During embryonic development, there is a region of the neural tube called the diencephalon which gives rise to the posterior forebrain structures. The diencephalon consists of the thalamus proper (or dorsal thalamus), the hypothalamus, the epithalamus, and the ventral thalamus (or subthalamus). The third ventricle may be regarded as the cavity of the diencephalon.
The epithalamus, a subdivision of the diencephalon, lies in relation to the posterior part of the roof of the third ventricle, and in the adjoining part of its lateral wall. The structures that make up the epithalamus are:
- pineal body (or pineal gland)
- paraventricular nuclei (anterior and posterior)
- habenular nuclei (medial and lateral)
- stria medullaris thalami
- posterior commissure (epithalamic commissure)
The habenular is a nucleus of the diencephalon comprising of two parts:
- medial habenular (MHb)
- lateral habenular (LHb)
The medial and lateral habenulae or medial and lateral habenular nuclei are situated in relation to a triangular depression in the wall of the third ventricle called the habenular trigone. It lies in relation to the dorsomedial part of the thalamus. Other relations of the trigone includes the pulvinar which this trigone is medial to, but separated from by a sulcus – the sulcus habenulae. Also lying just behind the habenular trigone is the superior colliculus.
During the process of neurulation (neural tube development) and formation of the primary brain vesicles in embryonic development, the diencephalon is established from the prosencephalon. This normally occurs before the closure of the neural tube.
The lateral wall of the diencephalon becomes subdivided by the appearance of the epithalamic and hypothalamic sulci into a central part between said sulci, which proceeds to enlarge to form the thalamus. The part above the epithalamic sulcus remains small, but develops to form the epithalamus which at this stage of embryonic development is represented by the habenular nuclei and the pineal body. Finally, the third part, which lies below the hypothalamic sulcus, forms the hypothalamus.
Thus, some authors define the epithalamus as part of the diencephalon, comprising part of the habenula and the pineal gland. This definition/description of the epithalamus refers to the embryonic epithalamus.
The habenular nuclei of the left and right sides of the brain are connected by fibres (pathways) that form the habenular commissure.
Afferents of the Habenular Nuclei
The habenulae receive afferent fibres from several areas of the limbic system. Some of these afferents travel through the stria medullaris thalami (a subdivision of the epithalamus) to reach the habenular nuclei. The habenulae also receive afferents from the midbrain. The afferents from the midbrain originate from the tegmentum of midbrain and constitute a tract called the habenulopeduncular tract. This tract is a noradrenergic and serotonergic fiber bundle.
Efferents of the Habenular nuclei
Each of the medial and lateral habenular nuclei sends its axon (nerve fibre) to different targets. The medial habenular nucleus projects its efferents to the interpeduncular nucleus (IPN) through the habenulopeduncular tract (or fasciculus retroflexus), whereas the lateral habenular nucleus sends its efferents directly to the median and dorsal raphe, substantia nigra (SN), and the ventral tegmental area (VTA). Also, efferents from the habenular nuclei reach the pineal body through the habenulopineal tract.
The medial and lateral habenular nuclei have been regarded as cell stations in olfactory and visceral pathways but their functions are not understood. However, recent studies have implicated them in the following functions:
- Playing a pivotal role in motor and cognitive behaviors by regulating serotonergic and dopaminergic activities (regulating or influencing the activity of serotonin and dopamine neurons).
- Playing a role in sleep. The habenula has connections with the pineal gland, which in turn, secrete melatonin (a hormone important for regulating the circadian rhythms and promoting sleep). Some studies suggest that the habenula itself also produces melatonin, thus promoting sleep and sleep quality. Other studies have suggested that the role of the habenula in sleep may also be related to its role in depression, as depressed individuals often suffer from sleep disorders.
- Implicated in the control of emotional and social behaviors relative to pain, stress and anxiety. The lateral habenula may be involved in behaviors associated with negative emotions.
Implication of Habenula in Psychosis
Dysfunctions of the habenula have been implicated in psychosis including depression, schizophrenia, and drug-induced psychosis.
Transient depressive relapses in volunteer patients by rapidly depleting plasma tryptophan, the precursor of serotonin (5-HT), are associated with correlated increases in activity in the habenula and the dorsal raphe as the rating of depressed mood increases. In patients with chronic schizophrenia, calcification of the habenula occurs much more frequently than in age-matched normal patients. Influenza virus, which increases the risk of schizophrenia if experienced prenatally, selectively damages the habenula when introduced into the brain via the olfactory bulb. A variety of addictive drugs induce degeneration of axons in the fasciculus retroflexus which originate in the habenula. Drugs that predominantly potentiate dopamine, including D-amphetamine, methamphetamine, MDMA, cocaine, and cathinone, all induce degeneration in axons from the lateral habenula, while continuous nicotine selectively induces degeneration in axons from the medial habenula. Continuous cocaine exposure has selective neurotoxic effects on the habenula of the developing fetus similar to cocaine's effects in the adult.
It should be noted that these psychiatric disorders are associated with impairments in emotional, social, cognitive, and motor behaviors, all of which seem to be normally supported by the habenula.