The two articles by Tye et al. and Chaudhury et al. each examined the impacts of optogenetic stimulation in VTA dopaminergic neurons in depressive-like behaviors. They each aimed to delineate the downstream effects of VTA dopaminergic neuron firing, but came to differing conclusions.
Tye and colleagues found that inhibiting phasic firing in VTA dopaminergic neurons induced depression-like behaviors in healthy mice. Additionally, they found that inhibiting projections from the VTA dopamine neurons to the NAc increased depression-like behaviors.
Chaudhury and colleagues found basically the opposite: that an increase in phasic firing of VTA dopaminergic neurons induced depression-like behaviors, and inhibiting projections from the VTA dopaminergic neurons to the NAc improved depressive behaviors.
I find it kind of ironic that two studies in complete disagreement were published in the same journal, at the same time. While the two used similar methods to investigate their hypotheses (optogenetics and behavioral tests), they had an overwhelming number of stark differences. First, Tye et al. used both transgenic mice and rats for different parts of their studies, while Chaudhury and colleagues used mice for all of the components of their research. As Tye and colleagues mentioned in their conclusions, this is a potential reason for discrepancies in their findings, because the neural circuitry and behavior outcomes are not identical between species. I think this also warrants further thought, as the difference between rodent brains and human brains is even greater.
Another difference between the research methods of Tye et al. and Chaudhury et al. is their use of behavioral paradigms to assess depression-like behaviors. Tye and colleagues used the chronic mild stress (CMS) paradigm to put rodents a depressive like state. CMS is a well-validated method for inducing depressive behaviors in mice and rats, which was their reasoning behind using it. Chaudhury and colleagues instead used social-defeat stress to achieve the same goal. Because of the differences between CMS and social defeat, Tye et al. and Chaudhury et al. also used different behavioral tests to assess the behavioral symptoms of depression in their respective rodent models. Tye et al. used tests that assessed decreased motivation (tail suspension test, forced swim test) and anhedonia (sucrose preference test) — two symptoms of depression in humans. Chaudhury and colleagues also used the sucrose preference test to test anhedonia, but they used the social interaction test to measure changes in social preferences. The use of different measures of depression-like behavior could be one explanation for the contrasting results between Tye et al. and Chaudhury et al. However, it is important to note that neither study truly examined depression-like symptoms in a comprehensive way, or in a way that is truly comparable to depression in humans. This is always a limitation of animal models of human mood disorders, though.
Overall, I feel that Chaudhury and colleagues' study was more extensive in comparison to Tye et al., but the fact that they used only two measures of depression-like behavior is concerning and leads me to the conclusion that neither of the two studies can be taken too seriously. Additional work in this area is necessary before any strong claims can be made.
Tye and colleagues found that inhibiting phasic firing in VTA dopaminergic neurons induced depression-like behaviors in healthy mice. Additionally, they found that inhibiting projections from the VTA dopamine neurons to the NAc increased depression-like behaviors.
Chaudhury and colleagues found basically the opposite: that an increase in phasic firing of VTA dopaminergic neurons induced depression-like behaviors, and inhibiting projections from the VTA dopaminergic neurons to the NAc improved depressive behaviors.
I find it kind of ironic that two studies in complete disagreement were published in the same journal, at the same time. While the two used similar methods to investigate their hypotheses (optogenetics and behavioral tests), they had an overwhelming number of stark differences. First, Tye et al. used both transgenic mice and rats for different parts of their studies, while Chaudhury and colleagues used mice for all of the components of their research. As Tye and colleagues mentioned in their conclusions, this is a potential reason for discrepancies in their findings, because the neural circuitry and behavior outcomes are not identical between species. I think this also warrants further thought, as the difference between rodent brains and human brains is even greater.
Another difference between the research methods of Tye et al. and Chaudhury et al. is their use of behavioral paradigms to assess depression-like behaviors. Tye and colleagues used the chronic mild stress (CMS) paradigm to put rodents a depressive like state. CMS is a well-validated method for inducing depressive behaviors in mice and rats, which was their reasoning behind using it. Chaudhury and colleagues instead used social-defeat stress to achieve the same goal. Because of the differences between CMS and social defeat, Tye et al. and Chaudhury et al. also used different behavioral tests to assess the behavioral symptoms of depression in their respective rodent models. Tye et al. used tests that assessed decreased motivation (tail suspension test, forced swim test) and anhedonia (sucrose preference test) — two symptoms of depression in humans. Chaudhury and colleagues also used the sucrose preference test to test anhedonia, but they used the social interaction test to measure changes in social preferences. The use of different measures of depression-like behavior could be one explanation for the contrasting results between Tye et al. and Chaudhury et al. However, it is important to note that neither study truly examined depression-like symptoms in a comprehensive way, or in a way that is truly comparable to depression in humans. This is always a limitation of animal models of human mood disorders, though.
Overall, I feel that Chaudhury and colleagues' study was more extensive in comparison to Tye et al., but the fact that they used only two measures of depression-like behavior is concerning and leads me to the conclusion that neither of the two studies can be taken too seriously. Additional work in this area is necessary before any strong claims can be made.
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