Skip to main content

Week 6: Modeling Schizophrenia

By
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.

Comments

Post a Comment

Popular posts from this blog

Week 2- Dopamine Modulation of Depressive-like Behaviors

By
The Chaudhury et al paper explored the neural circuit mechanisms involved in the dopamine modulation of certain symptoms of depression. In this study, the researchers looked at social interaction and sucrose preference as part of their social-defeat paradigm, which has been shown in the past to be indicative of depressive-like behaviors. Although I initially did not completely see the connection between the social-defeat stress model of depression and the tonic vs phasic firing of dopamine neurons, it seemed that susceptibility and resilience to stress played a role in the functional/behavioral effects of dopamine firing. It was interesting to see how chronic mild stress with phasic firing of VTA dopamine neurons converted even resilient mice into susceptible mice.  The Tye et al paper similarly looked at the dopamine modulation of depressive-like behaviors, focusing on motivation with the forced swim tests and open field tests, followed by measurement of anhedonia by quantifyi...
Post a Comment
Read more

Sial & Allsop

By
Sial et al. derived a novel approach for studying what they deem vicarious defeat stress (VSDS) as a model for MDD, PTSD, and other mood-related disorders as an alternative to the classical CSDS paradigm. Using adult male mice, they demonstrate that their model induces a robust and measurable social avoidant phenotype as well as other stress and anxiety related behavioral outputs. Their subsequent rescue study with chronic fluoxetine treatment shows reversal of the behavioral phenotypes and emphasizes the predictive validity of the model. Allsop et al. found that BLA-projecting ACC neurons preferentially encode socially derived aversive cue information by encoding the demonstrator’s distress response during observational learning, hence enabling acquisition of negative valence of cue by BLA neurons and behavioral output. In order to test their hypothesis, Allsop et al. used an observational fear conditional paradigm to create association between a conditioned stimulu...
Post a Comment
Read more

Buffington and Reber

By
Buffington et al. explore a mechanism by which maternal obesity can induce neuronal and subsequent behavioral disorders. Using a model of high-fat diet (MHFD)-induced obesity, the authors showcase the strong connection between the brain and the gut, and its impact on behavior. The findings are provocative; by exposing these offspring to the microbiome of control offspring, there was evidence of a rescued observed behavioral phenotype. Furthermore, a phylogenetic profiling of the gut microbiome revealed a decrease in L. reuteri within MHFD offspring, and introduction of live L. reuteri into the drinking water shows successful rescue of the behavioral issues in the MHFD offspring. L. reuteri-induced expression of oxytocin within the paraventricular nuclei of the hypothalamus provides a potential mechanistic explanation for the behavioral changes. I thought this paper provided robust support for the hypothesized interaction between the gut biome and the developing CNS, with tremendous po...
Post a Comment
Read more