PSYC20006 Lecture Notes - Lecture 15: 5-Ht1A Receptor, Forward Genetics, 5-Ht Receptor
12 Jun 2018
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Lecture 15 - Thursday 27 April 2017
PSYC20006 - BIOLOGICAL PSYCHOLOGY
LECTURE 15
CONNECTING GENES, BRAIN & BEHAVIOUR
TODAY
•From genes, to brain, to behaviour
•Imaging genetics
•Animal models
•Forward genetics
•Reverse genetics
FROM GENES, TO BRAIN, TO
BEHAVIOUR
•How do we go about tracing the
biological cascade chain in an empirical
and evidence based way to truly
understand how we get from a change in
a gene to a change in a behaviour?
•HTR1A gene: associated with trait
anxiety and tendency over time to be
susceptible to anxiety.
•HTR1A is the human gene that encodes
for the serotonin 1A receptor. Has a role
in mediating inhibitory neurotransmission.
When this kind of transmission occurs, it
inhibits the activity of other cells. The
protein is encoded by the gene HTR1A on the
long arm of chromosome 5. There is an
encoding region that has the base that instruct
where the amino acids need to go to construct
the protein. The snip we are looking at here is
in the promoter region. The snip is called8
r6s295. The two alleles of the snip are the C
and the G allele, so we can have CC or CG or
GG.
•What we are dealing with is a marker that
looks like it is involved in regulation of the
transcription of the gene and not differences in
the gene itself.
•The graph below is from a paper by Fakra et
al. Says that individual without the G allele have a higher propensity
for trait anxiety than those with the allele. This assumes an
autosomal gene, it could be either dominant or recessive, depends on
how we define the trait. If we define it as high trait anxiety, we need
both copies of the C allele, if it is low trait anxiety then any copy of
the G allele puts you in this category.
•Note there is no clear direction of effect here (low or high), then
the dominant/recessive can switch around.
•How do we get from the gene to the behaviour?
•A pet study. What happens here is we inject a radioactive molecule
with an affinity for a particular substance in the body that will bind
to it and we can look at the concentration of that molecule in the !
Lecture 15 - Thursday 27 April 2017
PSYC20006 - BIOLOGICAL PSYCHOLOGY
!
body/brain.
•Can work out the concentration
based on how much of the molecule
has bound to the receptor.
•They looked in the hippocampus and
in the R something nuclei (RN). More
copies of the G allele would have a
higher binding potential, shown by
more binding to receptors. This is an
allelic dosage model. Each additional copy of the
micro-allele increases the dosage.
•So the G allele is impairing the transcriptional
oppression of the promoter region. The G allele
inhibits this, so the molecule is being over
expressed.
•Seems to be specific to autoreceptors; receptors
that sit on the same cell that releases the NT.
Basically they monitor how much NT is produced/
released.
GENES TO BRAIN
•In this study we have the same PET
measure of serotonin receptor density, but
we also have a fMRI measure.
•We are particularly interested in the
bilateral amygdala.
•The fMRI measure of amygdala reactivity; matching angry
and fearful faces/matching geometric shapes.
•If you plot each subject’s binding potential against their
reactivity, you get a nice strong negative relationship.
•About 44% of variance shared between the two measures.
•The reduced capacity for regulation of the serotonin
pathway is associated with increased amygdala reactivity. This
is the link between the brain anatomy and the brain function.
•The last step is the last study. Measures amygdala reactivity
slightly differently but still with faces (difference is trivial).
Looking at relationship between fMRI amygdala measure and
the original phenotype, trait
anxiety. It is plotted against
each other in
the bottom
right corner:
•High
reactivity is
predictive of!
!
