HYPOTHALAMUS 1 &2 Flashcards
What does the hypothalamus do?
- Secretes hormones into the blood
- Has current state, sensory detector which then compares to set point goal
- If too high, or too low then correction mechanism e.g. dilate blood vessels.
Where is the hypothalamus situated and what is it comprised of?
- Sits on either side of the third cerebral ventricle (wall of ventrical)
- Comprised of thin sheet of tissue in human (3-4mm either side of ventricle)
What types of neurons are in the paraventicular nucleus?
- Magnocellular neurons (larger) (lateral from median eminence)
- Parvocellular neurons (smaller), (medial to median eminence)
Where does the median eminence sit?
- Base of the third ventricle
What is special about the portal blood vessels in the median eminence?
- They are FINESTRATED (tiny pores in them) that allows substances to get in and out of blood vessels (this is unusual acception because blood-brain barrier usually so tight)
What is the hypothalamus connected to the pituitary by?
- Infundibulum (stalk comprised of nerve fibres)
What is the pituitary gland divided into?
- Anterior ( pars distalis)
- Posterior (pars nervosa)
What is the general function of the anterior pituitary gland?
- “master gland”
- Sends messages to the thyroid, adrenal and mammary gland
- BUT controlled by hypothalamus
What do parvocellular neurosecretory cells produce in the paraventricular nucleus of the hypothalamus?
- Neurohormones (releasing factrors)
- These are released into the vicinity of portal vessels (in median eminence)
- Then transported to the anterior pituitary
Which cells are in control of the anterior pituitary lobe?
- Parvocellular neurosecretory cells
What do neuro-hormones transported to the anterior pituitary cause?
- Release of hormones from specialised secretory cells
What are the releasing factors released from paraventricular nucleus neurons?
- GnRH- Gonadotropin releasing hormone
- TRH- thyrotropin releasing hormone
- CRH- corticotropin releasing hormone (peptide)
- GnRH- Growth Hormone Releasing Hormone
What do portal vessels do?
‘Port’ releasing hormones (GnRH etc) down through the small circulation into ANTERIOR PITUITARY
- Vessels are finestrated so releasing facors can EXIT circulation in vicinity of cells in anterior pituitary
Which types of cells are responsive to GnRH?
- FSH (follicle stimulating hormone) prodcing cells
- LH (leutenising hormone) releasing cells
Which types of cells are responsive to CRH?
ACTH (AdrenoCorticoTropic Hormone) producing cells
Which types of cells are responsive to TRH?
TSH ( thyroid stimulating hormone) producing cells
Which types of cells are responsive to GHRH?
- GH (growth hormone) producing cells
What hormones are part of gonadotrophs and what is their target?
- FSH and LH, exits the anterior pituitary to work on gonads/reproduction
What hormones are part of Thyrotrophs and what is their target/function?
- TSH- after being released from anterior pituitary into blood stream, acts on the thyroid
- Function in development and energy expenditure
What hormones are part of corticotrophs and what is their target/function?
- Adrenocotricotropic Hormone (ACTH)
- Works on the adrenal gland and mediates stress
What hormones are part of somatotrophs and what is their target/function?
- Growth Hormone
- Widespread anabolic actions
Are there different cells producing SPECIFIC hormones in anterior pituitary that act on DIFFERENT targets in pituitary?
-YES!!!!!!!!
Where is stress detected and what does it lead to the release of ?
- Physiological, emotional or psychological stress is detected in the BRAIN
- Release of CORTICOTROPIN RELEASING HORMONE (CRH)
Where is CRH released from?
- Nerve fibres originating from neurons in PARAVENTRICULAR nucleus of hypothalamus
What is CRH transported via?
- Portal system down the pituitary stalk
Where is CRH transported to?
- Anterior pituitary via the portal system (pituitary stalk)
Once at the anterior pituitary, what does CRH act on and what is released from this?
- CRH acts on CORTICOTROPHS
- Causing release of Adrenocroticotropic Hormone (ACTH)-AKA corticotropin
What does ACTH act on?
- Acts on the cortex of adrenal gland which causes release of CORTISOL
What does cortisol do?
- Circulates in bloodstream and mobilises energy stores and supresses the immune system
Where is GnRH produced?
- Neurons in preoptic area of hypothalamus
What is GnRH activity like and what factors is it under feedback control by?
- Pulsatile (rhythmic) activity
- Feedback control of some hormones
- Also light stimuli (day length)–> some animals sync mating with day length
Where is GnRH released into and what does it act on?
- Released into portal system
- Acts on gonadotrophs in anterior pituitary (LH release, FSH release)
What do FSH and LH do in males?
- Produce testosterone and sperm
What do FSH and LH do in females?
- Cause oestrogen release (cyclic release of LH and FSH- mestrual cycle)
What does the POSTERIOR pituitary have to do with?
- Control of vasopressin and oxytocin release
What is another name for vasopressin?
-Anti-diuretic hormone
When is vasopressin released in Magnocellular neurons?
- In response to hemorrhage or dehydration
What happens when you are dehydrated?
