The medial habenula: still neglected

Abstract

The habenula is a small, bilateral brain structure located at the dorsal end of the diencephalon. This structure sends projections to the dopaminergic striatum and receives inputs from the limbic forebrain, making the habenula a unique modulator of cross-talk between these brain regions. Despite strong interest in the habenula during the seventies and eighties (Herkenham and Nauta, 1977; Beckstead, 1979; Beckstead et al., 1979; Herkenham and Nauta, 1979; Caldecott-Hazard et al., 1988), interest waned due to lack of a clearly identifiable functional role. Following Matsumoto and Hikosaka's seminal work on the lateral habenula as a predictor of negative reward in monkeys, the habenula has undergone a resurgence of scientific interest. Matsumoto and Hikosaka demonstrated an increase in habenular neuron firing when monkeys did not receive an expected juice reward (Matsumoto and Hikosaka, 2007). Studies have shown that increased habenular activity inactivates dopaminergic cells in the Rostromedial Tegmental Nucleus (RMTg) through GABAergic mechanisms (Jhou et al., 2009a,b). Additional studies link habenular activity to the regulation of serotonin and norepinephrine, suggesting the habenula modulates multiple brain systems (Strecker and Rosengren, 1989; Amat et al., 2001). These discoveries ushered in a series of new studies that have refocused attention on the lateral habenula and the importance of this small brain structure (Bianco and Wilson, 2009; Jhou et al., 2009a; Matsumoto and Hikosaka, 2009; Sartorius et al., 2010; Savitz et al., 2011). Recently, Geisler and Trimble reviewed this renewed interest in: The Lateral Habenula: No Longer Neglected (Geisler and Trimble, 2008). While the lateral habenula (LHb) has been extensively studied, the anatomically and histochemically distinct medial habenula (MHb) remains largely understudied. This short review argues that the MHb is functionally important and should be studied more aggressively.

GPR139, an Orphan Receptor Highly Enriched in the Habenula and Septum, Is Activated by the Essential Amino Acids l-Tryptophan and l-Phenylalanine

“…In contrast to the lateral habenula, the medial habenula is relatively understudied. It is a conserved region of the brain that has been considered as a part of the limbic circuits involved in the regulation of mood and stress (Morris et al, 1999;Hsu et al, 2014;Proulx et al, 2014;Viswanath et al, 2013).…”

Expression of mu opioid receptor in dorsal diencephalic conduction system: New insights for the medial habenula

“…The LHb, which has pallidal and hypothalamic afferences and mainly projects to midbrain and hindbrain structures such as the raphe nuclei and VTA (Lecourtier and Kelly, 2007, Jhou et al, 2009, Kaufling et al, 2009, Kim, 2009), was shown involved in aversion and behavioral avoidance (Lammel et al, 2012, Stamatakis and Stuber, 2012, Ilango et al, 2013). The MHb receives septal inputs and projects primarily to the IPN, and has been less studied (Viswanath et al, 2013). This nucleus was proposed to regulate inhibitory controls, cognition-dependent executive functions, place aversion learning (Darcq et al, 2011, Kobayashi et al, 2013) and the nicotine withdrawal syndrome (Dani and De Biasi, 2013, Kobayashi et al, 2013, Dao et al, 2014).…”

10.5937/mckg48-5899 = Functional and anatomical aspects of the habenular complex of epithalamus

“…takođe, uočeno je povećanje metabolizma u MHb i interpedunkularnom jedru, kao njegovom glavnom ciljnom području, kao i smanjenje metaboličke aktivnosti u ventralnom tegmentalnom području, bazalnim ganglijama i amigdalama (49). Promene u MHb mogu biti posledica smanjene ekspresije interleukina-18, proinflamatornog citokina u gornjem subnukleusu ovog jedra (17,50). Pokazano je da su kod pacijenata obolelih od depresije u poređenju s kontrolnom grupom, zapremina i broj ćelija habenule smanjeni, kao i ćelijska površina medijalnog habenularnog jedra (51).…”

“…Poremećaj ovog balansa kod pušača vodi ka većoj konzumaciji nikotina, koja može da izazove selektivno oštećenje fasciculus retroflexusa, kao glavnog eferentnog puta habenule. Ovi rezultati ukazuju na to da su naChr receptori medijalnog habenularnog jedra uključeni u nastanak raznih oblika nikotinske zavisnosti (17) ekscesivni unos amfetamina i kokaina dovodi do poremećene dopaminske centralne regulacije i može dovesti do paranoje, deluzija, halucinacija i razvoja slike tzv. paranoidne shiofrenije.…”

“…takođe, opisane su projekcije medijalnog habenularnog jedra, koje odlaze u lateralno hebenularno jedro, preko kojih MHb može da kontroliše rad lHb. Ove projekcije nisu recipročne (16,17).…”