Key Points
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The habenula is a phylogenetically old brain structure that is present in virtually all vertebrate species. It receives inputs from the limbic system and the basal ganglia and sends outputs to midbrain areas that are involved in the release of dopamine (the substantia nigra pars compacta and ventral tegmental area) and serotonin (the median and dorsal raphe nuclei).
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Having co-evolved with the pineal gland, which regulates circadian and seasonal rhythmicity, the habenula has a role in the control of sleep and sleep-like behaviour. It may help to minimize energy expenditure by suppressing body movements during sleep-like states.
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Neurons in the lateral habenula encode negative reward prediction errors and provide dopamine neurons with reward-related signals by (indirectly) inhibiting them. Thus, the lateral habenula may have a role in reinforcement learning.
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Lateral habenula neurons are excited by sensory stimuli that predict aversive outcomes as well as by the aversive outcomes themselves. By sending such negative value signals through dopamine neurons, the lateral habenula may contribute to the suppression of body movements that lead to aversive outcomes.
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Stress resulting from prolonged exposure to aversive stimuli may cause hyperactivity of lateral habenula neurons and immune responses in the medial habenula. These responses may lead to a general suppression of motor activity and other behavioural changes through modulation of the activity of dopamine and serotonin neurons.
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Dysfunctions of the habenula may contribute to various psychiatric disorders, including major depression and schizophrenia. In patients with depression and in animal models of depression, neural activity is abnormally increased in the habenula and in areas that receive inputs from the habenula.
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It is speculated that the habenula evolved as a general motor controller devoted to circadian control of behaviour and that it has subsequently acquired the ability to control value-based decision-making as more brain areas formed connections to, and received projections from, the habenula.
Abstract
Surviving in a world with hidden rewards and dangers requires choosing the appropriate behaviours. Recent discoveries indicate that the habenula plays a prominent part in such behavioural choice through its effects on neuromodulator systems, in particular the dopamine and serotonin systems. By inhibiting dopamine-releasing neurons, habenula activation leads to the suppression of motor behaviour when an animal fails to obtain a reward or anticipates an aversive outcome. Moreover, the habenula is involved in behavioural responses to pain, stress, anxiety, sleep and reward, and its dysfunction is associated with depression, schizophrenia and drug-induced psychosis. As a highly conserved structure in the brain, the habenula provides a fundamental mechanism for both survival and decision-making.
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Acknowledgements
I would like to thank my colleagues Masayuki Matsumoto, Simon Hong and Ethan Bromberg-Martin, who have discovered various properties of the primate habenula and have provided me with excellent ideas on the function of the habenula. I also thank Ilya Monosov for helping me improve the manuscript. This research was supported by the Intramural Research Program at the National Institutes of Health, National Eye Institute.
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Glossary
- Sleep-associated atonia
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Depression of skeletal muscle tone that occurs during rapid eye movement sleep. The brain remains active with fast eye movements, but both sensory input and motor output are suppressed.
- Suprachiasmatic nucleus
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The master circadian pacemaker in the mammalian brain. Its circadian rhythm is generated by a gene expression cycle in individual neurons in this nucleus, but it also receives light intensity signals directly from the retina.
- Reinforcement learning
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A sub-area of machine learning concerned with how an agent learns from the consequences of its actions, rather than from being explicitly taught. It is essentially trial-and-error learning. The agent seeks to learn to select actions that maximize the accumulated reward over time.
- Avoidance learning
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A type of learning in which a certain behaviour results in the cessation of an aversive stimulus — for example, a rat is placed in a box where a warning signal, such as a tone, is followed by an electric shock. As the sequence is repeated, the rat learns to jump over to the adjacent box before the shock is delivered.
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Hikosaka, O. The habenula: from stress evasion to value-based decision-making. Nat Rev Neurosci 11, 503–513 (2010). https://doi.org/10.1038/nrn2866
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DOI: https://doi.org/10.1038/nrn2866
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