Science· 2014Q1
Enhancing Depression Mechanisms in Midbrain Dopamine Neurons Achieves Homeostatic Resilience
- 500citations
- Q1SCImago
- 2014year
Short summary
Enhancing the hyperactivity of midbrain dopamine neurons, previously thought to cause depression, completely reversed depression-related behaviors in mice.
AI-generated from the title and abstract; the full text is not read.
Key points
- Depressed mice show hyperactivity of VTA dopamine neurons due to an up-regulated I(h) current.
- Mice resilient to social defeat stress exhibit normal VTA dopamine neuron firing.
- Experimentally enhancing I(h) or VTA dopamine neuron hyperactivity reversed depression behaviors in susceptible mice.
- The reversal of depression behaviors was achieved through resilience-like, projection-specific homeostatic plasticity.
AI-generated from the title and abstract; the full text is not read.
Abstract
Typical therapies try to reverse pathogenic mechanisms. Here, we describe treatment effects achieved by enhancing depression-causing mechanisms in ventral tegmental area (VTA) dopamine (DA) neurons. In a social defeat stress model of depression, depressed (susceptible) mice display hyperactivity of VTA DA neurons, caused by an up-regulated hyperpolarization-activated current (I(h)). Mice resilient to social defeat stress, however, exhibit stable normal firing of these neurons. Unexpectedly, resilient mice had an even larger I(h), which was observed in parallel with increased potassium (K(+)) channel currents. Experimentally further enhancing Ih or optogenetically increasing the hyperactivity of VTA DA neurons in susceptible mice completely reversed depression-related behaviors, an antidepressant effect achieved through resilience-like, projection-specific homeostatic plasticity. These results indicate a potential therapeutic path of promoting natural resilience for depression treatment.
The authors' abstract, as published at the source. Science, 2014 · DOI ↗
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Field: Behavioral Neuroscience
Behavioral NeuroscienceNeuroscience