Processing of aversive stimuli: circuitry between the laterodorsal tegmental nucleus, the habenula, and dorsal and median raphe nuclei

Abstract

The habenula (Hb) is an epithalamic structure differentiated into medial (MHb) and lateral habenula (LHb). The LHb plays a key role in encoding disappointments and expectation of punishments, whereas the MHb-interpeduncular nucleus (IP) axis is critically involved in the mediation of the aversive effects of nicotine. Consistent with a key role in processing aversive information, the Hb has been implicated in a broad array of functions and pathologic conditions, notably in mechanisms of stress, nicotine consumption and in the pathophysiology of anxiety and depression. So far, the vast majority of research on the Hb has focused on its role in regulating monoaminergic nuclei. Thus, there is now ample evidence that MHb/LHb are robustly interconnected with dopamine and serotonin nuclei by a complex network of direct and indirect connections. In contrast, little is known about the relations of MHb/LHb with cholinergic cell groups such as the laterodorsal tegmental nucleus (LDTg). The LDTg is an important component of the ascending reticular system and has been implicated in mechanisms of fear/anxiety and the promotion of emotional arousal under adverse conditions. In order to clarify Hb connections with the LDTg, the main objective of the present project is to investigate in detail the topography and neurochemical signature of the direct projections between LHb e LDTg, as well as the circuits that interconnect the LDTg with midline structures such as the MHb-IP axis, the dorsal/median raphe nuclei, and the septum. For this purpose we will combine tract tracing methods with immunohistochemical/in situ hybridization techniques and genetic approaches. (AU)