Kellendonk Paper

Due to the fact that schizophrenia has many different varieties of symptoms associated with it, I find it interesting to see which specific group of symptoms a study is looking at, as well as how they approach the task of creating an animal model for that specific group of symptoms. In the Kellendonk paper, they looked at cognitive symptoms such as impairments in working memory and behavioral flexibility. Specifically, they did this by increasing the amount of dopamine receptors in the striatum, a structure known for its dopamine innervation and role in working memory. 

Overall, I thought that Kellendonk et al did a decent job in organizing the experiments and also in writing about them. Much like the Yiu paper, they were very methodical in documenting their validation of techniques as well as building upon those in each subsequent experiment in a step by step fashion. A couple of other things stood out to me as well.

An over-expression of D2 receptors in the brain is only one hypothesis behind the decreased cognitive functions associated with schizophrenia. Indeed, the Kellendonk team indeed found that increasing the amount of these receptors led to increased difficulties in working memory and behavioral flexibility, but I’m not convinced that this is a major player in the disease. I think that there must be something else going on, either related to other neurotransmitters besides dopamine, or some other genetically-related pathology. I think it will be difficult to look at this disease from a genetics standpoint because it appears to be extremely complex, but from reading this paper as well as the review paper, I would be very interested to read up on the role of GABA in other schizophrenic models.

According to the review paper by Nestler and Hyman, animal models which induce cognitive symptoms are not to be balked at, so this study has that going for it. However, I would have expected the mice in this experiment to show some trace of sensorimotor gating, which was not the case, which I feel tested the validity of their model.