Moore et al, a sum of parts.

Obviously when you take parts of a whole it is tough to see the big picture. If you take any of the individual behavioral tests out of Moore’s experimental protocol, they do not make me think of a model of schizophrenia. Most of the deficits noted in the results appear to be symptoms common across psychotic disorders. Modeling schizophrenia is a very complicated task. It is especially difficult to specifically model this disease when there is so much over lap with other psychotic disorders like bipolar, Alzheimer’s, and depression. Moore et al was able to excel at taking a bunch of different symptoms, behavioral and physiological, and showing how they all may be potentially the result of anatomical condensation of neuronal matter in the prefrontal and occipital cortices using MAM.

Moore et al showed that there were anatomical differences, specifically reduction in density of prefrontal cortex, due to MAM treatment. They were then able to show behavioral differences between different groups of cortex makeup. This allowed for the significant results of individual tests like ataxia and prepulse inhibition to be matched to brains with increased density. The timing of MAM treatment is important for the validity of this model moving forward. The treatment says something about how the temporal expression of genes during development may play a key role in schizophrenia.

 In conjunction with the prepulse inhibition, Moore also used PCP for glutamine hypofunction as a means of implicating a dopamine pathway. MAM mice were more responsive to PCP than control. Although there is still a long way to go in developing a perfect model to understand the pathophysiology of schizophrenia, Moore connected a few general psychotic behaviors to some specific anatomical and physiological mechanisms. They showed that broad deficits brought on by the MAM mice are related not only to the increased density of the prefrontal cortex and limbic areas, but also dopaminergic in nature. These two findings set the ground work for more in depth analysis of the circuits underlying the deficits produced by schizophrenia.

One thing that I found myself searching for in the paper, because they talked about it, was the steady number of neurons. I feel that adding a figure on the stereological analysis of the mice would have brought some more clarity. They just stated that the finding was not due to a difference in number of neurons and then went on to provide sufficient figures on the density differences. I think a small figure between 4 and 5, or tacked on to the end of either, would have helped show that it was only a difference in density, not number.