Habenular and interpeduncularis nuclei: shared components in multiple-function networks

This paper reviews habenula (Hb) and interpeduncularis nucleus (IPN) literature from the perspective that the axial anatomy of Hb-IPN could be shared by numerous brain circuits that subserve diverse functions. The first section summarizes the major anatomical connections, showing that the axis is strategically positioned between key rostral structures and brainstem areas. Little is known about these connections as they relate to the heterogeneous Hb-IPN sub-nuclei. Insufficient understanding exists about ascending pathways in the fasiculus retroflexus, possible pineal gland connections with the Hb, serotonergic inputs, whether given pathways are excitatory or inhibitory, and interactions of neurotransmitter systems. Next reviewed are studies that implicate the Hb-IPN axis in a variety of brain functions and behaviors. These include nociception, learning and memory, motor activity, sexual and maternal behavior, stress, affective states (anxiety, depression, and reward phenomena), sleep, and eating and drinking behavior. I propose that these multiple functions arise because the Hb-IPN is a shared-component axis in the multiple circuits that subserve these different elements of behavior. More research is needed to test the possibility that the Hb-IPN provides a way for the brain to share circuitry, to explore the significance of the anatomical convergence of inputs to the lateral Hb, to map the circuitry of the subnuclei in Hb and IPN, to explore the interactions of the multiple neurotransmitter systems involved, to conduct studies in simpler animals, and to design experiments that will elucidate system properties of circuits that share the Hb-IPN axis.