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Week 6: Modeling Schizophrenia

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Ayhan et al and Burrows et al made me consider runaway excitation in a non-seizure disorder setting. In the last lab I worked in, we worked exclusively with Interneurons, but specifically seizures disorders that result from dysfunctional sodium channels in PV+ interneurons. This haploinsufficiency would result in epilepsy. In the lab we often talked about the implications our research could have on other mental disorders like schizophrenia. I’d be curious to utilize the Ayhan animal tet-off system in combination with studying the electrophysiological properties of interneurons. While they were able to show a decrease in the amount of PV+ cells in the cortex, I’d be curious to see how the function of the neurons changes at various developmental stages with exposure to hDISC1. In this model, it could be possible that function is not altered in this system or what few PV cells remain could also be insufficient to inhibits the proper cells and lead to runaway excitation that leads to hyperactivity and hallucinations. The Burrows paper focused more so on the effect of EE in an animal lacking mGlu5 and considering the role of NMDARs in schizophrenia. Given that there is a school of thought that interneurons facilitate synaptic remodeling and other plastic changes in cells in fear learning circuits, I’m wondering if the plasticity in a normal WT mouse is modulated by these interneurons and in a schizophrenic model the deficiency of interneurons results in “improper” plastic regulation. Similar to what Beth Stevens lab found with the role of glial cells in the synaptic pruning process in schizophrenia, it could be possible that interneurons also play a role in plastic changes in cells and in a model where these cells are defective or insufficient, then it could be a possible link to certain behavioral stereotypes seen in this disorder. I’d be really interested to utilize these mouse models while manipulating interneurons activity to see if there could be any sort of behavioral rescue or varied changes in neuronal morphology. Working with a strong focus on interneurons has constantly made me consider the role microcircuits play in behavior and the active role inhibition can play in modulation Glutamatergic activity.

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