Love trust and the neurohypophysis

Question 1

Do all hormones travel in the blood stream? Potential mechanisms?

Answer 1

o	Some (small amounts) hormones pass from the blood stream into the CNS: radiolabelled hormone uptake 
–	less than 1% of iv OT crosses from blood into CNS Paracellular transport? 
V1a receptors in brain endothelial cells
Endocytotic uptake?

Question 2

What is oxytocin thought to act via?

Answer 2

Vasopressin and oxytocin are both relatively small molecules. It is thought that oxytocin must act via the V1aR. as NO OT RECEPTORS CAN BE FOUND ON POST MORTEM.

Question 3

Where do OT/VP nerve pathways go to? And start

Answer 3

In PVN, magnocellular go to neurohypophysis and parvocellular to CNS targets

Question 4

Which nuclei are OT/VP in?

Answer 4

PVN, supraoptic and suprachiasmatic

Question 5

What is one of the means by which VSP/OT enter the CSF?

Answer 5

VSP/OT present in dendrites, dendrites terminate on the wall of the ventricle. Some of these dendrites are present in CSF meaning that vsp and oxytocin could be released, then travel through to target neuron

This was confirmed using Electron microscopy.

Question 6

What experiment was there to show VSP entering CSF?

Answer 6

Intraperitoneal injection of hypersaline solution, major stimulus for VSP. Take back up the fluid released from these neurons and analyse. As the vsp in plasma increases, there is a gradual increase in vsp being released from dendrites into supra-optic nucleus

Question 7

What experiment was there to look at the firing of vasopressinergic neurons?

Answer 7

Looking at firing activity of vasopressinergic neurons. Gave VSP or v1a receptoer antagonist. When they gave vsp, it is followed by an inhibition of firing of vsp neurons in that area
An antagonist by microdialysis, lose that inhibition and there is a massive increase in firing rate
VSP relseased from dendrites and having a local effect on neurons. It is auto-inhibitory

Question 8

Where are VSP/OT receptors in the CNS?

Answer 8

Widely distributed • Prefrontal cortex (OTR)
• Olfactory bulb (ViaR) - Many more animals likely to use olfaction for identification of food/animals than humans
• Corpus striatum (internal capsule + basal ganglia) (OTR)
• Ventral Pallidum (V1aR)
• Nucleus accumbens (OTR)

Question 9

How does the overall pathway look?

Answer 9

Environmental cue>sensory input>eg PVN neurons>VP/OT>VPR/OTR> motor pathways> behavioural pathways

Question 10

What are the vasopressin and oT behaviours generally dependent on?

Answer 10

Background of gonadal steroids. Sex and species specific.

Question 11

What social behaviours are included in VP/OT pathways?

Answer 11

Social behaviours include:
Social recognition
memory
Pair bonding (mating facilitates)
Parental care
Aggression
Anxiety-like behaviour

Question 12

What species does experimental data come from?

Answer 12

o Prairie vole – monogamous
o Montane vole – promiscuous
They have different receptor distributions in the CNS o Promiscuous have oxytocin receptors in the nucleus accumbens whereas monogamous vasopressin in ventrum pallidum

Question 13

What happened to the promiscuous vole when vsp or vp receptor antagonists were given?

Answer 13

No change in behaviour

Question 14

What happens when neurohypophyseal hormones were given to monogamous vole?

Answer 14

Vasopressin given - pair bonding/aggression
VSPRA - blocks above behaviours
OT - no effect

Question 15

What happens when neurohypophyseal hormones were given to monogamous FEMALE?

Answer 15

VSP- maternal behaviour
OT - pair bonding and maternal behaviour
OT knock out - nothing
OTR KO- loss of maternal behaviour

Question 16

What is key in the pair bonding and maternal behaviour?

Answer 16

CRH and CRHR

Question 17

What is a key experiment for investigating VSP pathways?

Answer 17

• Male rats – important of vsp for social recognition. Adult rat in cage, then put in juvenile male rat in same cage. Adult rat investigates juvenile (mainly olfaction). Juvenile removed and then 30 mins later put back in but with another new juvenile. Would expect adult to spend relatively more time with new rat. If juvenile reintroduced 3 hours later, there is extinction. Forgotten about old rat.
• Adults treated with vehicle or v1b r antagonist. If treated then less time spent investigating new rat if vsp blocked.
EG USING DIPTHERIA TOXIN IN OLFACTORY BULB

Question 18

What did the battleboro rats show?

Answer 18

Brattleboro rats, ViaR KO mice

Diminished social recognition of previously recognised individuals

Question 19

What do a strain of aggressive rats have?

Answer 19

• One group high anxiety bred and the other low anxiety bred. VSP MRNA higher in the more stressed rats that mirrors the degree of aggression shown

Question 20

What might the VSP/OT pathways be involved in?

Answer 20

VP/OT may be involved in linking social recognition (e.g. olfactory, mating) to dopaminergic reward system and memory

Question 21

What genetic link is there?

Answer 21

Single nucleotide polymorphisms and characteristics that seem to run in familes.

Question 22

What has oxytocin previously been described with? Evidence

Answer 22

Oxytocin has been described with trust and generousity, reduces anxiety and fear. Effect of oxytocin on males, shown photographs of a scary person or situation. Parts of the brain associated with fear, the amygdala. If you look at a scary face and given a placebo, amydgala. If given oxytocin then there is reduced lighting up showing reduced fear.

Question 23

What clinical application is there for these pathways?

Answer 23

Autism = decreased social functioning, communication, repetitive behaviours and restrictive practices
OT processing defect in CNS?
low p[OT] = decreased awareness of social relationships?
OTR gene mutations (SNPs) associated with autism
V1aR gene mutations (SNP) associated with autism

iv OT to patients in autistic spectrum with repetition disorders; associated with reduction in these behaviours (Hollander et al., 2003)