entertainment signals

thalamus to SCN track

NPY

photic and nonphotic stimuli integration for entertainment

Output of SCN

to thalamus and hypothalamus

outputs:

body temp

sleep wake cycle

hormones

Melatonin for Pineal Gland (S-W cycle)

darkness indication

ipRGCS activate SCN, then SCN inhibits pineal gland activity (lowers melatonin in blood)

Clock Gene Circadian Rhythm

1. CLOCK ( and BMAL1) binds to promoter: induces per gene expression

2. PER (and cry) builds up in cytoplasm

3. PER enters nucleus, inhibits CLOCK from binding to DNA (PER expression blocked)

4. PER degrades. CLOCK rebinds and restarts per expression

PER: sleep promote (low active at night)

cry: awake

Sleep Needed

10-18 old: 8-10

18+: 7-9

(decreases with age)

ALL MAMMALS NEED SLEEP

some unihemispeheric: one side brain sleep, birds and dolphins

sharks move while asleep

Polysomnography (PSG) sleep measured types (reveals 4 stages of sleep)

EEG: brain activity

EOG: eye movement

EMG: muscle movement

4 Stages of sleep

non Rem: N 1,2,3

Rem

hypnogram shows

Non rem stages

N1: alpha to theta

N2: thetwa waves, sleep spingles, k complexes (spikes)

N3: deltas, slow waves

What drives when we sleep

Process C: circadian rhythm (activity low at sleep)

Process S: sleep pressure (heightens before asleeep)

Lesions that localized the ascending arousal system

Cervaue isole: at midbrain, persistent sleep state

Encephale isole: btw medulla and spinal cord: normal SW cycle

Reticular formation: wakefulness producing areas btw cuts

ARAS system (Retic form: awake, supplies cortex with arousal transmitters vs VLPO )

Bottom to top

1. NE

2. 5HT

3. LDT/PPT (Ach)

   1. TMN (histamine)

4. VLPO (GABA,galanin)

5. thalamus

wake and sleep inhibit each other

Sleep: low VLPO, high TMN, Rn, LC, PPT

sleep transition flip flop switch

Awake: high VLPO, low TMN,Rn,Lc,PPT

Insufficient sleep causes

cognitive impair

memory loss

increased risk: heart disease, obesity, Type 2 diabeties

Sleep Disorders

Social Jet lag: week and weekend poor sleep quality and chronic partial sleep deprivation

insomnia: 30% adults, cant stay or fall asleep. F over M (low T ), common in menopause

• treat: hypnotics, CBT, TCA, melatonin small benefit

sleep apnea: breathing

• obstructive/ OSA: airway block

• central/ CSA: brain fails signals to breathing muscle

RLS: genetic, lifestyle, iron deficient, alcohol,coffee

Narcolepsy: daytime sleep, cataplexy (collapse), hallucinate, sleep paralysis

• Rem onset fast during day naps

• stimulants: provigil,ritalin,addeal (methyl and amphetamine)

• hygiene, work, scheduled naps

Route of bodies with a substance

absorption: in blood

distribution: active and inactive sites

metabolism

elimination

BBB

lipid soluble drug

entry into brain tissue from circulatory system

once in CNS influence neural activity

Alcohol route body phases

absorption: stomach into blood

distribution: cross BBB LOW GLU HIGH GABA R

metabolism: liver

elimination: breath and urine

Dose Response Curve/tolerance

small effect small drug amount curve patter (initial)

tolerance: more drug exposure (neuroadaptations: tolerance, can cause seizures none) less effect

Types of tolerance

functional: brain and NS less desired response

metabolic: liver more efficient

Contingent tolerance

tolerance to experienced drug effect,

tolerance convulsion (seizures, usually from alcohol) higher when drug given before task

conditioned tolerance

tolerant more when in presence of drug (US) predictive area (CS)

not CR

Addiction categories

Physical dependence

• cocaine and cannabis minor physical

compulsive behaviors

-compulse drug seek and use

cravings and relapse

addiction is behavioral (compulse and craving) and chronic, relapsing (long lasting, relapse cycle)

Addiction potential, influenced by route of administration

meth-morph-heroin

coc leaves-cocaine-crack

nic patch-snuff-cigars

rapid absorption leads to fast onset and shot duration

Stages of addiction

initial taking: social, available, novelty, non-drug reinforces

habitual: like vs want, hedonic (like) vs positive incentive (want), incentive sensitization

craving and relapse: stress, drug priming, drug cues (CS)

Alcohol

acute tolerance: diminish sensation but still effected (metabolising slow)

CNS depressant

mood, judgement, motor incoordination, impairments, death and loss conscious

active site distribution: LOW GLU HIGH GABA

DA

high gaba + high opiod+ low glu= high DA (dopamine)

Cocaine and other stimulants

block dopmamine transporters (DAT) that remove DA from synapse

5 commonly used substances

Tobacco: S

alcohol: D

• target: Glu and gaba

• effect: FAS and liver cirrhosis

marijuana: D

stimulants: S

• target: DA transporter

• effect: psychosis

heroin: D

Intracranial self-stimulation (ICSS)

self stimulate sites that activate reward circuits

Olds and Milner

Increasing DA signaling in the mesotelencephalic reward pathway

VTA (R): start, dopamine neuron cell bodies with GABA interneuron attached disinhibited, dopamine release

N. Accumbens (L): DA binds to postsynaptic spine