Birdsong is an excellent model for understanding the neural basis of complex vocal behavior, like human speech. Songbirds naturally learn and produce their song, and like human speech, the learning process depends on hearing. Our long-term goal is to understand the neural mechanisms of song production. As a beginning, this proposal considers the role played by the telencephalic nucleus HVc in zebra finches, which produce one song with high stereotypy throughout life. HVc is likely to participate in driving song production: it is required for singing, its neurons display premotor and patterned activity during song production, and it is poised anatomically to influence the output of the syrinx, the avian vocal organ. Furthermore, studies of HVc in vivo have implicated it as a pattern generator for song. The experiments described here propose to develop a slice preparation of HVc that can be induced to produce activity in vitro that mimics the rhythmic activity observed during song production in vivo. Recent indirect evidence shows that patterned activity can be elicited in brain slice preparations of HVc; the goal here is to directly observe the spiking activity, and to induce it reliably. Specifically, extracellular recordings will be used to monitor the spiking patterns of HVc cells in vitro in response to brief high frequency stimuli, application of neuromodulators, or both. If patterned activity results, we will analyze it for stereotypy and similarity to the song of the bird from which the brain slice was made. The proposal is highly exploratory because it aims to discover the conditions under which rhythmic, singing-related activity can be induced in HVc in vitro. This approach will at least clarify the extent to which HVc is capable of generating rhythmic activity in isolation. If these experiments yield reliable rhythmic activity related to song, then this will be a strong candidate for a preparation of """"""""fictive singing."""""""" Such a preparation would provide one of the few vertebrate examples of pattern generation in vitro, claim the first instance of in vitro pattern generation for vocal behavior within the telencephalon, and it would form a basis for future mechanistic investigations of rhythmic activity in HVc, song production, and more generally the motor control of sequenced and patterned motor outputs. This knowledge would be applicable to understanding the mechanisms governing speech production in humans, and enhance the understanding of speech, how it is learned, and its pathologies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21MH068530-02
Application #
6873636
Study Section
Sensorimotor Integration Study Section (SMI)
Program Officer
Vicentic, Aleksandra
Project Start
2004-08-01
Project End
2007-05-31
Budget Start
2005-06-01
Budget End
2007-05-31
Support Year
2
Fiscal Year
2005
Total Cost
$151,600
Indirect Cost
Name
University of Washington
Department
Zoology
Type
Schools of Arts and Sciences
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
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Meitzen, John; Thompson, Christopher K; Choi, Heejung et al. (2009) Time course of changes in Gambel's white-crowned sparrow song behavior following transitions in breeding condition. Horm Behav 55:217-27
Meitzen, John; Thompson, Christopher K (2008) Seasonal-like growth and regression of the avian song control system: neural and behavioral plasticity in adult male Gambel's white-crowned sparrows. Gen Comp Endocrinol 157:259-65
Sizemore, Max; Perkel, David J (2008) Noradrenergic and GABA B receptor activation differentially modulate inputs to the premotor nucleus RA in zebra finches. J Neurophysiol 100:8-18
Meitzen, John; Moore, Ignacio T; Lent, Karin et al. (2007) Steroid hormones act transsynaptically within the forebrain to regulate neuronal phenotype and song stereotypy. J Neurosci 27:12045-57
Meitzen, John; Perkel, David J; Brenowitz, Eliot A (2007) Seasonal changes in intrinsic electrophysiological activity of song control neurons in wild song sparrows. J Comp Physiol A Neuroethol Sens Neural Behav Physiol 193:677-83
Solis, Michele M; Perkel, David J (2006) Noradrenergic modulation of activity in a vocal control nucleus in vitro. J Neurophysiol 95:2265-76
Solis, Michele M; Perkel, David J (2005) Rhythmic activity in a forebrain vocal control nucleus in vitro. J Neurosci 25:2811-22