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A second golden age for the habenula: reward and disappointment

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During the 80s, habenular researchers produced some very high quality reports that illuminated the anatomy and possible functions of this small but important brain region. For several reasons, habenula research was very slow for about two decades. Recently, a seminal work by Okihide Hikosaka’s lab at NIH ...

During the 80s, habenular researchers produced some very high quality reports that illuminated the anatomy and possible functions of this small but important brain region. For several reasons, habenula research was very slow for about two decades. Recently, a seminal work by Okihide Hikosaka’s lab at NIH showed that the lateral habenula is a critical component of the reward system in that negative prediction errors (when reward is less than expected) elicit habenular cell activation and concomitant dopaminergic cell inactivation. Since then, we have seen a resurgence of habenula-related research that has rendered some intriguing results.

The habenula is a small brain region that receives input from several frontal and basal ganglia areas and sends output to the ventral tegmental area, raphe nucleus, locus coerelus, and interpeduncular nucleus. Thus, the habenula is strategically located to control the dopaminergic, serotonergic, noradrenergic and cholinergic systems of the brain. Accordingly, research (both conducted during the first and now in the second habenular golden age) has shown involvement of the habenula in a wide variety of physiological and pathological brain processes, such as addiction, learning, depression, stress response, cognition, pain sensitivity, feeding and maternal behavior.

The most studied and possibly main habenular function is the indirect control of the dopaminergic system. When a negative event happens habenular cells activate and in turn activate gabaergic cells in the rostromedial tegmental area, which inactivate dopaminergic cells. The result is decreased dopamine availability in striatal areas which signals the brain the lack of reward. Thus, the habenular signal may become a learning signal to avoid in the future behaviors that produce such output. At the same time, by virtue of its other connections, the habenular activity may impair mood, and increase attention and arousal.

Despite the fact that habenular research has increased in volume immensely in the last few years, many questions with high public health relevance remain to be elucidated. For example, the mechanisms of habenular involvement in addiction and depression, and the relative contributions of the medial and lateral habenula to several of the associated behaviors need to be studied in detail. Importantly, analogous responces in humans and animals in areas such as reward prediction and response to depression have been observed, strengthening the notion this area may play a central role in human pathology. The possibility of using the habenula as a therapeutic target for different conditions is also actively pursued by several groups.

This topic issue deals with different aspects of current habenula research and the exciting possibilities for the near future.


Important Note: All contributions to this Research Topic must be in line with the scope of the specialty and field to which they are submitted, as defined in their mission statements. Manuscripts discovered during any stage of peer review to be outside of the scope may be transferred to a suitable section or field, or withdrawn from review.

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