Citizen Science: Finding from “Stress-induced plasticity of a CRH/GABA projection disrupts reward be

Author: Apple UYoung Jun

Sub-Heading: This article is a more accessible summary of several key findings of the esoteric piece “Stress-induced plasticity of a CRH/GABA projection disrupts reward behaviors in mice,” which was published in the journal Nature Communications on February 25, 2023, to be read by the general public.

Aim: The study aims to discover how early-life adversity has an impact on reward behaviors by conducting experiments with mice. The researchers of this study indicate hope that this study will allow scientists to gain a deeper understanding about the impact that stress can have on certain behaviors and use the newfound knowledge to help patients of mental illnesses.

Link to actual study: https://www.nature.com/articles/s41467-023-36780-x#MOESM3

How early-life adversity, or ELA, continuously impacts the activity of the reward circuit is not clear. The BLA, also known as the basolateral amygdala, that contributes to the formation of fear and is also directly related to stress and motivation is crucial in this experiment along with the NAc, or nucleus accumbens that connects motivation and action. This is because in the study, a stress-sensitive projection that connects the BLA and NAc is described. It also additionally conveys the inhibitory neurotransmitter GABA and stress reactive hormone CRH. Researchers believe that this projection plays a crucial role in carrying out disrupted incentivized behaviors provoked by ELA. A stimulation of the projection in a controlled set of male mice is found to inhibit several reward behaviors, showcasing the disruption caused by ELA and demonstrating the projection’s impacts on normal reward behaviors. In adult mice, hindering the projection restores typical reward behaviors but has little effect on controls. This indicates that the reward circuit is certainly disrupted by ELA and that the blockage of the projection described may provide a starting point to resolve mental illnesses involving abnormal reward behaviors.

Reward behavior is a motivated action taken to gain an incentive. Reward behavior is crucial to the well-being of an individual:deficiency or aberration of this reward behavior directly links to conditions such as depression. In light of recent discoveries, scientists may have found the key to helping individuals with associated mental conditions.

Reward behavior, like many other brain functions, can be disrupted by exposure to stress during childhood, coined early life adversity, or ELA. Specifically, scientists hypothesized that the Corticotropin-releasing hormone, or CRH, may influence the disruption significantly. CRH is a hormone that prompts the body to respond to stress, possibly resolving the alterations of the reward behavior that occurs.

To test the postulation, scientists first exposed the mice to developed an injection with CRH and targeted it in mice when they showed reward behaviors. The two reward tasks utilized for this experiment were food consumption and sex cue. Researchers found that whereas the projection was injected into both female and male mice, only male mice were affected as their reward behaviors were suppressed.

Taking the experiment further, the scientists induced ELA in the mice by exposing them to a stressful environment during a sensitive time. This step of the experiment was conducted solely on male mice. Researchers found that the reward behaviors were indeed disturbed by ELA. For example, the appetite of the male mice decreased. To discover whether the suppression can be reversed by using factors such as CRH, the researchers then inhibited the projection that resulted in suppression while the ELA-affected male mice were performing reward tasks. This was found to have rescued the reward behavior within the male mice, and the appetite of the mice did not decrease any further after the prohibition.

In conclusion, this study finds that ELA can severely harm individuals’ abilities to carry out certain tasks. Although scientists of this study agree that more research must be conducted to be certain about ELA’s specific functions on reward behavior, the findings indicate a positive outlook on understanding the mechanisms of stress-induced disturbance of reward behavior and the role it plays in mental illness patients.

References:

Birnie, M.T., Short, A.K., de Carvalho, G.B. et al. (2023). Stress-induced plasticity of a CRH/GABA projection disrupts reward behaviors in mice. Nat Commun, 14(1088), 1-10. https://doi.org/10.1038/s41467-023-36780-x.

Fernández-Espejo E. (2000). Cómo funciona el nucleus accumbens? [How does the nucleus accumbens function?]. Revista de neurologia, 30(9), 845–849.

Gale, G. D., Anagnostaras, S. G., Godsil, B. P., Mitchell, S., Nozawa, T., Sage, J. R., Wiltgen, B., & Fanselow, M. S. (2004). Role of the basolateral amygdala in the storage of fear memories across the adult lifetime of rats. The Journal of neuroscience : the official journal of the Society for Neuroscience, 24(15), 3810–3815. https://doi.org/10.1523/JNEUROSCI.4100-03.2004.

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The Reward Circuit: How the Brain Responds to Natural Rewards and Drugs. (2014). National Institute on Drug Abuse. https://nida.nih.gov/videos/reward-circuit-how-brain-responds-to-natural-rewards-drugs#:~:text=Deep%20within%20the%20brain%20is,motivates%20us%20to%20repeat%20behaviors.