Immunohistochemistry and neurochemistry of the habenulo-interpeduncular connection after partial developmental depletion of habenular cholinergic neurons in the rat.

The habenulo-interpeduncular system of the rat constitutes an interesting model to address quantitatively problems related to synaptogenesis and to the interactions between neuronal populations after selective alteration of these elements during development. In the present study this has been achieved by experimentally reducing, through gestational treatment with methylazoxymethanol acetate (MAM), the population of cholinergic neurons of the medial habenula which projects to the interpeduncular nucleus. Immunohistochemical analysis gave evidence that the topographical localization of the cholinergic and the substance P-containing populations in the medial habenula was not altered by MAM treatment. Furthermore, the topographical distribution of cholinergic fibers and terminals in the interpeduncular nucleus, which reflects the habenulo-interpeduncular projection as well as cholinergic projections coming from different sources, was substantially preserved. The same was also true concerning the terminal distribution of substance P in the interpeduncular nucleus. Quantitative radioassays demonstrated a sizable decrease of overall ChAT activity in both the habenulae and the interpeduncular nucleus. By comparison of 1 month-old and 3 month-old animals it appeared that this effect was partially reversed with age in the interpeduncular nucleus.