- Increase in tonicity (osmality-conc.) of blood
- So plasma sodiums increase and this acts on OSMORECEPTORS (just in front of the hypothalamus)
Where do the sensors send neural connections?
- To MAGNOCELLULAR neurons in the paraventricular nucleus that contain VASOPRESSIN
What happens when you have a haemorrhage?
- Same mechanism as dehydration
- BUT cardiac volume receptors activated
- Angiotensin II released
What does angiotensin II do in relation to hemorrhage?
- Acts on sensors in the brain that feeds into MAGNOCELLULAR neurons to produce VASOPRESSIN which leads to a feeling of thirst to help increase blood volume
What are the similarities and differences in the losing blood and dehydration pathways?
- DIFFERENT STARTING POINTS (osmoreceptors and angiotensin II) but the SAME END POINTS (magnocellular neurons to release vasopressin)
How is the posterior pituitary mechanism different to the anterior pituitary?
- After VASOPRESSIN, magnocellular neurons are activated
- Vasopressin is taken down axons (without stopping in median eminence)
- Goes straight to posterior ptuitary where it is dumped DIRECTLY INTO THE CIRCULATION (different to anterior)
- Then goes out into bloodstream and it goes to kidneys to reduce urine output
What is the difference between oxytocin and vasopressin?
- Oxytocin is STILL produced in the paraventricular nucleus, STILL MAGNOCELLULAR but produced in DIFFERENT NERVE FIBRES and has DIFFERENT FUNCTIONS to vasopressin
What happens when a baby is suckling?
- Causes activation of sensory receptors in breast
- Sends info via the spinal cord up into hypothalamus where it acts on OXYTOCIN containing neurons in PARAVENTRICULAR nucleus
- Then goes down axons, gets released into blood vessels and taken out into peripheri
- Acts on breast to let down milk and also acts on uterus to cause contractions (especially when oxytocin receptors build up before childbirth)
Are there also emotional impacts on the same oxytocin neurons?
- YES!
- They don’t come from the simple reflex
- Happens for lactating mums recognising baby crying that isn’t theirs
What happens if an animal lacks vasopressin gene?
- Urinates all day
Are vasopressin and oxytonin produced by magnocellular neurons in posterior pituitary of ?
- In the MAGNOCELLULAR neurons of paraventricular nucleus
Are vasopressin and oxytocin also produced in parvocellular neurons? 0
- YES! But are very different in these cells -acts as TRANSMITTER in brain to cause certain effects
What do ocytocin and vasopressin have to do with in the parovocellular neurons of posterior pituitary and what is an example of this?
- Love, monotony
e. g. In prarie voles, monotomous, mutual grooming, looks after babies equally - Oxytocin and vasopressin released
Are oxytocin and vasopressin released in the montane vole?
- NO!
- These voles have different distribution of receptors
- One night stand mating and don’t look after babies at all really..
What is the important factor during sexual activity important for forming a MONOGAMOUS pair bond with partner?
- OXYTOCIN released into brain (from parvocellular, oxytocin containing neurons) from female during sexual activity
- VASOPRESSIN seems to have a similar effect on males
What is another thing that oxytocin can activate?
- reward pathways in the brain (release dopamine)
What can activation of reward pathways (in ventral pallidum) consolidate after mating?
- Partner preference
What is the human implication for magnocellular release of oxytocin?
- Female reproduction
- Released in large amounts during labour and suckling - Facilitator for childbirth and breastfeeding
- Stimulant used to induce labour and speed up contractions
What is the human implication for parvocellular release of oxytocin?
- Potential role in orgasm. social recognition, bonding, maternal behaviour
- Potential increased trust in people
- Oxytocin higher in people who claimed to be falling in love
What does oxytocin trigger the release of in reward pathways?
- Dopamine and serotonin in, heightens feelings of intimacy and trust (even in strangers)
Where is integration of endocrine and autonomic functions centred in?
- Paraventricular nucleus of hypo
- Heart blood vessel, kidney, brown fat, adrenals are also mediated by the sympathetic nervous system **
What is known as the ‘feeding centre’ ?
The lateral hypothalamus
What is known as the ‘satiety centre’?
- The ventromedial hypothalamus
What is the lipostatic theory? (1960s)
- Action between peripheri and brain in setting body weight
- Brain monitors amount of body fat and acts to ‘defent’ THAT set amount of body fat (energy stores) from changes
- Likely to be a link or messenger between body fat and brain
- Messenger is a product of gene expressed in fat (OB gene)
What does OB gene product do?
- Circulates in blood and tells brain the extent of fat in the body
What is the name for the factor circulating in the blood letting the brain know the extent of fat in the body?
- Leptin (greek–> lepto=thin)
- Increased metabolic weight
- Decrese in glucose and insulin
What was leptin a good fix for?
- People that lacked the OB gene to produce leptin (didn’t benefit those that had a fine gene-so can’t cure obesity epidemic)
Leptin will inhibit…
..neurons that promote feeding
Leptin will excite…
..neurons that inhibit feeding
What is the circuitry mediating LONG TERM energy balance?
