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.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
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Integrative, Functional and Cognitive Neuroscience 8 (IFCN)
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Mitler, Merrill
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Columbia University (N.Y.)
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New York
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Barkan, Charlotte L; Kelley, Darcy B; Zornik, Erik (2018) Premotor Neuron Divergence Reflects Vocal Evolution. J Neurosci 38:5325-5337
Kelley, Darcy B; Elliott, Taffeta M; Evans, Ben J et al. (2017) Probing forebrain to hindbrain circuit functions in Xenopus. Genesis 55:
Hall, Ian C; Woolley, Sarah M N; Kwong-Brown, Ursula et al. (2016) Sex differences and endocrine regulation of auditory-evoked, neural responses in African clawed frogs (Xenopus). J Comp Physiol A Neuroethol Sens Neural Behav Physiol 202:17-34
Albersheim-Carter, Jacob; Blubaum, Aleksandar; Ballagh, Irene H et al. (2016) Testing the evolutionary conservation of vocal motoneurons in vertebrates. Respir Physiol Neurobiol 224:2-10
Leininger, Elizabeth C; Kitayama, Ken; Kelley, Darcy B (2015) Species-specific loss of sexual dimorphism in vocal effectors accompanies vocal simplification in African clawed frogs (Xenopus). J Exp Biol 218:849-57
Sweeney, Lora B; Kelley, Darcy B (2014) Harnessing vocal patterns for social communication. Curr Opin Neurobiol 28:34-41
Leininger, Elizabeth C; Kelley, Darcy B (2013) Distinct neural and neuromuscular strategies underlie independent evolution of simplified advertisement calls. Proc Biol Sci 280:20122639
Hall, Ian C; Ballagh, Irene H; Kelley, Darcy B (2013) The Xenopus amygdala mediates socially appropriate vocal communication signals. J Neurosci 33:14534-48
Nasipak, Brian; Kelley, Darcy B (2012) Developing laryngeal muscle of Xenopus laevis as a model system: androgen-driven myogenesis controls fiber type transformation. Dev Neurobiol 72:664-75
Evans, B J; Greenbaum, E; Kusamba, C et al. (2011) Description of a new octoploid frog species (Anura: Pipidae: Xenopus) from the Democratic Republic of the Congo, with a discussion of the biogeography of African clawed frogs in the Albertine Rift. J Zool (1987) 283:276-290

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