Skip to main content

Week 2: Dopamine circuitry modulation and depression

By
            This week we looked at two similar articles which focused on the neural circuits of the mid-brain, specifically the dopamine neurons in the ventral-tegmental area (VTA) as well as projections to the nucleus accumbens (NAc). The Chaudhury et al. paper investigates how different firing patterns of dopamine neurons (phasic or tonic) with the VTA and NAc regulate depression like behavior. After exposing the mice to 10-day social-defeat stress, Chaudhury found that susceptible (depressed) mice had increased phasic firing, while resilient mice (normal) mice had no changes in firing patterns. Using optogenetics to promote phasic firing, they immediately induce depression like behavior both susceptible and resilient mice, measured in increased social avoidance and decreased sucrose preference. Furthermore, they showed that inhibition of this pathway between the VTA and NAc would immediately induced a resilient phenotype.
The Tye et al. article which aimed to achieve similar goals in identifying the involvement of the dopamine pathway in the VTA and NA in depression phenotypes by exposing mice to 10 weeks of chronic-mild stress (CMS) and using optogenetics to either induce or inhibit firing in this reward pathway. This study found the increased firing of dopamine in the VTA was associated with immediate improvement of depressive phenotypes as shown by increased motor activity exhibited by increased escape behavior in the tail-suspension test (TST) and forced-swim test (FST), as well as improvement of anhedonia modeled by increased sucrose preference. These behaviors were immediately reduced when phasic firing of the dopamine neurons were inhibited, which caused a rapid onset of depressive phenotypes.  
            Upon reading several review articles investigating the comparison of these studies, I learned that all stress is not created equal. Exposure to severe and acute stress for 10 days, as opposed to 10 weeks of CMS, results in different neural changes. While phenotypically the mice may display the same depressive like behaviors of anhedonia, decreased motor activity, and social avoidance, the activity of dopamine neurons in the VTA increases during shot term high stress acuity, while in decreased in a CMS paradigm. These differences in neural circuitry as a result of contextual stress explains the differences between the behavioral outcomes of either excitation or inhibition of midbrain dopamine neurons in mice exposed to stress.
Depression is a complex disorder characterized by a myriad of phenotypes, many of which oppose each other. Clinical outcomes of depression can involve behaviors such as increased or decreased sleep, over or under eating, and heightened or dampened motor movements. Knowing that the cause of stress dictate different neuronal changes, it is conceivable that the phenotypes may not be the same, and therefore the treatments will not be universal. BY further investigating how various causes of stress affect the neural encoding of depression-related behavior, hopefully a more effective and individualized approach to the treatment of depression can be initiated.
           


Comments

Post a Comment

Popular posts from this blog

Gut-Brain Interactions: Buffington et al, Reber et al 2016

By
April 13 Papers (Buffington et. al, Reber et. al) I found this week’s papers to be quite novel in that they both proposed potential treatments for neurodevelopmental or psychiatric disorders that target bacterial or microbial abnormalities and how these give rise to certain behavioral and physical symptoms associated with the disorders. I thought this was a very unusual yet interesting approach, and as I have not previously studied the gut-brain axis, these papers offered me a fresh perspective on researching psychiatric and neurodevelopmental disorders. They were also unconventional in their focus of the physical symptoms that often accompany mental disorders, as this is not something that I have seen many other papers touch upon very much. Particularly, I was surprised by the Reber et al paper’s focus on the link between psychiatric disorders and inflammation in organs other than the brain, such as the colon, and the Buffington et al paper’s description of a relationship between ...
Post a Comment
Read more

Buffington et al. and Reber et al.: Gut-Brain Interactions

By
While I have not encountered a lot of gut-brain interaction literature yet. I found each paper unique and fascinating. Reber et al felt inaccessible for me. I felt like I didn’t understand what the goal of the paper really was and why they did the tests that they did. It seems like most of their relevant information got shoved into numerous supplementary figures and their behavior was quite difficult to follow. Multiple sections of their paper were supported with data found entirely in supplementary figures, which makes it difficult to follow the same conclusions. I have a few issues with the behavior they chose and because of this, I struggle to find driving conclusions from their work. I don’t understand why the CSC was not only the prior stressor but was also the acute stress condition both groups faced. To me, I feel like it would have made more sense to have the CSC be the prior stressor and then judge the effect on social behavior with maybe a three choice chamber test or te...
Post a Comment
Read more

Buffington et al (2016) and Reber et al. (2016)

By
This week's articles were about the role of the gut-brain axis in neurodevelopment and stress. Reber and colleagues used a heat-killed version of the bacteria, M. vaccae, as a type of vaccine and found that administration to mouse models resulted in decreased response to chronic stress, prevented colitis related to stress, and reduced measures of anxiety. Reber et al. also used the inactivated M. vaccae in a mouse model of IBD and found that the bacteria prevented stress-induce flare-ups of colitis, but that this could be reversed by removing T cells. Buffington and colleagues instead examined the role of gut microbiota in maternal high-fat diets (MHFD) in the neurodevelopment and social behaviors of their offspring. Buffington et al. found that housing MHFD rats with the offspring of regular diet (MRD) rats prevented social deficits in their offspring. They also found that this co-housing arrangement prevented an imbalance in the gut bacteria Reber and colleagues' findings w...
Post a Comment
Read more