- Satiety centre in medial basal hypothalamus (1960s knowledge)
- BUT not just satiety centre- that is the overall response that can be produced
- Within it there are a number of competing drives (to eat or not to eat)
Where is the arcuate nucleus?
- Near the 3rd cerebral ventricle at the base of hypothalamus (near midline)
Which types of neurons are in the arcuate nucleus?
Neuron that contains: Neuropeptide Y (NPY) + Agouti Related Peptide (AgRP)
- These produce an “orexigenic” effect (promotes feeding)
- Second neuron (different set of neurotransmitters)
- Contains Proopiomelanocortin (POMC) + Cocaine Amphetamine Regulated Transcript (CART)
- “Anorexigenic effect” (prevents feeding)
What does an oxigenic effect mean?
- Promotes feeding
What effect do NPY and AgRP have in the arcuate nucleus?
- “orexigenic” effect (promotes feeding)
What effect do POMC and CART have in the arcuate nucleus?
- “anorexigenic” effects (prevents feeding)
What is the motivation/predisposition to feed based on?
- “dance” between the two types of neurons in the arcuate nucleus (relative activity of two neurons)
What occurs in starvation?
- Inhibitory break on peptides that promote feeding (NPY and AGrP) is removed
- So feeding is stimulated (in lateral hypothalmic area) and there is reduced leptin to try and get back to higher body weight
- Secretion of ACTH and TSH is INHIBITED so decrease metabolic weight
What occurs in INCREASED levels of leptin?
- Activate neurons with alpha MSH (product of POMC) and CART to now inhibit feeding!
- Activate neurons in the paraventricular nucleus that increase metabolic weight
- Drags back down to lower body weight
What does the concept of ‘set point’ of body weight mean?
- If we overeat for a period of time and put on weight THEN STOP, we will move back down to the appropriate (set) body weight.
- If we under eat for a period of time THEN STOP, we will put back ON body weight until set weight is reached.
Why is it so difficult to maintain weight loss in the LONG TERM?
- Because metabolic adaptation occurs
- After week 30, actual energy expenditure is MUCH LOWER than predicted
What is feeling of hunger before breakfast caused by?
- hormone Ghrelin (produced in stomach)
- This rises just before you have a meal
What happens as you have a meal in terms of Ghrelin hormone?
- Levels of ghrelins start to plumet
At the same time when you are having your meal, what signals are being produced?
- Satiety signals (produced in different parts of the gut)
- turned on and can go into blood
- LIMIT food intake (‘i’ve had enough to eat)
Is Ghrelin the ONLY HUNGER hormone?
YES!
What are examples of satiety signals (that regulate body weight) ?
- Cholecystekinin (CCK)
- Insulin
- Gastric Distension
- Leptn
- PYY3-36 (produced from small intestine)
- Amylin (pancreas)
- Ghrelin (from stomach)
What does Gastric Distension do?
- the more you eat food, the more your stomach swells–> sensory nerve fibres sense stretch and relay info to satiety centres in brain that say “I’ve had enough”
How do changes in these hormones AFTER weight loss make it difficult to maintain weight loss?
- Study done: 8 weeks on low calorie diet then return to normal ‘healthy diet’
- compared hormones 4 hours after meals
1. Baseline
2. 10 weeks
3. 62 weeks (about 1 year) - At 62 weeks, Ghrelin levels still elevated (red in graph)
- Satiety hormones (that make you less hungry) normally go up after a meal BUT after 1 year they were still REDUCED! (PYY, Amlyin, CCK)
- in people that have lost weight the desire to eat stays up!
What is one pathway that sets our ‘set point’ of boy weight?
- Things released from gut that act back on brain to modulate amount of energy expenditure there is
- But there are complexities with reward associated with food (executive control from cortex)
What does executive control from cortex affect?
- Impact on motivation to eat, when and how (more cognintive)
What does hedonstic mean in terms of eating?
- Pleasure of eating
What does hedonistic eating involve? ***
- Excitation of dopaminergic neurons arising from ventrical tegmental area and projecting to basal forebrain
What can reward be divided into in these pathways?
- “liking” and “wanting”
What is “liking” about?
- Pleasure
- Hedonic ‘liking’ reactions are stereotypical and preserved across species and exist WITHOUT higher centres
What are the key brain regions and neurotransmitters involved in the “liking” pathway?
- Mediated by MU OPIOIDS acting at receptors in the nucleus accumbens
What blocks “liking” pathways?
- Mu opioid receptor agonist
- Reduces the liking of things that you previously liked
What is the “wanting” pathway about?
- Motivation (not pleasure) (Homeostatic)
- “incentive salience”
What are the transmitters involved in the “wanting” pathway ?
- Dopamine
What does an increase in the dopamine levels in nucleus accumbens cause?
- Does not change “liking” BUT increases the motivational component of reward (wanting-mediated by dopamine)
What occurs in a herroin addict?
- At the start, both the mu opioid (liking) and dopamine (wanting) are there, HOWEVER after a while (chronic over-stimulation)- of pathwat causes homeostatic response so will just be dopamine (but system will be downregulated- addiction)
