DEVELOPMENT OF AMINE NEURONS AND ASSOCIATED BEHAVIORS

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Monoamine-containing neurons are universally present in vertebrate and invertebrate organisms. Serotonergic systems of neurons in particular have received wide attention because serotonin has been implicated in a variety of important behavioral processes and disorders: for example, sleep, locomotion, and mental illness. In the lobster Homarus americanus serotonin and octopamine induce sustained and opposite postures when injected into freely moving animals. These postures result from amines directing the readout of central motor programs for flexion (serotonin) and extension (octopamine). We have located the major sites of storage and release of these amines in lobsters, and have found individual neurons likely to contain serotonin that may plan a role in the generation of the postures. With this application, we propose to study the development of monoamine neurons, their targets, and postural control. The proposed studies fall into three major categories- (1) Neurogenesis: Using immunocytochemical and autoradiographic methods, we will study the developmental timetable for the appearance of serotonin and octopamine in neurons, and will determine the temporal sequence of differentiation of neurons destined to contain monoamines. We will also initiate studies of axonal outgrowth and cell lineages in lobster embryos. (2) Synaptogenesis and the development of function: Using ultrastructural, biochemical, and physiological methods, we will study when amine neurons begin to function in relation to the behaviors we are studying (the regulation of posture). Ultimately, we hope to correlate ultrastructural features of aminergic terminals with the onset of a functioning transmitter release mechanism. We will also ask when the motor programs for flexion and extension are (1) first sensitive to amines and (2) first responsive to activation of identified aminergic neurons. (3) Trophic influences during development: With these studies we will ask whether central and peripheral elements of the postural system develop normally in the absence of endogenous amines. Ultimately, we hope to ablate identified neurons involved in postural control; such techniques will allow us to study the influence of individual aminergic neurons on the ontogenesis of behavior. We believe that by focusing our attention on a small number of anatomically and functionally identifiable monoamine neurons and the relatively simple behavior in which they are involved, we can arrive at a better understanding of the morphological and physiological development of monoamine systems and their associated behaviors. We expect that generalities that emerge from these studies will be relevant in higher organisms as well.