Located centrally along the dorsal diencephalic system, the habenula is divided into two structures: the medial and the lateral portions. It serves as an important relay between the forebrain and several hindbrain sites. In the last few years, a huge attention has been devoted to this structure, especially the lateral habenula (LHb), which seems to play an important role in emotion, motivation, and reward. Recent studies using techniques such as electrophysiology and neuroimaging have shown that the LHb is involved in motivational control of behavior. Its dysfunction is often associated with depression, schizophrenia, and mood disorder. This review focuses on providing a neuroanatomical and behavioral overview of some of the research previously done on the LHb. First, we describe the anatomical structure of the habenula and we explain how it is involved in reward and motivation. Then, we will discuss how this structure is linked to the limbic system, to finally provide a comparison between several studies that have used electrolytic lesions. 1. Introduction The study of the habenula started in the early 1980s [1], and it was known that this structure has the potential to control several regions of the midbrain. However, it was just recently that scientists discovered the influence of the habenula in motivational states, mood disorders, and several other mental problems [2, 3]. The habenula, which is part of the epithalamus, is composed of the lateral habenula (LHb) and the medial habenula (MHb), each having distinct functions and a unique anatomical structure. Here, we will focus on the LHb, which is more involved with pain processing, reward, motivation, and learning [4, 5]. In rodents, studies have shown that lesions at the level of the habenula cause cognitive impairment, attention deficits, hyperreactivity to stress, and schizophrenic-like symptoms [6]. Moreover, additional studies have linked the activity of the LHb to the regulation of serotonin (5-HT) and norepinephrine, suggesting that this structure modulates multiple regions in the brain [7–9]. It was also shown that neurons in the habenula are responsive to peripheral nociceptive stimulation, and when exposed to stress, the level of c-fos in this structure significantly increases [10, 11]. The habenula receives its main afferents from the septum and stria medullaris (sm) [8]. Furthermore, the habenula projects towards many areas in the midbrain that are involved in the release of neuromodulators and also towards dopaminergic midbrain nuclei such as the ventral tegmental area (VTA) [2, 12].
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