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Habenula

The diencephalon is the caudal part of the forebrain and is almost entirely surrounded by the cerebral hemispheres. It is centrally located within the brain and forms the lateral walls of the third ventricle. It connects the midbrain to the forebrain and consists of several components, most notably the epithalamus, thalamus, subthalamus, metathalamus and hypothalamus.

This article will focus on the habenula (a.k.a. habenular nuclei), a set of nuclei found in the epithalamus, the most caudal and dorsal region of the diencephalon.

Key facts about the habenula
Structure Medial habenular nucleus, lateral habenular nucleus
Location Epithalamus (diencephalon)
Function Medial habenular nucleus: mood regulation and fear memory
Lateral habenular nucleus
: Mood and behavior expression, sleep mechanism control
Contents
  1. Definition
  2. Medial habenula
  3. Lateral habenula
  4. Functions
    1. Medial habenula
    2. Lateral habenula
  5. Clinical relations
  6. Sources
+ Show all

Definition

The habenula is a small, bilateral structure in the epithalamus of the diencephalon. It is further divided into two subregions:

  • the medial habenula (MHb)
  • the lateral habenula (LHb)

The medial habenula is a densely packed, deeply stained mass of cholinergic neurons, whereas the lateral habenula is more dispersed, paler stained and contains dopaminergic and serotonergic neurons.

Collectively, the habenular nuclei underlies the habenular trigone (a triangular depression in the wall of the third ventricle), posterior to the superior colliculus and lateral to the posterior part of the tenia thalami. The habenular commissure connects the habenulae on each side of the brain. The habenula originally denoted the stalk of the pineal gland (to which the habenula lies anterior to) however over time, it came to refer to the aforementioned nuclei which lie adjacent to it.

Medial habenula

The medial habenula (or medial habenular nuclei) receive afferents (input) from the medial and lateral septal nuclei. They project their efferents (output) almost entirely to the interpeduncular nucleus of the midbrain through the habenulointerpeduncular tract (or retroflex fasciculus). This tract is a noradrenergic and serotonergic pathway.

Additionally, some efferents from the habenula reach the pineal gland through the habenulopineal tract.

Lateral habenula

The lateral habenula (or lateral habenular nuclei) projects its efferents (output) directly to the median and dorsal raphe nuclei, substantia nigra pars compacta, and the ventral tegmental nuclei (of Tsai). It receives its input from the ventral tegmental area.

The lateral habenular nuclei can be regarded as an ‘anatomical hub’ linking various structures, including the septum, hypothalamus, basal forebrain, globus pallidus and prefrontal cortex. This is primarily achieved via the dopaminergic, serotonergic and noradrenergic pathways.

Habenula connectivity. Image depicts inputs (green) and outputs (blue) to and from the lateral habenula (LHb) and medial habenula (MHb) subnuclei.

Functions

The medial and lateral habenular nuclei receive afferent fibers from the basal ganglia and limbic system, the epicenter of emotional and behavioral expression. Despite being a relatively small structure in the brain, the human habenula acts as a cell station integrating olfactory, visceral and somatic afferent pathways. The physiological functions of the habenula are not fully understood. Yet, studies have shown that the medial and lateral habenula have different functional roles.

Medial habenula

Little is known about the specific functions of the medial habenula. Its morphology (small and elongated) and its location in the brain (proximity to ventricles) pose difficulties when recording neuronal activity in vivo. Histological and lesion studies have linked it with the following:

  • Mood regulation and fear memory by influencing the activity of cholinergic neurons. Their activation reduces the expression of fear memory.

Lateral habenula

The lateral habenula nuclei have a variety of functions but are mainly involved in the following:

  • Behavioral expression by influencing the activity of serotonin and dopamine neurons.
  • Emotional expression relative to pain, stress and anxiety. It has been suggested that a dysregulation of the lateral habenula can lead to depressive illness and negative emotions.
  • Sleep mechanism control. The lateral habenular nuclei are connected to the pineal gland, which is responsible for regulating the sleep-wake cycle via the secretion of melatonin.

Learn more about the structure and parts of the diencephalon with this study unit!

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