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.

Keywords: addiction; medial habenula (MHb); nicotinic receptors; stria medullaris; tobacco.

Figure 1

The Medial habenula. (A) Mouse coronal brain section at the level of the medial habenula, stained with Nissl. Medial (MHb) and lateral (LHb) are indicated. (B,C) Pattern of general genetic co-expression in the mouse brain using the MHb (B) or the LHb (C) as seeds. Note that the expression patterns are completely different. All figures from the Allen Brain Atlas (Lein et al., 2007).