In a recent study, Haijiang Cai, an associate professor in the University of Arizona Department of Neuroscience, and his colleagues were able to map a circuit that gives us better insight into the signaling involved in eating behaviors.
Cai began researching eating behaviors and emotions a bit “by accident.” Now, his lab at the UA is centered around investigating which neurons and neurocircuitry patterns are involved in eating behaviors and emotions.
Relatively little is known about the neurocircuitry involved in eating behaviors and how it connects to the neurocircuitry involved in emotions. According to Cai, we know that the two functions have an intimate relationship because people that struggle with eating behaviors also often struggle with emotional problems.
For example, he explained that patients with anorexia nervosa also typically have anxiety or depression. In fact, according to Tiffany Cho, an undergraduate researcher on the project, emotion management is actually the primary treatment for anorexia nervosa.
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Cai also noted that it is highly unlikely that each of these functions is controlled by just a single brain region. So, while we know that these functions are intimately linked, scientists do not yet know the specifics about how neural circuits that correspond to each function relate to and differentiate from one another.
Prior to this study, it was known that a neural pathway involving populations of neurons in the amygdala played a role in cholecystokinin, or “CCK.” CCK is a neuropeptide that sends signals from the gut to the brain which tell the brain “I’m getting full.” They knew that a population of neurons in the amygdala began a signaling pathway, but where the signal went next was unknown. Cai and his team were able to map the downstream effects of this circuit, or where the signal goes next.
According to their research, after passing through the amygdala, the signal goes to a region of the brain called the parasubthalamic nucleus, or the PSTh. The PSTh was already thought to be a “communication point for feeding behavior,” according to Cho, but these researchers were able to pinpoint more specifically what role the PSTh has in the chain of events that leads to an eating behavior.
Using mice subjects, the researchers found that when they incited higher activation in a group of neurons in the amygdala called PKC-δ+ neurons, the downstream effect was higher activation in PSTh neurons. When there was more activity in PSTh neurons, the mice ate less. Here is how the circuit actually works.
When PKC-δ+ neurons in the amygdala are activated, these neurons inhibit the effects of PKC-δ- neurons in the amygdala. PKC-δ- neurons normally inhibit neurons in the PSTh, but when they are being limited by PKC-δ+ neurons, they have less of an inhibitory effect. So, there is more activity in neurons in the PSTh, which ultimately leads to feeding suppression in the mice, or not eating as much. According to Cho, we can think about it in terms of a metaphor involving three parties: you, your parents and your controlling boyfriend.
In this scenario, your parents are the PKC-δ+ neurons, your controlling boyfriend is the PKC-δ- neurons and you are the PSTh neurons. Without the activation of your parents, your controlling boyfriend can limit or inhibit your freedom. But, when your parents intervene and prevent the boyfriend from exerting control over you, you have more freedom and can do more activities. In this context, when you as the PSTh neurons can be more active, this manifests in the behavior change of eating less.
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Cai identified an important implication that this research could have in the future. He explained that there are only six FDA approved drugs for weight management treatment. These drugs are formulated to target specific neurotransmitters, which can be found all across the brain. In other words, Cai said each drug “functions on many brain regions,” and causes a myriad of side effects. Cho said this similar to the impact of selective serotonin reuptake inhibitors or SSRIs, a common class of drugs used to treat depression. These drugs also tend to have a wide range of side effects for the same reason.
Cai said that if they can continue to pinpoint these very specific neural circuits that correspond to very specific behaviors, scientists can ultimately formulate drugs that target the problem more accurately and cause fewer effects.
According to Cai, the next step in this research is to find if the same neural mechanism exists in humans. He also discussed the future of weight management drugs if research like his continues, saying, “If we can directly target these feeding specific neural circuits, then we can create drugs that just target appetite for body weight.” The hope is that someday, scientists can create weight management drugs that don’t have side effects.
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While this discovery alone does not give scientists enough information to take a major step in improving weight management and eating disorder treatments, Cho explained that it does give them one more piece of the puzzle – the eating behavior neurocircuitry puzzle, that is.
This finding is a piece of groundwork which, when connected with other pieces of groundwork, will eventually allow us to understand how the brain works on a more intricate level and help us gain insight into the signaling involved in emotions and eating behaviors.
Cho also mentioned that this research is an important reminder that “we can always dive deeper,” and that “there is always more to learn.”
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