Lecture 7 Part III Flashcards Preview

PSC 125 > Lecture 7 Part III > Flashcards

Flashcards in Lecture 7 Part III Deck (40)
Loading flashcards...
1

how is GR expression regulated

-GR expression is up-regulated because licking/ grooming activates transcription factors/coactivators involved in turning on GR gene expression.

-Pup licking/grooming from the mother increases NGFI-A expression and binding to the promoter of the GR gene
specifically exon 17

-The increased binding of NGFI-A to the promoter is limited exclusively to the licking/ grooming bout.

2

regulation of the GR gene

-GR gene has a regulatory region and a coding region

-exon 1 of the GR gene includes a number of promoter sequences (1,2,3,4,5,6,7, etc) these are axons that end up in the mRNA sequence
-Also are locations in which transcription factors bind

-Exon 1-7 happens to have a pretty good amount of homology with the region in the human GR gene we called exon 1F

-This is the site that we think is driving the differences in GR gene expression through that NGF1-A transcription factor

3

GR regulation pathway

Moms licking ---> serotonin is released ---> binds to serotonin receptor ---> activation of the signaling cascade ---> activates NGFI-A transcription factors ---> binds neuron specific location where we only see activation within neurons ---> binds to exon 17 of the GR promoter ---> start to get GR transcript

4

how does GR expression persist in adulthood ?

-The same pattern of expression is seen in adulthood

--Is like licking and grooming turns on this knob and from now on pup is going to make more GR receptors and that pattern will continue to adulthood

5

how is the maternal effect renders stable?

-The difference in pup licking between high and low mothers is apparent in the first week of light, but these offspring continue to show altered behavioral and physiological stress responses in adulthood (long after the initial tactile stimulation).

-GR mechanism hasn't been investigated to the same extent in females

-If female is raised in a low LG environment she will also spend little time LG her offspring

-This model is what allows us to do cross-fostering necessary to show that is not about some genetic lineage, but environment

6

like mother, like daughter

-Female offspring that are reared by high licking/ grooming mothers become high licking/grooming mothers when they are adults.

-If moms spends a lot of time LG then her offspring will also spend a lot of time LG their offspring

-Environment is transmitted in a way through this variation in social behavior

-The most important region for maternal behavior is MPOA

7

the transmission of this phenotype is related to methylation of the estrogen receptor alpha gene.

what is the evidence for this

-Looking at female offspring investigators have found that estrogen receptor alpha is regulated in such a way that there is a development pattern of estrogen receptor alpha expression in the MPOA that varies based on that early life environment

-High LG by mom = high levels of estrogen receptor alpha levels in the MPOA

-Low LG by mom = low levels of estrogen receptor alpha levels in the MPOA

8

Why is there higher levels of estrogen receptor alpha levels in the MPOA in female offspring raised by high LG moms?

- Higher levels of estrogen receptor alpha probably stimulate higher levels of maternal behavior in the MPOA

-This difference in expression is likely related to the behavioral phenotype that we see b/c estradiol acts on the MPOA to initiate maternal behavior by driving oxytocin receptor expression

9

limited bedding model method

○ Induces a very aversive state

○ Limit the amount of bedding the mother rat has which prevents her from performing her maternal tasks

-Take away the rats resources

10

limited bedding model is used primarily to study what

to study offspring development as a result of this early life adversity

11

limited bedding results

-Due to the discomfort mother gets very frustrated b/c she cant build a nest properly so she displays neglect and even maltreatment/abusive behavior

-These pups as they get older and develop into adulthood they display
-High anxiety phenotypes
-Poor cognitive control
-Depressive like phenotypes

-Females when they grow up and interact with their offspring are not very good moms

12

T or F: Something about our adult mothering behavior is from when we ourselves are infants

true

13

when looking at maternal behavior in females that experience maltreatment when they were offspring the researchers found that

-when they have their offspring and are given all of the bedding they could need they still display behaviors that are very similar to the kinds of behaviors that their mom displayed towards them in the adverse environment

