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A BMS 381 - Developmental neurobiology > Hypothalamus: love, trust, aggression, addiction > Flashcards

Hypothalamus: love, trust, aggression, addiction Flashcards

1
Q

What animals are instrumental in understanding the role of the hypothalamus in SOCIAL behaviours?

What discovery made looking at these animals?

A

Prievoles

2 hypothalamic neurons important in social behaviours: Oxytocin+ (Oxt) and Arginine Vasopressin+ (AVP) neurons in the PVN

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2
Q

What are social behaviours?

A

Trust, aggression, empathy, love

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3
Q

Where are Oxytocin+ and Vasopressin+ neurons present and where do they project to?

A

The PVN of the hypothalamus

Project to the POSTERIOR PITUITARY and release hormones directly into the blood stream –> periphery

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4
Q

(ASIDE) What are the other types of neurons in the PVN?

A

Hormone releasing (eg. CRH) - to ME

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5
Q

As well as to the periphery, where do Oxt and AVP neurons project to?

A

To many different target neurons (express receptors) of the brain in complicated central circuits

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6
Q

What is AVP important in?

What is Oxytocin important in?

A

The regulation of kidney function and water balance
Parturition (birth) and lactation

Recent studies show both are highly important in directing social behaviours

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7
Q

How are Oxt and AVP important in directing social behaviours?

A

Through the complex interaction with other brain regions and neurons that are stimulated by these hormones centrally

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8
Q

Who studies prievoles?

What did they find?

A

Carter and Young

Prievoles:
- SOME vole strains form a PAIR-BOND- form close attachment with a mate and males show good paternal behaviour - maintain close bond for rest of lives

  • OTHER strains do NOT form a pair bond - polygamous and ignore offspring
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9
Q

What dictates the behaviour of the Prievoles?

A

1) BALANCE of Oxt and AVP
2) LOCATION of neuorns that express Oxt and AVP RECEPTORS (balance of where neurons receive Oxt and AVP)

(WHERE and HOW MANY neurons are stimulated –> give rise to different behaviours in voles)

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10
Q

Why do some vole strains form pair-bonds?

A

Neurons rich in Oxt receptors are found in areas that govern ADDICTIVE BEHAVIOURS –> become ADDICTED to their mates

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11
Q

What can generate diversity in the brain and sociobehaviours traits?

A

Microsatellite instability:

  • Determines how strongly the AVP RECEPTOR gene is transcribed (expressed)
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12
Q

What is a microsatellite?

A
  • Non-coding enhancer-like regions that control how much of a gene is transcribed
  • Repeated unit
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13
Q

What is the structure of the vasopressin RECEPTOR gene?

A
  • 2 exons (exon 1 and exon 2)

- Microsatellite region upstream of exon 1 - controls how much of the vasopressin RECEPTOR gene is transcribed

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14
Q

What is the difference between the microsatellite region of AVP in different voles?

A

Different NUMBERS of repeat units

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15
Q

What is the difference in function between long and short microsatellite regions?

How was this seen?

A

LONG satellite region - regulates MORE AVP RECEPTOR gene transcription

Seen by:
- Cloning the different satellite regions UPSTREAM of a reporter gene

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16
Q

What is the difference in behaviours of voles with a long or short satellite region?

A

NO DIFFERENCE in:

  • Nesting
  • Nursing posture
  • MATERNAL pup-grooming

SIGNIFICANT DIFFERENCE in:

  • PATERNAL pup-grooming
  • Long satellite region - better fathers (lick and groom their pups for longer)
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17
Q

What are the differences in paternal behaviour with a long satellite region?

How is this seen?

A

Greater probability of SOCIAL ENGAGEMENT and BONDING with other voles

Chamber experiment:

  • Voles to test with 2 chambers: one containing original mate and one containing a new mate
  • See where spends the most time
  • Spend more time with the original vole of whom they are pair bonded
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18
Q

What is the hypothesis with longer satellite regions and AVP receptor activity?

A

Longer satellite regions alter AVP receptor activity

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19
Q

What are the GENOTYPE differences in social behaviour associated with?

A
  • Robust differences in how AVP binds to V1aR in the brains of F1 males
  • Several brain regions –> 50% change in quantity of V1aR binding

Long allele:
- In brain region associated with addiction –> gives a HIGH level of receptor binding

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20
Q

What associates with pair-bonding in humans?

Where was this seen?

A

Genetic variation in the vasopressin receptor 1a gene (AVPR1A):
- Comes in many different forms in humans

Swedish study:

  • Men with 2 copies of one particular form of the gene (homozygous for RS3 334)
  • -> Less likely to married and more likely to report difficulties in their relationships than other men
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21
Q

What does the imbalance of Oxy and AVP cause?

Example

A

Effects on health and wellbeing

Work connects reduction in Oxy functionality?? to addiction and autism

22
Q

What social behaviours does Oxy control?

A

Trust, empathy

23
Q

What social behaviours does AVP control?

