Connecting genes, brain & behaviour: L24

Question 1

Animal models: optogenetics

1. what is used to excite or inhibit neurons by light
2. each responds to light of particular
3. Adeno-associated virus (AVV) is commonly used to

Answer 1

1. microbial opsins
2. wavelength
3. introduce the required genetic material
   - > a cell-specific promotor sequence can restrict opsin expression to particular cell types

Question 2

1. Channelrhodopsin-2 (ChR2) responds to
2. Halorhodopsin (NpHR) responds to
3. light delivered through

Answer 2

1. blue light, depolarisation = neural excitation
2. yellow light, hyperpolarisation = neuronal inhibition
3. implanted optic fibre (stimulates a particular rhodopsin)

Question 3

In combination with an optogentic system, a CRISPR-Cas9 system allows (2)

Answer 3

1. light-controlled protein transcription

2. light-controlled genome editing

Question 4

1. genetic associations with behaviour only
2. using bioinformatics we can translate a human genetic mutation to
3. model organisms allow more direct measurement at multiple levels (3)

Answer 4

1. hint at biological pathways involved
2. target a homologous gene in a model organism
3. (1) structure
   (2) function
   (3) behaviour

Question 5

Imaging genetics

1. HTR1A is
2. if a functional SNP is situated in the promotor region

Answer 5

1. the human gene encoding the serotonin-1A receptor

2. it likely affects protein transcription rather than structure

Question 6

Connecting genes to behaviour

1. the SNP rs6295 in the promotor region of HTR1A is
2. individuals with one or two copies of the G allele showed

Answer 6

1. associated with trait anxiety
2. lower trait anxiety than individuals homozygous for the C allele (dont have a G)

-> G allele fails to suppress the transcriptional activity of the gene -> higher number of serotonin receptors made -> in PEP leads to high serotonin binding (opposite without the G allele)

Question 7

Connecting genes to brain anatomy

1. the HTR1A SNP (rs6295) is associated with
2. additional copies of the G allele were
3. the G allele
4. binding potential is measured using

Answer 7

1. serotonin-binding potential
2. associated with increased binding potential
3. impairs the transcriptional repression of the promoter
   = causes increased expression of the 5-HT 1A receptor (serotonin production)
4. PET
   -> detects radiation from an injected tracer with a high affinity for 5-HT1A receptors
   -> higher density of receptors leads to higher binding potential

-> fewer serotonin 1A receptors = higher amygdala reactivity (hyper reactive) (& opposite)

Question 8

Connecting genes to brain anatomy cont.

1. 5-HT1A receptor is an
2. lower binding potential means
3. transcriptional repression of the promoter causes

Answer 8

1. autoreceptor
   - > located at the presynaptic membrane where it bind neurotransmitters released by the neuron = key part of system for regulating neurotransmitter release
2. lower density of receptors
3. decreased expression of the 5-HT1A

Question 9

connecting brain anatomy to brain function

1. reduced capacity for regulation of 5-HT release is
2. amygdala reactivity was measured by
3. capacity for regulation of 5-HT release was

Answer 9

1. associated with increased amygdala reactivity
2. comparing BOLD activation in the amygdala between two tasks
   - > matching angry or fearful faces vs matching geometric shapes
3. the same PET measure of 5-HT1A binding potential

-> highly active amygdala -> higher trait anxiety
(lower binding potential = higher amygdala reactivity)
negative correlation

Question 10

connecting brain function to behaviour

1. increased amygdala reactivity is associated with
2. amygdala reactivity was measured by comparing

Answer 10

1. increased trait anxiety

2. amygdala BOLD activation when viewing fearful vs neutral faces

Question 11

connecting genes to brain function

1. HTR1A SNP is associated with
2. additional copies of the G allele were associated with

Answer 11

1. amygdala reactivity

2. decreased reactivity

Question 12

connecting brain anatomy to behaviour

1. increased serotonin-binding potential throughout the brain is associated with

Answer 12

1. lower anxiety

Question 13

convergent evidence that:

1. presence of the G allele of rs6295
2. this leads to

Answer 13

1. impairs repression of HTR1A transcription
2. increased receptor density, indexed by binding potential -> leads to decreased amygdala reactivity -> predisposed to low anxiety

Question 14

Conversely:

1. absence of the G allele of rs6295
2. this leads to

Answer 14

1. promotes repression of HTR1A transcription
2. decreased receptor density, indexed by binding potential -> leads to increased amygdala reactivity -> predisposed to high anxiety

Question 15

-> By comparing measurements across multiple levels, we can

Answer 15

-> reveal the likely biological pathway linking a genetic variant to a behavioural phenotype