Much of the research within the Behavioural Neurogenetics
group focusses around investigating how genetic and/or environmental factors
shape our brain and behaviour. With respect to the genetic factor, we are
fortunate to have several genetic models in our group that we developed over
the years. One of these is the serotonin transporter knock-out rat (SERT KO).
The SERT is a protein that is specifically involved in the removal of serotonin
(5—hydroxytryptamine, 5-HT) from the extracellular space back into the neurons.
Thus, a reduction in SERT activity will lead to an increase in extracellular
5-HT. Importantly, many genetic studies in humans have found that a genetic
reduction in SERT activity enhances the risk for different psychiatric
disorders, such as major depression, anxiety disorders, autism spectrum
disorder and drug addiction. Unfortunately, it is very difficult to assess from
studies in humans whether a genetic change is causally linked to a disorder, as
individuals often have multiple other genetic changes as well. Moreover, we
know that environmental factors interact with genetic components, and of course
people have different life histories. With animal research, on the other hand, we
can ensure a similar genetic and environmental background thus allowing us to
investigate the causality between genetic factor and behavioural/brain changes.
We have several different projects comparing normal
(so-called wildtype, WT) rats with both heterozygous (SET HET) and homozygous
(SERT HOM) knock-out rats. The SERT HET rats have about 50% of the SERT
proteins compared to the WT, which is a similar reduction to that seen in
humans with the genetic alteration in the SERT. The SERT HOM rats, on the other
hand, have no SERT proteins at all. While this has not been observed in humans,
it is often useful to investigate both SERT HET and SET HOM rats to see whether
the effects get more intense with fewer SERT molecules (i.e. a so-called
gene-dose effect).