Connecting Genes, Brain & Behaviour

Question 1

What two things in animals are positively correlated?

Answer 1

Neural complexity and length of life.

Question 2

What aren’t feasible with techniques that rely on breeding multiple generations?

Answer 2

Using more complex species as their lifespans are too long for multiple generations.

Question 3

What are the four steps of forward genetics in animal models?

Answer 3

Mutagenesis, crossing, phenotype, genotype.

Question 4

What happens in mutagenesis?

Answer 4

Inducing mutations, typically use radiation to induce mutations.

Question 5

What happens in crossing?

Answer 5

Cross the mutated animal with one of wild-type strain, over generations some offspring will display some mutations and some will display others or not at all.

Question 6

What happens in phenotype?

Answer 6

Identifying the phenotypes of the offspring.

Question 7

What happens in genotype?

Answer 7

Finding the associated genotype to the phenotype

Question 8

What do they look at in forward genetics?

Answer 8

Anatomy, learning and social behaviour

Question 9

What happens in a reverse genetics approach?

Answer 9

Targeted mutations are introduced and the effect on the phenotype is measured

Question 10

What is the CRISPR-Cas9 system?

Answer 10

A natural part of a bacterium’s defence against invading viruses

Question 11

What can the CRISPR-Cas9 be used to do?

Answer 11

Can be used to create targeted genetic mutations in model organisms

Question 12

What is Cas9?

Answer 12

A nuclease protein (an enzyme that cleaves the chains of nucleotides in nucleic acids into smaller units).

Question 13

What does guide RNA do to the Cas9 protein?

Answer 13

Guide RNA directs the Cas9 protein to the desired DNA sequence, where the Cas9 cuts the DNA

Question 14

What can the random repair process do to the gene?

Answer 14

Can disable the gene, or targeted sequences can be introduced to be inserted during repair

Question 15

What is optogenetics?

Answer 15

Uses microbial opsins to excite or inhibit neurons by light

Question 16

How do neurons respond to light?

Answer 16

Each responds to light of particular wavelengths

Question 17

What is the adeno-associated virus (AAV) commonly used to?

Answer 17

Commonly used to introduce the required genetic material, a cell-specific promotor sequence can restrict opsin expression to particular types

Question 18

What does the channelrhodopsin-2 (ChR2) pump respond to?

Answer 18

Responds to blue light, and allows positive ions into the cell

Question 19

What does the channelrhodopsin-2 (ChR2) pump response result in?

Answer 19

Depolarisation results in neural excitation

Question 20

What does halorhodopsin (NpHR) pump respond to?

Answer 20

Responds to yellow light and allows negative ions into the cell

Question 21

What does the halorhodopsin (NpHR) pump response result in?

Answer 21

Hyperpolarisation results in neuronal inhibition

Question 22

What is light stimulation delivered through?

Answer 22

Light stimulating a particular rhodopsin is delivered though an implanted optic fibre

Question 23

What does stimulating ChR2 in mouse amygdala cells do?

Answer 23

Induces a predatory response

Question 24

What does an optogenetic system in combination with a CRISPR-Cas9 system allow?

Answer 24

Light-controlled protein transcription and light controlled genome editing

Question 25

What can genetic associations with behaviour do?

Answer 25

Can only hint at the biological pathways involved

Question 26

What can we do using bioinformatives?

Answer 26

We can 'translate' a human genetic mutation to target a homologous gene in a model organism

Question 27

What do model organisms allow?

Answer 27

More direct measurement at multiple levels; structure, function, behaviour

Question 28

What is the HTR1A?

Answer 28

It is the human gene encoding the serotonin-1A receptor

Question 29

What can imaging genetics do?

Answer 29

Connects genes, brain anatomy, brain function and behaviour

Question 30

Where is the SNPrs6295 located?

Answer 30

In the promotor region of HTR1A

Question 31

What is the SNPrs6295 associated with?

Answer 31

Trait anxiety

Question 32

How is the SNPrs6295 associated with trait anxiety?

Answer 32

Individuals with one or two copies of the G allele showed lower trait anxiety than individuals homozygous for the C allele

Question 33

What is the SNPrs6295 also associated with?

Answer 33

Serotonin-binding potential

Question 34

How is the SNPrs6295 associated with serotonin-binding potential?

Answer 34

Additional copies of the G allele were associated with increased binding potential

Question 35

What does the G allele do?

Answer 35

Impairs the transcriptional repression of the promotor, causes increased expression of the 5-HT1A receptor

Question 36

How was binding potential measured with PET?

Answer 36

Detects radiation from an injected tracer with a high affinity for 5-HT1A receptors

Question 37

What did binding potential measured with PET find?

Answer 37

Higher density of receptors leads to higher binding potential

Question 38

What is the 5-HT1A receptor?

Answer 38

It is an autoreceptor

Question 39

Why is 5-HT1A an autoreceptor?

Answer 39

It is located at the presynaptic membrane, where it binds neurotransmitters released by the neuron. This is a key part of the system for regulating neurotransmitter release

Question 40

What is reduced capacity for regulation of 5-HT associated with?

Answer 40

Increased amygdala reactivity

Question 41

What was capacity for regulation of 5-HT release the same as?

Answer 41

Same as the PET measure of 5-HT1A binding potential

Question 42

What is increased amygdala reactivity associated with?

Answer 42

Increased trait anxiety

Question 43

What does lower levels of the SNPrs6295 G allele lead to?

Answer 43

Low 5-HT binding potential, high amygdala reactivity, high trait anxiety

Question 44

What does higher levels of the SNPrs6295 G allele lead to?

Answer 44

High 5-HT binding potential, low amygdala reactivity, low trait anxiety

Question 45

What is the HTR1A SNP associated with?

Answer 45

Amygdala reactivity, additional copies of the G allele were associated with decreased reactivity

Question 46

What is increased serotonin-binding potential throughout the brain associated with?

Answer 46

Lower anxiety

Question 47

What is this convergent evidence of?

Answer 47

Presence of the G allele of rs6295 impairs repression of HTR1A transcription, leads to increased receptor density, indexed by binding potential, in turn leads to decreased amygdala reactivity, finally predisposes to low anxiety

Question 48

What happens conversely?

Answer 48

Absence of the G allele of rs6295 promotes repression of HTR1A transcription, leads to decreased receptor density, indexed by binding potential, leads to increased amygdala reactivity, predisposes to high anxiety

Question 49

By comparing measurements across multiple levels what can we reveal?

Answer 49

The likely biological pathway linking a genetic variant to a behavioural phenotype