The question of how sensory feedback shapes learned behavior is fundamental to understanding how we acquire and loose skills. In passerine birds such as zebra finches, song development and adult song maintenance critically depend on auditory feedback, and the study of these gives insight into the mechanisms for learning in the context of complex sensorimotor behaviors. Recent evidence highlights surprising state-dependent processing in the birdsong system, showing that the organization of the motor program during singing and the expression of auditory activity is regulated by the activity of the cholinergic basal forebrain (BF), including effects on HVc neurons. Using cellular, systems, and behavioral analysis, this project explores the role of behavioral state in sensorimotor learning in the birdsong system. The first experiment will characterize the role of BF in regulating singing. Singing behavior will be characterized after disruption of BF by lesion or electrical stimulation. BF manipulations will be combined with other lesions designed to manipulate auditory feedback, testing if BF contributes to feedback mediated learning. Single cell recordings during singing will provide insight into how compensatory responses including auditory feedback signals are transmitted throughout the song system. The second experiment will elucidate the synaptic mechanisms of cholinergic activity, manipulating both the cholinergic milieu and fictive output and auditory input in an in vitro brain slice preparation of HVc. Finally, cholinergic properties of HVc cells recorded in anesthetized birds will be assessed to relate the in vivo and in vitro results. Cholinergic activity has long been associated with states of heightened perceptual attention, but its role in sensorimotor learning has never been extensively analyzed. This project will test the hypothesis that cholinergic activity regulates sensorimotor learning. Positive results may also contribute to an understanding of the relation between basal forebrain degeneration and language disturbances in humans.

R01MH059831

1999-05-05

2010-12-31