by Scientists have recently discovered a new neural circuit in the brain that is responsible for generating a strong sense of discomfort when activated. This breakthrough finding also suggests that the subthalamic nucleus, a brain structure that controls voluntary movements, may play a role in the development of depression. The study, published in the scientific journal Cell Reports, could potentially lead to improved treatments for Parkinson’s disease.
Previous research conducted by the team had shown that mice with an activated subthalamus tend to seek to distance themselves from the stimulation. In the current study, they were able to establish that this behavior is associated with aversion and that the avoidance response persists even after the deactivation of the subthalamic nucleus. The mice exhibited the same strong avoidance behavior when placed in the same environment at a later time. These associations were strong enough to sustain the response.
Aversion is the opposite of reward and plays a crucial role in helping us avoid unpleasant experiences. In humans, it is known that heightened activation of the brain’s aversion system can contribute to the development of depression.
The researchers not only identified the specific brain region responsible for aversion in this study but also identified neural circuits originating in the subthalamic nucleus that directly connect to the brain’s emotional system, which becomes active during periods of extreme discomfort.
The discovery that the subthalamus is involved in aversion and avoidance behavior has significant implications for two main reasons. Firstly, it enhances our understanding of the brain’s emotional system and how brain activity can give rise to psychiatric symptoms such as depression and apathy. Secondly, it offers a potential explanation as to why some Parkinson’s disease patients, who are treated with deep brain stimulation (DBS) targeting the subthalamus, may experience side effects such as severe depression.
In Parkinson’s disease, the subthalamus is excessively active, but DBS using implanted electrodes can effectively ‘normalize’ its activity, alleviating symptoms like tremors and motor issues. However, some patients may still experience adverse reactions, including depression.
With this new research, we now have a better neurobiological understanding of the link between the subthalamus and aversion, as well as its connection to the brain’s depression center. This knowledge will help us improve the precision of clinical treatments using DBS for Parkinson’s disease, essential tremor, and obsessive-compulsive disorder. The ultimate goal is to treat symptoms without causing severe side effects, explains Mackenzie, one of the researchers involved in the study.
The project involved collaboration between researchers at Uppsala University and Bordeaux University and received funding from various organizations, including the Bertil Hållsten Research Foundation, the Swedish Brain Foundation, the Parkinson’s Foundation, the Michael J Fox Foundation, the Åhlén Foundation, the Wenner-Gren Foundations, and the Swedish Research Council.
To conduct the study, the researchers utilized optogenetics, which allowed them to selectively activate or deactivate individual neurons in the subthalamic nucleus of genetically modified mice. By using light-sensitive proteins on the surfaces of these neurons, they were able to accurately target the subthalamic nucleus and study the effects of neuron activity on the mice’s behavior.
Overall, this groundbreaking research provides valuable insights into the neural mechanisms underlying aversion and depression, offering potential avenues for more effective treatments for Parkinson’s disease and related conditions.
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1. Source: Coherent Market Insights, Public sources, Desk research
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