The major goal of these studies is to understand how different vocal patterns are generated at the level of individual vocal neurons and intemeurons and at the circuit level comprising ensembles of these neurons. In Xenopus laevis secretion of steroid hormones (androgens and estrogens) is essential both for establishing sex differences in vocal output during development and for evoking the behaviors themselves in adulthood. A related aim of these studies is thus to determine how these differences are generated - either during development or in adulthood - under the influence of gonadal steroids. We will begin with the vocal motor neurons themselves and then move on to focus on their afferents, the elements that comprise pattern generation and finally the activation of these elements by sexual state and behavioral context. These issues will be approached using a combination of techniques and preparations: intracellular recordings (including patch-clamp), calcium iimaging, laryngeal nerve recordings from vocalizing frogs, the isolated whole brain and larynx and the hindbrain slice. Cells that participate in vocal production will be identified using a combination of anatomical (tracing in the isolated whole brain) and electrophysiological methods. These kinds of effects are central to an understanding of male- and female- clinical disorders; hormone-directed cell development underlies maliganancies of prostate and breast, disorders of secondary sexual differentiation such as androgen-insensitivity and pseudohemaphodism and at least some aspects of the establishment of gender identity. Estrogen, which regulates the strength of the vocal synapse in this system, has similar effects in mammalian brain that are believed to subserve the neuroprotective effects of estrogen in Alzheimer's disease. An understanding of mechanisms underlying endocrine regulation of synaptic efficacy may provode useful points for intervention in patients with impaired cognition.
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