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New findings reveal the surprising role of the cerebellum in rewards and social behaviors



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Press release

Thursday, January 17, 2019

The NIH-funded study attracts new lights on brain circuits linked to affective and social dysfunction.

A new rodent study has shown that the brain cerebellum – known to play a role in engine coordination – also helps control brain reward circuits. The researchers discovered a direct neural connection from the cerebellum to the ventral tegmental (VTA) area of ​​the brain, which is an area well known for being involved in rewarding and coding processing. These findings, published in Science, demonstrates for the first time that the brain of the brain plays a role in controlling reward and social preference behavior and draws new light on critical brain circuits for affective and social dysfunction seen in more psychiatric disorders. The research was funded by the National Institute of Mental Health (NIMH), part of the National Institutes of Health.

This type of research is fundamental to deepening our understanding of how brain activity circuit refers to mental illness, "said Joshua A. Gordon, M.D., Ph.D., director of NIMH. The findings as described in this paper help us find out more about how the brain works, a first key step on the path to developing new treatments.

The cerebellum plays a recognized role in coordinating and regulating motor activity. However, research has also suggested that this area of ​​the brain contributes to a number of non-motor functions. For example, cerebellar abnormalities have been linked to autism, schizophrenia and substance use disorders, and brain activation in the cerebellum was related to motivation, social and emotional behaviors, and rewarding learning, each of which may be interrupted in psychiatric disorders.

These earlier findings have led Kamran Khodakhah, Ph.D., from Albert Einstein College of Medicine in New York, and colleagues asking if there is a direct link between cerebellum and VTA – a brain structure involved in controlling reward behavior and motivation. To examine this, the researchers used a technique called optogenetic, in which animal neurons are genetically modified so that they can be controlled using light pulses. The researchers used this technique in mice, activating neurons in the cerebellum associated with VTA. The researchers found that activation of cerebellar neurons led to an increase in activation in VTA of mice, indicating a working relationship between these two brain structures.

Once the neural link between these two brain structures has been confirmed, researchers have investigated whether the cerebellum feeds to VTA behavior influenced by rewards and social preferences. The researchers placed the mice in a square-shaped open room and used light pulses to activate cerebellar neurons bound to VTA whenever the mice entered a particular part of the room, called the "reward dial". Mice have shown a strong preference for spending the quadrant of rewards, freely choosing to spend more than 70% of their time in the field. In addition, the researchers found that mice were willing to work for activation in this area of ​​the brain and spend time in conditions they would not usually prefer (light vs. darker areas) to receive this activation. Together, the findings suggest that activation of cerebellar projections at VTA is reward for mice and that the cerebellum plays a role in reward-related behaviors.

To examine whether cerebral infarctions in VTA affected social behaviors, researchers tested mice using a three-room social task where the mice could choose to spend time in a room with another center-room mouse (social room) or in a room containing a non-social object. At first, the mice preferred to be in the social room, but after the researchers inactivated the cerebellar projectiles in VTA, the mice did not show this preference. In addition, the continued silence of the cerebellar-VTA pathway was found to completely prevent expression of social preference behavior in mice, findings indicating that cerebellar inflows into VTA are required for social preference behavior in mice.

The results of this study suggest a major and previously unrecognizable role of the cerebellum in creating and controlling reward and social preference behaviors. Although there is much more to be explored, identifying this direct neural pathway can help explain the role of this circuit in disorders involving social rewarding and social processing systems such as addiction, autism and schizophrenia, and may indicate future goals for intervention and management symptoms.

The role of cerebellar circuits in behaviors relevant to mental health is a studied area where we have just begun to see increased interest, "said Janine Simmons, PhD, Ph.D., Chief of the NIMH Social and Affective Neuroscience Program. We are always excited to see this kind of innovation in Behavioral Neurosciences, and these results demonstrate how much remains to be learned.

In future studies, researchers plan to test whether the cerebellum-VTA pathway can be manipulated using drugs or optogenetics to treat addiction and prevent relapse after treatment.

Cerebellar abnormalities are also related to a number of other mental disorders, such as schizophrenia, said Dr. Khodakhah. We want to find out if this path also plays a role in these disorders.

This press release describes a basic research. Basic research increases the understanding of human behavior and biology, which is fundamental to advancing new and better methods of preventing, diagnosing and treating disease. Science is an unpredictable and incremental process – every advance of research is based on past discoveries, often in unexpected ways. Most clinical advancements would not be possible without the knowledge of fundamental fundamental research.

About the National Institute of Mental Health (NIMH): The NIMH mission is to transform the understanding and treatment of mental illness through basic and clinical research, paving the way for prevention, recovery and healing. For more information, visit the NIMH website.

About the National Institutes of Health (NIH):
NIH, the national medical research agency, includes 27 institutes and centers and is a component of the US Department of Health and Human Services. NIH is the leading federal agency that carries out and supports basic, clinical and translational medical research and investigates the causes, treatments and treatments for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

NIH … Turning Discovery in Health®

Reference

Carta, I., Chen, C.H., Schott, A., Dorizan, S., & Khodakhah, K. (in press). Cerebellar modulation of the reward circuit and social behavior. Science. Online January 17, 2019.

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