Summary of When These Neurons Are Activated by Chronic Stress – Behavioral Problems Like Depression and PTSD Result:
Chronic stress leads to hyperactivity in a group of neurons called POMC neurons, located in the hypothalamus region of the brain, which can result in behavioral problems such as depression, anhedonia, and PTSD. Scientists at the Medical College of Georgia at Augusta University found that inhibiting the firing of these neurons reduced stress-induced behavioral changes in mice. The study indicates that POMC neurons are necessary and sufficient to increase susceptibility to stress, and their increased firing is a driver of resulting behavioral changes. The study also suggests that opening potassium channels, which are known to decrease excessive firing, may be a possible targeted treatment for restraining the wildly firing POMC neurons in response to chronic stress.
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Introduction
Have you ever experienced a prolonged sense of stress that left you feeling emotionally drained? If you have, then you know that it can lead to behavioral problems like depression, anhedonia, and even post-traumatic stress disorder (PTSD). While the effects of chronic stress on our behavior are well-known, the mechanisms behind them have been somewhat of a mystery until now. New research published in the journal Molecular Psychiatry has uncovered a group of neurons, located in the hypothalamus, which become hyperactive in response to chronic stress, causing these behavioral issues.
The Proopiomelanocortin Neurons
Scientists at the Medical College of Georgia at Augusta University discovered that chronic, unpredictable stress increased the firing of proopiomelanocortin (POMC) neurons in male and female mice. Located in the arcuate nucleus of the hypothalamus, the POMC neurons are responsible for releasing hormones and regulating hunger, thirst, mood, sex drive, and sleep. When the POMC neurons become hyperactive, it results in the inability to feel pleasure, referred to as anhedonia. In mice, this can be seen when they stop displaying a love for sugar water or a decreased interest in the urine of females when they are in heat.
Decreasing POMC Neuron Activity
When scientists inhibited the firing of the POMC neurons, it reduced stress-induced behavior changes in both male and female mice. These results indicate that POMC neurons are “both necessary and sufficient” to increase susceptibility to stress and that their increased firing is a driver of resulting behavioral changes like depression. Stress also decreases inhibitory inputs onto POMC neurons, making their activity even more intense.
The Yin-Yang Relationship
POMC neurons have a yin-yang relationship with agouti-related protein (AgRP) neurons. When AgRP activation goes up, POMC activation goes down. Chronic stress disrupts this balance and leads to an overactive POMC population. While AgRP neuron activation is essential for the inhibition of POMC neuron firing activity, the intrinsic mechanism is likely responsible for most of the hyperactivity observed in POMC neurons due to chronic stress. This intrinsic mechanism may include potassium channels in POMC neurons that respond to a range of different signals. When the channels are open, potassium flows out of the cell, lowering neuronal excitation. However, stress affects potassium channels and opening those channels may be a possible targeted treatment to restrain the excessively firing POMC neurons.
Clinical Applications
Excessive activity of neurons can produce seizures, and anticonvulsants may reduce excessive firing by opening potassium channels. Recent clinical evidence suggests that these drugs may treat depression and anhedonia. The findings of the Lu lab may explain why. Continued research into the role of potassium channels in POMC neurons may lead to targeted treatments for people experiencing chronic stress.
Conclusion
The role of POMC neurons in chronic stress-induced behavioral changes has been discovered. Increased firing of these neurons leads to depression, anhedonia, and PTSD-like behaviors. Decreasing their activity has been shown to alleviate these issues. Research into the mechanisms behind this increased activity may lead to targeted treatments that can help people dealing with chronic stress regain their emotional wellbeing.
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