“Postnatal NMDA receptor ablation in corticolimbic interneurons confers schizophrenia-like phenotypes” is an extremely fascinating article. The article is about postnatal inhibition of NMDAR activity in the corticolimbic GABAergic interneurons in mice causing the mice to have symptoms of schizophrenia. There is NR1 subunit of the NMDAR receptors which was selected for deletion, but not all the NMDAR receptors loss the function of the NR1. Only 40-50% of the NR1 subunit of the NMDAR receptors was deleted in the cortical and hippocampal intereneurons in mice. The reason for the deletion of NR1 is that they are assessing their theory that schizophrenia is not a hyperfunction, but a hypofunction of the interneurons. After deletion of NR1, the behavioral of the mice were assessed. From the assessment, the mice with the early postnatal deletion had impaired spatial memory, social memory, prepulse inhibition and poor nest making skills. The results from the behavior assessment indicate symptoms of schizophrenia. From the outside the mice are experiencing symptoms of schizophrenia, but what is happening on the inside, on the neuronal level; they found out that on the neuronal level the cortical excitatory neurons had a higher mean firing and were unsynchronized. Early postnatal deletion of NR1 in mice results impaired spatial memory, social memory, prepulse inhibition and poor nest making skills due to the increased firing of unsynchronized cortical excitatory neurons.
Personally, the most interesting part of the article is that they tackled the question of age in schizophrenia. Most individuals believe that schizophrenia is a disease that develops later in life. To see if this common belief is true, NR1 deletion was done on adults mice through recombination. The process was started at week 8 mice and completed at week 20 mice. This is where things become interesting when looking at behavior effects of the NR1 deletion in adult mice, they did not experience any impaired spatial memory, social memory, prepulse inhibition and poor nesting making skills. The behavior of the adult NR1 deletion mice indicates that they do not have schizophrenia symptoms or behavior like the early postnatal NR1 deletion mice. However NR1 was deleted, so on the neuronal level the results should be the same as the early postnatal NR1 deleted mice. Oddly enough that is not what happens, it’s the exact opposite. The NR1 deletion in adult mice did lead to the increased firing of unsynchronized cortical excitatory neurons. Well that would make sense because of the NR1 deletion in adult mice did not have schizophrenia symptoms, so their neurons should work fine or normally and that is what is seen in the figure 7. Figure 5 display the results of the NR1 deletion of the early postnatal mice and when comparing these results with figure 7, there is a clear indication that NR1 deletion in adult mice are not experiencing the same neuronal effects as the NR1 early postnatal mice. When comparing both graphs it is clear that schizophrenia is possibly a disease that does not occur in the late age, but in an early age. That statement alone is just mind blowing because it means that the common belief of schizophrenia is incorrect and a question arises whether it is possible to see schizophrenia symptoms in children. If there are signs of schizophrenia then why are they not noticed? Well the symptoms of NR1 deletion of in the early postnatal mice are behaviors of mice who are introvert, they keep to themselves. Some children are like that and they are noticed as being shy. What if being shy is a sign or an indication of possibility that the child can develop full symptoms of schizophrenia in the future. Thinking about this idea lead me to other conclusions, for example many parents allow their children to get away if things that may be inappropriate because children do not know better, but what if they were cues of schizophrenia? At the end of day this experiment was done on mice, so we must not immediately equate the results to humans well maybe it is for me to remember that.
