Deconstruction of a Neural Circuit for Hunger, Essay Example

The main purpose of the study was to reveal the morphological and functional basis in central nervous system responsible for feeding behavior. The research is targeting AGRP neurons and their connection to other brain structures. Interactions mapping was performed to indicate morphological structures involved in responding to AGRP neurons’ stimuli. It was stated that AGRP neurons interacted with the main brain structures: paraventricular hypothalamus responsible for oxytocin production, POMS neurons and PBN responsible for visceral malaise. Thus, functional relations between these structures were studied in this research. All in all, the entire study was conducted to undercover the behavioral responses to activation of certain structures, interaction between the structures, and the possibility of influencing the structures to control hunger and feeding behavior. Pharmacological influences were also discovered in this study.

Figure 1 represents the study of ARC^AGRP and ARC^POMC interaction. This part of the study was conducted in order to research the connection between these groups of neurons and their role in evoked feeding. They had to investigate if AGRP neurons stimulating could provoke acute hunger through influencing POMC neurons. If we take a look at sub-figures 1h-j we will see that no immediate response was registered before photostimulation of the structures. On sub-figure 1h we can see the scheme of laser influence on both AGRP and POMC neurons with changing of their membrane current, which indicates that only the release of ARC^AGRP to ARC^POMC connection by suppressing its inhibition with photostimulation may lead to the immediate potential response. Otherwise, as stated in the article, this connection is not responsible for acute hunger, but plays an important role in long-term feeding behavior by increasing food consumption. Sub-figure 1i and 1j demonstrate the same as 1h, but from the behavioral point of view. Sub-figure 1i indicates the consumed amount of pellets with no external stimulus for the first hour and 1-hour photostimulation, which shows the significant increasing of the number of pellets during and after the laser influence. We could also assume that stimulation of this interaction leads to long-lasting feeding behavior changes as the curve indicating the amount of pellets does not go down after the influence of laser was stopped. Meanwhile, sub-figure 1j shows food consumption before, during and after the stimulation and reflects approximately the same, as 1i. It shows that photostimulation increases hunger and feeding while laser influence, after the stimulus is released food consumption goes down, but does not return to the previous amount. These results demonstrate that energy insufficiency does not lead to the immediate activation of ARC^AGRP to ARC^POMC conduction and does not cause evoked feeding, but regular stimulation of it may influence long-term feeding behavior.

Figure 2 shows the influence of both PVH and PBN onto the feeding behavior. The study was conducted because it was never clarified if AGRP neurons target PVH directly, as the influence to it could be mediated by influence of AGRP onto different areas of brain, that could influence PVH afterwards and cause changing to feeding behavior. Although it was shown by mapping that AGRP neurons have their axons extended to PVH area, that would be useful to research. Sub-figures 2a and 2c represent the model of the experiment performed to indicate the roles of PVH and PBN in feeding behavior. On the figure we can see that ARC axons are connected to both PVH and PBN, which was found in the research by mapping and mentioned above. On sub-figures 2a and 2c we can see the laser introduction into the brain and its direct stimulation of the structures. While influencing PVN during 1 hour the food intake has significantly increased, that is shown on sub-figure 2b. AGRP neurons inhibit PVH under laser stimulation. The inhibition is powerful enough to cause the acute hunger. Meanwhile, photostimulation of PBN does not influence the level of food intake significantly; it remains at about the same level, which is reflected on sub-figure 2d. This means that AGRP neurons influence food intake through PVH, meanwhile PBN does not respond to AGRP neurons stimuli powerful enough to cause the acute hunger.

Figure 5 helps to understand the principles of deconstruction of some neural circuits leading to increasing of food intake. The figure demonstrates the involvement of different pathways depending on the increasing the food intake, and by estimating the data provided on the figure we may think of possible methods of decreasing the food intake. It is obvious from sub-figures 5a and 5b, that OXT influence decreases the acute hunger in mice studied. It is shown on sub-figure 5b, that OXT influence not just decreases the inhibiting influence of AGPR onto PVH resulting in acute hunger, but also does not provide such a fast increasing of food intake right after photostimulation is applied onto the structures. We can also see on sub-figures 5d and 5e that the food consumption is increased in bilateral OXT pathways the most significantly and it decreases almost to the primary level after the stimulation is. Unlike bilateral OXT, AGRP + OXT – contralateral shows the biggest response to photostimulation, although the consumption of the food after the stimulus is released decreases compared to primary level of food intake in mice with the same scheme of conduction. Figure 5 also demonstrates us the scheme of deconstructing the circuit by breaking the inhibition of OXT. As it has been mentioned above, OXT influence decreases the amount of food taken. AGRP neurons may target OXT neurons causing their inhibition. It is shown on sub-figure 5c that targeting of the PVH not involving OXT breaks the circuit and decreases the acute hunger. Different combinations of targeting different neurons populations might be possible depending on genes present in an individual, as some of the gene mutations may predispose an individual to functioning of any type of these circuits.

This study would be very useful in developing different schemes of treatment for patients with obesity and metabolic disorders that are accompanied with increasing body weight. Authors mention, that OXT neurons are lacking in Prader-Willi syndrome and SIM1 gene mutations that lead to feeding behavior disorders and obesity (Atasoy et al., 2012). That proves the importance of the study towards feeding behavior disorders. Another important achievement of the researchers is that they have performed structural mapping of AGRP and it is now available to estimate all the connections of this group of neurons, as it might influence different parts of the brain, thus different functions. It is justified in the paper that the connection between forebrain and hindbrain. It also helps to understand not only the structural basis of the circuits responsible for the feeding behavior, but also the chemical one. This research has revealed several new circuits that were unknown and not studied before, thus it opens a big field for studying. The research has also indicated GABA, one of the most used neuromediators in the organism, to be responsible for stimulating or silencing the acute hunger. It is also very interesting to know that AGRP neurons target OXT population of PVH neurons and that oxytocin inhibits PVH’s influence on feeding behavior, which might be useful for understanding some physiological conditions oxytocin is involved in (pregnancy, love etc.). I believe, this topic will be developed and the knowledge acquired through this research will help a lot of people to make their lives better.

References

Atasoy, J. N. Betley, H. H. Su, S. M. Sternson (2009). Deconstruction of a neural circuit for hunger. Nature.; 488 (7410): 172–177.