| 1 | J. Neurosci. 2008 Nov 28: 11825-9 |
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| PMID | 19005047 |
| Title | Habenula: crossroad between the basal ganglia and the limbic system. |
| Abstract | There is a growing awareness that emotion, motivation, and reward values are important determinants of our behavior. The habenula is uniquely positioned both anatomically and functionally to participate in the circuit mediating some forms of emotive decision making. In the last few years there has been a surge of interest in this structure, especially the lateral habenula (LHB). The new studies suggest that the LHB plays a pivotal role in controlling motor and cognitive behaviors by influencing the activity of dopamine and serotonin neurons. Further, dysfunctions of the LHB have also been implicated in psychiatric disorders, such as depression, schizophrenia, and drug-induced psychosis. |
| SCZ Keywords | schizophrenia |
| 2 | Front Hum Neurosci 2014 -1 8: 174 |
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| PMID | 24734015 |
| Title | The role of the habenula in drug addiction. |
| Abstract | Interest in the habenula has greatly increased in recent years. The habenula is a small brain structure located posterior to the thalamus and adjacent to the third ventricle. Despite its small size, the habenula can be divided into medial habenula (MHb) and lateral habenula (LHB) nuclei that are anatomically and transcriptionally distinct. The habenula receives inputs from the limbic system and basal ganglia primarily via the stria medullaris. The fasciculus retroflexus is the primary habenular output from the habenula to the midbrain and governs release of glutamate onto gabaergic cells in the rostromedial tegmental nucleus (RMTg) and onto the interpeduncular nucleus. The resulting GABA released from RMTg neurons inactivates dopaminergic cells in the ventral tegmental area/substantia nigra compacta. Through this process, the habenula controls dopamine levels in the striatum. Thus, the habenula plays a critical role in reward and reward-associated learning. The LHB also modulates serotonin levels and norepinephrine release, while the MHb modulates acetylcholine. The habenula is a critical crossroad that influences the brain's response to pain, stress, anxiety, sleep, and reward. Dysfunction of the habenula has been linked to depression, schizophrenia, and the effects of drugs of abuse. This review focuses on the possible relationships between the habenula and drug abuse. |
| SCZ Keywords | schizophrenia |
| 3 | Front Behav Neurosci 2015 -1 9: 295 |
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| PMID | 26582981 |
| Title | Ongoing behavioral state information signaled in the lateral habenula guides choice flexibility in freely moving rats. |
| Abstract | The lateral habenula (LHB) plays a role in a wide variety of behaviors ranging from maternal care, to sleep, to various forms of cognition. One prominent theory with ample supporting evidence is that the LHB serves to relay basal ganglia and limbic signals about negative outcomes to midbrain monoaminergic systems. This makes it likely that the LHB is critically involved in behavioral flexibility as all of these systems have been shown to contribute when flexible behavior is required. Behavioral flexibility is commonly examined across species and is impaired in various neuropsychiatric conditions including autism, depression, addiction, and schizophrenia; conditions in which the LHB is thought to play a role. Therefore, a thorough examination of the role of the LHB in behavioral flexibility serves multiple functions including understanding possible connections with neuropsychiatric illnesses and additional insight into its role in cognition in general. Here, we assess the LHB's role in behavioral flexibility through comparisons of the roles its afferent and efferent pathways are known to play. Additionally, we provide new evidence supporting the LHB contributions to behavioral flexibility through organization of specific goal directed actions under cognitively demanding conditions. Specifically, in the first experiment, a majority of neurons recorded from the LHB were found to correlate with velocity on a spatial navigation task and did not change significantly when reward outcomes were manipulated. Additionally, measurements of local field potential (LFP) in the theta band revealed significant changes in power relative to velocity and reward location. In a second set of experiments, inactivation of the LHB with the gamma-aminobutyric acid (GABA) agonists baclofen and muscimol led to an impairment in a spatial/response based repeated probabilistic reversal learning task. Control experiments revealed that this impairment was likely due to the demands of repeated switching behaviors as rats were unimpaired on initial discrimination acquisition or retention of probabilistic learning. Taken together, these novel findings compliment other work discussed supporting a role for the LHB in action selection when cognitive or emotional demands are increased. Finally, we discuss future mechanisms by which a superior understanding of the LHB can be obtained through additional examination of behavioral flexibility tasks. |
| SCZ Keywords | schizophrenia |