Week 6

Both of this week’s papers addressed the pathology of schizophrenia. I have never read papers about schizophrenia before, so these papers were particularly interesting, especially because schizophrenia is such a fascinating and complicated disease. The two papers tackled different aspects of schizophrenia's complex pathology; Moore et. al administered a methylating agent to embryonic mice and discussed resulting cerebral cortical development and schizophrenic-like symptoms, while Kellendonk et. al focused on the dysregulation of D2 receptors implicated in this pathogenesis. I first read Moore et. al’s paper and found this to be a convincing presentation of the MAM model in creating schizophrenic symptoms. I also enjoyed reading about the various behavioral tests (orofacial dyskinesia, reversal learning, locomotor responses, etc.) that are used to verify cognitive and motor deficits seen in schizophrenia; the inclusion of these various tests absolutely strengthens their findings. For the most part, I found the Moore paper to be comprehensible despite my lack of background knowledge regarding schizophrenia animal models; however, I was confused about the prepulse inhibition test and exactly how this test is conducted. I also had questions regarding the use of amphetamine as a test for locomotor response and how the use of this drug is relevant as a behavioral test for schizophrenia.

Regarding the Kellendonk et. al paper, I was most confused about the finding regarding the D1 receptors’ involvement in overactive D2 receptor activation and subsequent working memory deficits. I found this paper easy to follow until Figure 6 when D1 receptors were introduced; this may be due to a lack of understanding regarding the circuits involved and the specific receptor properties of D1 and D2. Regardless, I found it to be difficult to make sense this finding, and I'm hoping we elaborate on this particular figure in class.

Finally, I did notice both of these papers were published in 2006; it would be interesting to see how dramatically subsequent research has elaborated on these findings since these publications.