Mechanisms of brain function

Question 0

what did hebb say about synaptic plasticity in 1949?

Answer 0

increases in synaptic strength are governed by coincidence of pre and post synaptic activity - neurons firing together causes these connections between these neurons to be strengthened
- therefore when 1 becomes active it is more likely to set off the other

Question 1

what did cajal say about synaptic plasticity in 1890?

Answer 1

the efficacy of connections between brain cells might be physical of memory

Question 2

what did bliss and lomo say about synaptic plasticity in 1973 ?

Answer 2

discovery of activity dependent synaptic enhancement - if you stimulate neurons in the hippocampus you can strengthen their output
- they first showed long term potentiation

Question 3

why can we remember stuff ?

Answer 3

because connections within the brain have been influenced by the event - this enables us to recall it
- recall memories due to biochemical changes in the brain

Question 4

what does anisomycin do ?

Answer 4

inhibits protein synthesis

Question 5

what does actinomycin D do ?

Answer 5

inhibits RNA synthesis

Question 6

what makes us think that RNA and protein synthesis are important in synaptic plasticity ?

Answer 6

when a high frequency stimulation is applied it causes an increase in the post synaptic response- it is this which is thought to be the underlying mechanism of memory

• the initial phase of long term potentiation requires protein synthesis- we know this because when it is inhibited the increased repsonse from the HFS gradually returns to baseline when the stimulation stops
• the latter phase of long term potentiation requires new RNA synthesis- we know this because the enhanced response remained for a while while protein synthesis occurred but then the activity declined

Question 7

what technique recently proved that long term potentiation underlies memory ?

Answer 7

optogenetics

Question 8

why cant protein to RNA occur endogenously ?

Answer 8

because there is no enzyme to convert the amino acid sequence to nucleic acids
- this cannot occur because the amino acid code is degenerate

Question 9

what are the different control points to control the central dogma ?

Answer 9

• transcriptional control
• RNA processing control
• RNA transport and localization control
• translational control
• mRNA degradation control
• protein activity control

Question 10

why is transciptional control very important ?

Answer 10

because if there is no RNA then no protein can be made

Question 11

where can RNAs be targeted to ?

Answer 11

cytosol but also synapses

Question 12

once a protein is made how can it be controlled ?

Answer 12

controlled by post translational modifications or degradation or cause it to stay around longer

Question 13

what are transcription factors ?

Answer 13

proteins that bind DNA and regulate transcription

Question 14

what are the types of transcription factors and what do they do ?

Answer 14

repressor- can reduce activity of RNA polymerase or reduce likelihood of a complex forming
enhancer- enhance transcription by increasing activity of RNA polymerase to enhance amounts of mRNA

Question 15

what does every gene have ?

Answer 15

a promoter

Question 16

what does a promoter do ?

Answer 16

a DNA region which determines where, when and at what level a gene is expressed

Question 17

what is the basal promoter and how long is it ?

Answer 17

factors for all genes are recruited here

it is 200bp long

Question 18

what factors are present in the basal promoter region ?

Answer 18

TATA box- interacts specifically with TATA binding protein - this is not present in all genes
CAT box- this can recruit different transcription factors including C/EBP, CBF, NF1 - it can recruit anyone of these factors and it will recruit different ones at different times

Question 19

what is the first stage of the transcription process?

Answer 19

TF11D binds to TATA which is a complex of proteins including TBP
when TF11D binds it also brings aloong TF11A
this process causes bending of the DNA which is important because it enhances the recruitment of other factors

Question 20

what is the 2nd stage in the transcription process ?

Answer 20

TF11D recruits TF11B

Question 21

what is the 3rd stage of the transcription process?

Answer 21

TF11B then recruits RNA polymerase 11 and TF11F

Question 22

what is the 4th stage of the transcription process?

Answer 22

TF11E and TF11H come along to phosphorylate RNA polymerase which tells RNA polymerase to start transcription

transcription is initiated

Question 23

what do the basal transcriptional complexes enable ?

Answer 23

they only cause a low rate of transcription
- these factors are essential for the initiation of transcription but it requires enhancers= transcription factors to stimulate the basal rate of transcription

Question 24

what do transcription factors determine ?

Answer 24

they determine the expression and the level of expression of a gene in a cell

Question 25

what do you see in an electron migraph showing gene transcription ?

Answer 25

it creates a branching christmas tree effect with RNAs coming off the DNA strand because multiple RNA polymerases can transcribe a gene at the same time

Question 26

what is a property of enhancer/repressor transcription factors in the position on DNA ?

Answer 26

they are position and orientation independent

• they can bind on the top or bottom of DNA
• to initiate transcription they are found at the 5’ end of the DNA but they can be many base pairs from the start site
• they have also been bound in introns
• they bind to 3’ end after transcription

Question 27

what does CREB stand for ?

Answer 27

cAMP responsive element binding protein

Question 28

what happens when a transcription factor which has positive effects binds to CREB ?

Answer 28

it will enhance transcription
if you get multiple transcription factors it will enhance transcription in different ways they will work in a synergistic way

Question 29

what happens when different transcription factors work together in a synergistic way ?

Answer 29

if one of the transcription factors causes a 3 fold increase in transcription and the other transcription factor also causes a 3 fold increase then it will cause a 9 fold increase all together
- therefore you dont need many transcription factors and they dont need to work that well to cause a significant increase

Question 30

what did a mutation in a drosphilia fly cause ?

Answer 30

it caused a mutation in the genes causing enhancement in the genes producing attenae so it caused the production of extra legs insted- it was a mutation in homeotic gene

Question 31

what is recent technique has been developed to produce neuronal cells to carry out experiments on ?

Answer 31

converting already differentiated cells such as fibroblasts and converting them to embryonic stems which you can then convert into any type of cell that you want
- it is the production of induced pluripotent stem cells

Question 32

what is a major issue of converting fibroblasts to neurons and then injecting them into a mammal?

Answer 32

if any of the stem cells are not completely differentiated then they can give rise to a tumour

Question 33

why are genes not all expressed at the same level ?

Answer 33

because transcription factors control the level of expression and it depends how much a gene needs to be expressed
– there is a correlation between RNA levels and protein levels but there are exceptions

Question 34

what signals can cause changes in the level of gene expression ?

Answer 34

coupling of G proteins to GPCRss
stimulation of adenylate Cyclase
stimulation of cAMP activity
stimulation of PLC