Neurogenesis in subnuclei of the rat interpeduncular nucleus and medial habenula.

Development of the rat habenulo-interpeduncular system is of interest because of its highly ordered adult structure, including seven subnuclei within the interpeduncular nucleus (IPN), localization of synapses of different types and medial habenular (MH) sites of origin within the subnuclei, and differential localization of neurochemicals amongst the subnuclei. In order to further investigate the mechanisms by which these features are produced, the birthdays of neurons within IPN and MH were investigated. All IPN neurons were formed on embryonic days (E) 12 to 16. Birthdays varied for the subnuclei of IPN with the earliest being the serotonin containing apical subnucleus (p less than 0.0001) and the latest being the rostral subnucleus (p less than 0.0001). Rostral lateral and lateral subnuclei were approximately simultaneous with apical, and the intermediate and central subnuclei, related to each other in a number of other ways, had simultaneous birthdays earlier than the rostral subnucleus (p less than 0.0001) and later than the other subnuclei (p less than 0.0001). The medial habenula was found to consist of three regions, termed medial, lateral and dorsal, whose neurons undergo their final mitoses on E15-16, 16-17 and 17-18, respectively. These findings provide additional support for the validity of IPN subnuclei as currently delineated. They suggest mechanisms of development which involve early interactions between specific groups of MH neurons and specific groups of IPN neurons. It is proposed that a sequence of several control mechanisms operates during development to produce this complex system.