ReviewThe role of lateral habenula-dorsal raphe nucleus circuits in higher brain functions and psychiatric illness

•Lateral habenula (LHb) and dorsal raphe nucleus have close anatomical connections.•LHb-raphe circuits influence cognition, reward, pain, sleep and circadian rhythms.•Abnormal LHb-raphe activity may disrupt these functions in psychiatric disorders.•Increased LHb activity may contribute especially to the symptoms of depression.

Serotonergic neurons in the dorsal raphe nucleus (DRN) play an important role in regulation of many physiological functions. The lateral nucleus of the habenular complex (LHb) is closely connected to the DRN both morphologically and functionally. The LHb is a key regulator of the activity of DRN serotonergic neurons, and it also receives reciprocal input from the DRN. The LHb is also a major way-station that receives limbic system input via the stria medullaris and provides output to the DRN and thereby indirectly connects a number of other brain regions to the DRN. The complex interactions of the LHb and DRN contribute to the regulation of numerous important behavioral and physiological mechanisms, including those regulating cognition, reward, pain sensitivity and patterns of sleep and waking. Disruption of these functions is characteristic of major psychiatric illnesses, so there has been a great deal of interest in how disturbed LHb-DRN interactions may contribute to the symptoms of these illnesses. This review summarizes recent research related to the roles of the LHb-DRN system in regulation of higher brain functions and the possible role of disturbed LHb-DRN function in the pathogenesis of psychiatric disorders, especially depression.