The objective of this research are to determine how hormones cause structural changes in neurons during development, how such structural changes lead to changes in synaptic connections, and how changes in synaptic connections contribute to the assembly and dismantling of neuronal circuits underlying behavior. During metamorphosis of the moth, Manduca sexta ecdysteroid hormones control metamorphic events in the nervous system including neurogenesis, programmed neuron death, and the growth and regression of neuronal arbors. These parallel the effects of gonadal sex steroids on the developing vertebrate nervous system. During larval-pupal development of Manduca, ecdysteroids cause the dendrites of identified motorneurons (MNs) innervating abdominal proleg muscles to regress severely. Concomitantly, the proleg behaviors disappear. The hypothesis that regression of proleg MN dendrites causes the loss of synaptic inputs, thereby removing the MNs from behavioral circuits, will be tested during electrophysiological and anatomical studies of monosynaptic connections from afferent neurons and interneurons to the proleg MNs. Developmental changes in synaptic connections will be related to behavioral changes. Other MNs that do not regress, but which nonetheless show alterations in synaptic drive during this time, will be studied for comparison. Some experiments will use heterochromic mosaics, in which some neurons are retained in the larval stage while their synaptic partners become pupal. After pupation, some regressed proleg MNs die; the survivors are stimulated by ecdysteroids to regrow their dendritic arbors during adult development, and they take on new behavioral roles. Changes in synaptic inputs to these growing MNs will be studied, to compare with the findings during their regression. Finally, proleg MN regression and death can be induced by directly infusing ecdysteroids into the blood of larvae. Hormone infusions will be paired with treatment with inhibitors of DNA, mRNA or proteins synthesis, to determine the necessity of these synthetic events. One hypothesis to be tested is that MN regression and death are controlled by sequential critical periods of hormone action. In summary, the proposed experiments employ a range of approaches to gain a better understanding of how hormones influence neurons and neuronal circuits. These findings ought to be relevant to all animals in which hormones influence the developing nervous system.
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