Memorizing and predicting aversive or unpleasant events is a critical function of neural circuits responsible for survival and emotional well-being.  There is much interest in how the brain creates the signals associated with negative emotions in order to better understand how imbalances can lead to affective disorders such as depression and anxiety.  However, it is unclear which areas of the brain control feelings of discomfort and aversion. 

Now, a study from researchers at Karolinska Institutet maps pathways in the mouse brain associated with aversion.  The team states it is hoped by understanding the structure and function of this fear and aversion circuitry, it will be possible to design intervention strategies for pathological fear conditions.  The opensource study is published in the journal Molecular Psychiatry.

Mapping emotions in the brain

Previous studies have indicated a brain structure called the habenula controls positive and negative emotions in animal models. Moreover, clinical cases have been conducted with patients suffering from depression where deep brain stimulation of the habenula has been beneficial.

The habenula controls both dopamine and the neurotransmitter serotonin, which is thought to play a significant part in the sense of wellbeing, however, it is unclear how the habenula is regulated.  The current study identifies which networks in the mouse brain control the habenula, and what role they play in aversion.

The current study uses optogenetics, a method using light to activate specific neurons in order to study how the activation of different networks affects behavior, to identify the nerve cells involved in aversion, and map their interconnections. 

Results show lateral habenula (LHb)-projecting lateral hypothalamic area (LHA) neurons are responsible for encoding negative value.  Data findings show activation of LHA glutamatergic neurons produces strong aversive responses, and shape the value of actions.

Pinpointing aversion in the brain

The group states further recordings using imaging calcium dynamics showed LHA glutamatergic neurons formed activity clusters representing distinct reward or aversion signals, including a population responding to mild foot shocks and predicted aversive events.  They also observed the LHb-projecting LHA glutamatergic neurons encode negative valence and rapidly develop a prediction signal for negative events or aversion.

The team surmises they have identified a specific pathway running between the hypothalamus and the habenula, which can be modulated using optogenetics to control the feeling of aversion.  For the future, the researchers state their data could lead to the development of new treatments that can rebalance the brain’s networks in disorders such as depression or anxiety.

Source: Karolinska Institutet

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