The habenula: from stress evasion to value-based decision-making

Top Cited Papers
Publisher Website
Google Scholar
Abstract
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). 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. 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. 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. 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. 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. 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.