A

Aggression

24
Q

What is a new target for substance-use disorders?

A

Brain Oxy system

25
Q

What do drugs acting on the Oxy brain system ameliorate?

A

Range of ADDICTIVE behaviours:

  • Alcohol
  • Stimulants
  • Opioids
  • Nicotine
26
Q

What does Oxy inhibition of drug consumption and drug reward involve?

A

Interference with the brain reward circuitry (in particular dopaminergic systems in the striatum)

27
Q

What does synthetic Oxy cause?

How?

A

Interference with stress responses and socioemotional impairments during protracted withdrawal

Inhibits stress-induces relapse by compensating for impaired Oxy functionality and to REBALANCE:
1) The specific dopaminergic pathways

2) Hypothalamic and extrahypothalamic stress systems

28
Q

What is the effect of increases in Oxy on the brain?

A

Enhancement of connectivity between:

1) The frontal cortical regions
2) Amygdala and Nucleus Accumbens

–> Criticial to Oxy effect on relapse by improving inhibitory control over craving and cue reactivity

29
Q

How are their differences in key neurons?

A

Over life and in sex-specific manner

30
Q

What do sex differences in behaviour come from?

A

Assumed arise from sexual dimorphism in the underlying neuronal circuits

31
Q

Examples in sex differences in behaviour in mice?

What is different in the brains of these mice?

A

When exposed to alien pups:

  • Virgin females behave maternally
  • Males attack or ignore the pups

Differences:

  • TH expressing neurons in the AVPN of the mouse hypothalamus are more numerous in mothers than in virgin females and males
  • -> Governs paternal behaviours in a sex-specific manner
32
Q

What happens in female mice if ablate the AVPN TH+ neurons?

A

Impairs maternal behaviour

33
Q

What happens in female mice if optigenetically stimulate/increase AVPN TH expression?

A

ENHANCES maternal care

34
Q

What happens in mice if reduce TH in mice females?

Increase TH?

What is the conclusion from this research?

A

Reduce:
- Reducing circulating Oxy

Increase:
- Increasing circulating oxytocin

Conclusion:
- AVPN TH+ neurons control oxycytocin secretion and maternal care

  • Causal relationship between sexual dimorphism in the adult brain and sex differences in paternal behaviour
35
Q

Where do AVPN TH+ neurons have a monosynaptic connection to?

A

Oxy+ neurons in the PVN

36
Q

How does the AVPN TH+ neurons effect males?

A

No effect on paternal care but SUPRESSES inter-male aggression

37
Q

How does the body deal with pregnancy in a mouse?

A

In a female, get new neurons born as needed to support pregnancy –> neurons born in order to ANTICIPATE change and prepare the body optimally for changes

38
Q

What are the VMN and DMN of the hypothalamus involved in?

A

Agressive behaviours

39
Q

What is another reason why are male mice more aggressive than female mice?

A

Male mice have a class of neurons that make them more aggressive - females don’t

40
Q

How can you show a particular neuron/circuit is involved in a certain behaviour?

A

OPTOGENETICS:

- Can activate a neuron expressing the Chr2 gene –> activate a circuit

41
Q

What is critical to function of a neuronal class?

A

NUMBER and LOCATION

42
Q

Where is the telencephalon in comparison to the hypothalamus?

A

ANTERIOR

43
Q

What establishes telecephalic and hypothalamic progenitor idenities?

A

Cross-repression between the transcription factors:
1) Foxg1 (telencephalon)

2) Foxd1 (hypothalamus)

44
Q

What do foxd1 progenitors ultimately commit to?

Example? How?

A

Many hypothalamic neuronal identities

Example:

  • AVP and Oxy neurons
  • Foxd1 progenitors divide and become differentiated –> give rise to more progenitors etc.
  • GRADUAL REFINEMENT from foxd1 cell –> neurons of specific nuclei
45
Q

What does the absence of Foxg1 cause? (homozygous)

A

Death (embryonic lethality)

46
Q

What does the absense of Foxd1 cause? (homozygous)

A

Viable

But display microcephaly, altered hippocampal neurogenesis, behavioural and cognitive defects

47
Q

What is the hypothesis if have ONE copy of foxg1? (heterozygous)

Why?

A

Have MORE hypothalamus –> MORE Oxy and AVP neurons

Due to:

  • Less foxg1 protein
  • Less repression of the foxd1 protein
48
Q

How was the increase in Oxy and AVP neurons validated?

What did this show?

A

Immunohistochemistry:
- Showed the number of cells set aside to be telecephalic might be in competition with the number of cells set aside to become hypothalamic

49
Q

Why need accurate balance between foxg1 and foxd1 expressing territory?

A

To balance higher cognitive function with autonomic function

50
Q

What is TH?

A

Tyrosine hydroxylase - a marker for neurons involving the dopaminerigic neuorns

A BMS 381 - Developmental neurobiology (17 decks)

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