TY - JOUR T1 - The Role of the Lateral Habenula in Inhibitory Learning from Reward Omission Experiences JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0016-21.2021 SP - ENEURO.0016-21.2021 AU - Rodrigo Sosa AU - Jesús Mata-Luévanos AU - Mario Buenrostro-Jáuregui Y1 - 2021/05/07 UR - http://www.eneuro.org/content/early/2021/05/07/ENEURO.0016-21.2021.abstract N2 - The lateral habenula (LHb) is a phylogenetically primitive brain structure that plays a key role in learning to inhibit distinct responses to specific stimuli. This structure is activated by primary aversive stimuli, cues predicting an imminent aversive event, unexpected reward omissions, and cues associated with the omission of an expected reward. The most widely described effect of LHb activation is acutely suppressing midbrain dopaminergic signaling. However, recent studies have identified multiple means by which the LHb foster this effect as well as other mechanisms of action. These findings reveal the complex nature of LHb function. The present paper reviews the role of this structure in learning from reward omission experiences. We approach this topic from the perspective of computational models of behavioral change that account for inhibitory learning to frame key findings. Such findings are drawn from recent behavioral neuroscience studies that use novel brain imaging, stimulation, ablation, and reversible inactivation techniques. Further research and conceptual work are needed to clarify the nature of the processes related to updating motivated behavior in which the LHb is involved. As yet, there is little understanding of whether such mechanisms are parallel or complementary to the well-known modulatory function of the more recently evolved prefrontal cortex.Significance StatementThe lateral habenula is a brain structure that has received a great deal of attention and has been a hot topic in the past decades. Consequently, this research field has been extensively reviewed. We review in detail some key recent findings that are pivotal in framing the role of the lateral habenula in well-described associative learning phenomenon, conditioned inhibition. This specific topic has not been considered deeply enough in previous review articles. We also outline the possible mechanisms by which the lateral habenula updates behavior by means of two identified pathway categories (inhibitory and excitatory). This provides a comprehensive account potentially embracing more issues than previously thought, refines our understanding of multiple reward-related mechanisms, and raises novel research questions. ER -