Much like the articles from our first class discussion, Tye et al. and Chaudhury et al. report on studies with similar focuses and end with different but complementary conclusions. Both papers introduce the concept that dopamine neurons in the brain’s reward circuit play a crucial role in the underpinnings of stress-induced depression-like phenotypes. Both studies also choose to investigate this claim through the use of optogenetics and the excitation or inhibition of neuronal pathways from the ventral tegmental area (VTA). Chaudhury et al. looks at these projections to the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) while Tye et al. looks only to the NAc.
A primary difference in the experiments are the stress paradigms utilized and the behavioral measures assessed afterward. Tye et al. employed the chronic mild stress (CMS) paradigm which has previously been shown to produce decreases in motivation as well as anhedonia. Similar results were found here with effects reversed by excitation through channelrhodopsin (ChR2) blue light stimulation. CMS animals exposed to the tail suspension test had markedly reduced amounts of escape-related behavior (a measure of motivation) compared to controls with a robust increase in ChR2-CMS animals. Likewise, CMS mice expressed lower sucrose preference (a measure of anhedonia) while the effects were reversed in the ChR2-CMS group. Interestingly, otherwise normal mice whose VTA neurons were inhibited through halorhodopsin (eNpHR) showed similar characteristics to CMS control mice. This shows a bidirectional effect of dopamine neuron activity that can induce or ameliorate depression-related behaviors.
On the other hand, Chaudhury et al. examined the effect of ChR2 excitation on mice undergoing subthreshold exposure to social defeat. Less social interaction and less sucrose preference defined the “susceptible” phenotype of mice who were exposed to the social defeat paradigm while normal social interaction and sucrose preference were part of the “resilient” phenotype. The experimenters concluded that phasic (not tonic) stimulation of the VTA instantly induced the susceptible phenotype. While Chaudhury et al. describes it as a fairly direct link between dopamine firing and susceptibility to depressive-like behavior, they also note that the effects are highly complex and dependent on context and stress severity.
Overall, while it seems as though Tye et al. found the depressive phenotype through eNpHR inhibition and Chaudhury et al. found it through ChR2 excitation, the stress paradigms and the actual viruses used were not identical. I didn’t fully grasp all the differences between them in order to hypothesize how it might have affected the results, but there always exists a possibility that notable differences like those could be a primary influencer on final conclusions. Ultimately, while some of the findings are useful to further confirm what we know about dopamine pathways, we should have a healthy bit of skepticism when comparing the results side by side.
A primary difference in the experiments are the stress paradigms utilized and the behavioral measures assessed afterward. Tye et al. employed the chronic mild stress (CMS) paradigm which has previously been shown to produce decreases in motivation as well as anhedonia. Similar results were found here with effects reversed by excitation through channelrhodopsin (ChR2) blue light stimulation. CMS animals exposed to the tail suspension test had markedly reduced amounts of escape-related behavior (a measure of motivation) compared to controls with a robust increase in ChR2-CMS animals. Likewise, CMS mice expressed lower sucrose preference (a measure of anhedonia) while the effects were reversed in the ChR2-CMS group. Interestingly, otherwise normal mice whose VTA neurons were inhibited through halorhodopsin (eNpHR) showed similar characteristics to CMS control mice. This shows a bidirectional effect of dopamine neuron activity that can induce or ameliorate depression-related behaviors.
On the other hand, Chaudhury et al. examined the effect of ChR2 excitation on mice undergoing subthreshold exposure to social defeat. Less social interaction and less sucrose preference defined the “susceptible” phenotype of mice who were exposed to the social defeat paradigm while normal social interaction and sucrose preference were part of the “resilient” phenotype. The experimenters concluded that phasic (not tonic) stimulation of the VTA instantly induced the susceptible phenotype. While Chaudhury et al. describes it as a fairly direct link between dopamine firing and susceptibility to depressive-like behavior, they also note that the effects are highly complex and dependent on context and stress severity.
Overall, while it seems as though Tye et al. found the depressive phenotype through eNpHR inhibition and Chaudhury et al. found it through ChR2 excitation, the stress paradigms and the actual viruses used were not identical. I didn’t fully grasp all the differences between them in order to hypothesize how it might have affected the results, but there always exists a possibility that notable differences like those could be a primary influencer on final conclusions. Ultimately, while some of the findings are useful to further confirm what we know about dopamine pathways, we should have a healthy bit of skepticism when comparing the results side by side.
Comments
Post a Comment