-They step on their pups
-Show a significant reduction in nursing posture
-Rough handle the pups
-Abusing the pups

14

looking at BDNF in offspring that experience early adversity the results showed that

-In the prefrontal cortex is affected by these early life aversive experiences

-BDNF methylation in prefrontal cortex being altered as a result of these early life adversity

These alterations in BDNF have been linked to a risk for depression and anxiety

-There is an increase in methylation of BDNF in this particular exon and that increased in BDNF is present and seen in adulthood

-The increase is relative offspring that didn’t experience any adversity

-The more methylation of BDNF the less expression of BDNF which plays a role in terms of cognition in prefrontal cortex

15

harlow's work

an early demonstration of how tactile stimulation was important for early life experience

16

Alison Fleming's work

-wanted to understand how early life really extreme deprivation impacts development

-In the artificial reared condition she has a feeding tube, are completely separated from their moms, and are thermally regulated by an incubator and they received LG from a paintbrush

-Offspring that experienced this artificial rearing procedure showed similar problems as the offspring being reared by bad moms and were bad mothers themselves

-offspring are less attentive, more impulsive and poor mothers

17

socioeconomic status affects what

prenatal factors, parental care, cognitive stimulation ---> brain development ----> cognition, academic achievement, mental health

18

SES is associated with adverse adult outcomes

-Increased depression

-Increased anxiety

-Attention problems

-Conduct disorders

-Aggressive or impulsive behavior

- Decreased academic achievement

19

animal model correlate for poor nutrition

Underfeeding/Overfeeding
development

20

animal model correlate for poor parental care

Maternal neglect; exposure to different mothering styles

21

animal model correlate for neighborhood and family

Communal nesting? “Single moms”

22

animal model correlate for exposure to violence

Maternal abuse, Social abuse

23

animal model correlate for material resources and reduced cognitive stimulation

Enrichment versus deprived environment

24

animal model correlate for exposure to toxins

Endocrine-disrupting compound exposure in utero or during postnatal

25

3 stress inducing paradigms

-Maternal deprivation paradigm

-Limited resources paradigm (limited bedding)

-Social defeat paradigm

26

3 ways to measure stress effects

-Social avoidance

-Anhedonia

- Anxiety

27

social defeat paradigm

-Being used as a way of inducing social stress

-Exposed animal to a confrontation

-Take experimental subject and put it into another mice's cage

-Becomes very stressful for both parties, but only one is going to win the fight

- After the confrontation you separate the cage by a glass barrier , so that after they had this very negative social interaction they are sort of threatened by this other animal for the next 24 hrs

- They can smell, see, hear each other but they can’t fight
Is very stressful

28

social interaction test

In the first test (no target), the experimental mouse is allowed to freely explore an arena containing an empty cage. Then the experimental mouse is immediately returned to the arena with a novel mouse enclosed in the plexiglass wire mesh cage. Time spent in the ‘interaction zone’ (light gray) surrounding the plexiglass wire mesh cage, ‘corner zones’ (dark gray), and ‘distance travelled’ within the arena was measured by video tracking software.

-After experiencing something like psychosocial stress, a normally very social animal is going to display social avoidance

-Usually in the normal experiment
○ Animal is put into an empty cage and they are allowed to explore (The mouse investigates and explores )

-Then they are put into the cage but this time with another mouse inside the cage as well but in an enclosed zone
○ Following a psychosocial stress situation, the test animal is very afraid and avoids exploring
Social avoidance is something that we see emerging from psychosocial stress

29

anhedonia

• Anhedonia: things that used to be pleasurable are no longer pleasurable

• Animal is given normal water, then one day they are given sweetened water
○ A normal animal will spend longer time drinking the sweet water than the regular water

-However an animal who no longer feels pleasure from the sweet water will no longer show a preference for the sweet water

30

anxiety

Mice are fearful of wide open spaces and therefore exploration of a novel open field arena is used to assess anxiety.

-animals that have experienced some early life adversity or early stress spend more time around the edges of the arena and less time in the center of the arena

-This behavior is indicative of an anxiety like state