Habenula

In neuroanatomy, habenula (diminutive of Latin habena meaning rein) originally denoted the stalk of the pineal gland (pineal habenula; pedunculus of pineal body), but gradually came to refer to a neighboring group of nerve cells with which the pineal gland was believed to be associated, the habenular nucleus. The habenular nucleus is a set of well conserved structures in all vertebrate animals.

Currently, the Terminologia Anatomica term refers exclusively to this separate cell mass in the caudal and dorsal aspect of the dorsal thalamus (the epithalamus), embedded in the posterior end of the medullary stria from which it receives most of its afferent fibers. By way of the retroflex fasciculus (habenulointerpeduncular tract) it projects to the interpeduncular nucleus and other paramedian cell groups of the midbrain tegmentum.

The habenula receives input from the brain via the stria medullaris thalami and outputs to many midbrain areas involved in releasing neuromodulators, such as dopamine, norepinephrine, and serotonin.

Anatomy
The habenula was traditionally divided into lateral (limbic) and medial (motor) parts. Detailed examination of the region in the rat, however, suggested that the lateral part should be further divided into ten distinct subnuclei and the medial into five distinct subnuclei.

Lateral habenula
The primary input regions to the lateral habenula are the lateral preoptic area (bringing input from the hippocampus and lateral septum), the ventral pallidum (bringing input from the nucleus accumbens and mediodorsal nucleus of the thalamus), the lateral hypothalamus, and the internal segment of the globus pallidus (bringing input from other basal ganglia structures).

Neurons in the lateral habenula are ‘reward-negative’ as they are activated by stimulus associated with unpleasant events, the absence of the reward or punishment especially when this is unpredictable. Reward information to the lateral habenula comes from the internal part of the globus pallidus.

The outputs of the lateral habenula target dopaminergic regions (substantia nigra pars compacta and the ventral tegmental area), serotinergic regions (median raphe and dorsal raphe nuclei), and a cholinergic region (the laterodorsal tegmental nucleus). This output inhibits dopamine neurons in substantia nigra pars compacta and the ventral tegmental area, with activation in the lateral habenula linking to deactivation in them, and vice versa, deactivation in the lateral habenula with their activation. The lateral habenula functions to oppose the action of the laterodorsal tegmental nucleus in the acquisition of avoidance responses but not the processing of avoidance later on when it is a memory, motivation or its execution.

Medial habenula
Input to the medial habenula comes from a variety of regions and carries a number of different chemicals. Input regions include septal nuclei (the fimbrialis septi and triangularis septi nuclei), dopaminergic inputs from the interfascicular nucleus of the ventral tegmental area, noradrenergic inputs from the locus ceruleus, and GABAergic inputs from the diagonal band of Broca.

The medial habenula sends outputs of substance P and acetylcholine to the interpeduncular nucleus as well as to the pineal gland.

Functions
The habenular nuclei have been shown to be involved in many functions, including pain processing, reproductive behavior, nutrition, sleep-wake cycles, stress responses, and learning. Recent demonstrations using fMRI and single unit electrophysiology have closely linked the function of the lateral habenula with reward processing, in particular with regard to encoding negative feedback or negative rewards. Matsumoto and Hikosaka suggested in 2007 that this reward and reward-negative information in the brain might "be elaborated through the interplay among the lateral habenula, the basal ganglia, and monoaminergic (dopaminergic and serotonergic) systems" and that the lateral habenula may play a pivotal role in this "integrative function". Recent evidence suggests that neurons in the lateral habenula signal signed information-prediction errors in addition to signed reward-prediction errors.

Depression
Both the medial and lateral habenula show reduced volume in those with depression. Neuron cell numbers were also reduced on the right side. Such changes are not seen in those with schizophrenia. Deep brain stimulation of the major afferent bundle (i.e., stria medullaris thalami) of the lateral hebenuala has been used for treatment of depression where it is severe, protracted and therapy-resistant.