Reward and aversion encoding in the lateral habenula for innate and learned behaviours

Abstract

Throughout life, individuals experience a vast array of positive and aversive events that trigger adaptive behavioural responses. These events are often unpredicted and engage actions that are likely anchored on innate behavioural programs expressed by each individual member of virtually all animal species. In a second step, environmental cues, that are initially neutral, acquire value through the association with external sensory stimuli, and become instrumental to predict upcoming positive or negative events. This process ultimately prompts learned goal-directed actions allowing the pursuit of rewarding experience or the avoidance of a danger. Both innate and learned behavioural programs are evolutionarily conserved and fundamental for survival. Among the brain structures participating in the encoding of positive/negative stimuli and contributing to innate and learned behaviours is the epithalamic lateral habenula (LHb). The LHb provides top-down control of monoaminergic systems, responds to unexpected appetitive/aversive stimuli as well as external cues that predict the upcoming rewards or punishments. Accordingly, the LHb controls a number of behaviours that are innate (originating from unpredicted stimuli), and learned (stemming from predictive cues). In this review, we will discuss the progresses that rodent's experimental work made in identifying how LHb activity governs these vital processes, and we will provide a view on how these findings integrate within a complex circuit connectivity.

Fig. 1. The LHb guides innate and learned behaviours by encoding rewarding and aversive stimuli through complex circuit connectivity and diversity in neuronal responses.

a Schematic representing the principal LHb inputs (blue) and outputs (purple) contributing to innate and learned behaviours. Ventral tegmental area (VTA), lateral hypothalamus (LH), lateral preoptic area (LPO), ventral pallidum (VP), entopeduncular nucleus (EPN), medial septal nucleus (MS) and Prefrontal Cortex are projections to the LHb. LHb neurons send axons to VTA, Rostromedial Tegmental Nucleus (RMTg), Raphe and Laterodorsal Tegmental nucleus (LDTg). b Schematic representation of various innate behaviours that are controlled by LHb. Response to a threat (I.) and subsequent escape behaviour (Ia.) or immobility (Ib); social interactions (II.), aggressive interactions (III.) and parental behaviours (IV.). c Illustration of the average neuronal activity of LHb cells in response to a conditioned stimulus and unconditioned aversive and rewarding stimulus before and after associative learning. d Tentative model representing the neuronal and functional diversity present during the encoding of conditioned stimuli and unconditioned stimuli. Such a neuronal diversity is represented by the type I (orange), II (green), III (blue) and IV (purple). e Key inputs onto the LHb that contribute to the encoding of unpredicted and predicted aversive and appetitive stimulus.