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The mammalian lateral habenular complex-projection and back projection to the ventral tegmental area, the center of the reward system

Petzel, A;

Zusammenfassung Mammalian behavior largely depends on the individual and its reaction to a stimulus. In principle it is based on two systems, either deeply enrooted reflex-type mechanisms or freely selected actions, which often in the broadest sense regulate homeostatic necessities. Such behaviors per se are emotionally neutral. To make an individual perform such psychologically indifferent actions nature has developed a specialized brain circuit, the reward system. It predominantly consists of the dopaminergic and serotoninergic midbrain nuclei and their major projection targets, the nucleus accumbens and the medial orbitofrontal cortex. Not the biological necessity, but the grandiose internal feeling after such homeostatic activities like feeding or sexual intercourse makes individuals to perform such acts over and over. For the purpose of counterregulation, there must be an opposing system, which spoils hedonic feelings in unsatisfactory situations. This anti-reward-system in the vertebrate brain is represented by the habenula nucleus and its medial (MHb) and especially in its lateral (LHb) complexes. This processing center for multitudinous inputs evaluates a given situation and appropriately decreases dopaminergic activity in the ventral tegmental area (VTA) which leads to an omission of hedonic feelings. To complete the anti-reward signaling cycle, there must be some type of feedback from the VTA to the LHb. In the present investigation the connections from the LHb to the VTA, the back projection from the VTA to the LHb, and the direct and indirect projections from the LHb to the VTA were analyzed in the rat. Anterograde and especially retrograde tracing in combination with immunocytochemistry and in-situ hybridization experiments of markers for individual transmitter systems disclosed that most neurons in the LHb were glutamatergic and their axons mainly terminated on GABAergic neurons of the ventral midbrain. Anterior and posterior parts of the VTA and the rostromedial tegmental nucleus (RMTg) receive topographically distinct afferents from the LHb. The back projection from the VTA to the LHb is not predominantly GABAergic, as thought previously, but dopaminergic neurons in the VTA substantially contribute to this pathway. The habenula often is considered as relay station for a reciprocal link between limbic and midbrain areas, while it is not clear, whether these connections are unequivocally reciprocal. Our data indicate that this actually is the case. Furthermore, we have shown that there are two pathways from the LHb to the VTA: a direct projection from the LHb to the VTA and an indirect one from the LHb via the RMTg to the VTA, which may subserve different biological purposes.