Habenula

Anatomy

• A small paired nucleus in the epithalamus, dorsomedial to the thalamus, at the posterior-superior edge of the third ventricle, in front of the pineal gland.
• Medial and lateral habenula; the lateral habenula (LHb) is a key part of the reward and punishment circuit.
• Input via the stria medullaris from the basal forebrain, lateral hypothalamus and pallidal border region; output via the fasciculus retroflexus to the interpeduncular nucleus, RMTg, VTA and raphe.

Functions

• Negative reward prediction error: activates when an expected reward does not come or punishment arrives (Matsumoto and Hikosaka, 2007).
• Inhibits VTA dopamine neurons via the RMTg, as well as raphe serotonin neurons; supports avoidance and giving up.
• Contribution to sleep and circadian rhythm regulation.

Connections and chemistry

• Basal forebrain, lateral hypothalamus and pallidal border region → habenula (stria medullaris)
• Lateral habenula → RMTg → VTA and substantia nigra (inhibition of dopamine)
• Lateral habenula → raphe nuclei (serotonin)
• Medial habenula → interpeduncular nucleus (nicotine, anxiety)

Development

Developmental course through childhood and adolescence.

• An evolutionarily conserved, early-developing structure; developmental data in humans are limited.
• Animal models report that early-life stress increases lateral habenula activity.

Clinical

• Depression: lateral habenula hyperactivity has been shown in animal models; ketamine’s rapid antidepressant effect has been partly attributed to blocking burst firing in the LHb (Yang et al., 2018).
• Habenular deep brain stimulation has been tried at the case level in adult treatment-resistant depression.
• Substance use and the negative affect of withdrawal: part of the avoidance circuit.

Treatment

This region from the perspective of medication, psychotherapy and neuromodulation. Letter badges are evidence levels.

• Esketamine (nasal spray, NMDA antagonist): FDA-approved for adult treatment-resistant depression (2019); in animal studies its rapid effect has been attributed to blocking burst firing in the lateral habenula (Yang et al., 2018). No routine use in adolescents. B
• Habenular deep brain stimulation: case-level only in treatment-resistant depression, experimental. C

Assessment

Neuropsychological tasks and measures that probe this region's function.

• Probabilistic reward and punishment learning tasks (negative prediction error)
• High-resolution MRI and fMRI (research; its small size makes measurement difficult)

Lesions and damage

Clinical findings expected with damage or dysfunction.

• In animals, lateral habenula lesions reduce learned-helplessness-like behavior.

In the model

How this structure is defined in the 3D model, and the data source.

CIT168 habenula probability map (right/left); the structure is very small (about 60 voxels per side), so its shape is approximate.

References

Full citations for the card; links go to the paper (DOI) or a PubMed search.

1. Matsumoto M, Hikosaka O. Lateral habenula as a source of negative reward signals in dopamine neurons. Nature 2007;447:1111–1115. DOI: 10.1038/nature05860
2. Yang Y et al. Ketamine blocks bursting in the lateral habenula to rapidly relieve depression. Nature 2018;554:317–322. DOI: 10.1038/nature25509