Coleoid cephalopods (octopuses, squid, and cuttlefish) have the largest central nervous systems and the greatest brain-to-body mass ratios of all the invertebrates. While many big-brained animals, such as primates and corvids, survive for decades, coleoid cephalopods are unusually short-lived. Most cephalopods live for only a few years at most. In coleoids, lifespan and reproduction are actively controlled by the optic glands, a pair of neuroendocrine organs that are functionally analogous to the vertebrate pituitary gland. To understand the mechanisms underlying longevity across big-brained invertebrates and vertebrates, I propose to characterize the neurochemical organization of the optic glands. Aim 1 will rigorously characterize the neurochemical organization of the optic gland of O. bimaculoides, a commonly studied semelparous octopus. Results from this Aim will reveal 1) whether neuropeptide-, steroid-, and catecholamine-producing cells are distinct or overlapping and 2) how neurochemical territories change as a result of mating. test the evolutionary conservation of optic gland ligands between semelparous and iteroparous cephalopods. Aim 2 will provide long-overdue insight on the neurochemical basis of the iteroparous optic gland and test the evolutionary conservation of optic gland ligands between semelparous and iteroparous cephalopods. Overall, this proposal will establish a new comparative framework for studying control of reproduction and lifespan.