Patients with basal ganglia disease or injury suffer from a wide range of motor deficits, including deficiencies in the ability to correct movement errors and learn new movements. Although we know that the basal ganglia is important for learning, we still know relatively little of how it contributes to motor plasticity, hindering the understanding and treatment of deficits after neurological disorders and stroke. In particular, it s not clear how it acts to guide learned adjustments of motor output in response to sensory error signals. It is also unclear whether it plays a major function in transferring learning to new contexts ("generalization"). Finally, although dopamine signaling has long been proposed as being important for learning, its role in learning and generalization remains poorly understood. The proposed project will leverage an animal model (the songbird) uniquely suited for addressing this knowledge gap. Bengalese finches exhibit a complex learned motor behavior (song) maintained via sensorimotor error correction. Their song consists of a series of rapidly produced vocal gestures, or "syllables", which they learn as juveniles from adult tutors, much as human infants learn to speak from parents. A network of interconnected nuclei known as the song system enables song learning and production. The basal ganglia nucleus Area X forms an integral part of this system and has many similarities and homologies to the human basal ganglia. Our lab has developed a novel behavioral paradigm to evoke adaptive vocal changes and generalization behavior in Bengalese finches by altering auditory feedback. This paradigm will allow us to pursue the long-term objective of understanding in detail the basal ganglia's and dopamine's role in learning and generalization. Our central hypothesis is that vocal learning is mediated by dopamine signaling in the basal ganglia and that change in basal ganglia firing patterns during learning underlie learned changes in song. This hypothesis will be tested through two Aims.
In Aim 1, it will be determined how complete lesions of Area X, and selective lesions of the dopamine neurons projecting to Area X, affect learning ability.
In Aim 2 Area X neurons will be recorded in singing birds while driving learning. Changes in Area X neural activity will be related to the changes in vocal output. Two aspects of learning will be investigated: adaptive modification of the specific gestures during which sensory errors occurred, and generalization of this learning to other gestures. Learning will be driven by altering auditory feedback on specific vocalizations within the song and observing how the bird changes both the altered and unaltered vocalizations to compensate. Together, these studies will yield a detailed characterization of the basal ganglia's role in motor learning.

Public Health Relevance

Patients with basal ganglia injury, disease or dysfunction suffer from a range of symptoms including motor learning deficits, but we know relatively little about how the basal ganglia (and the dopamine that influences its processing) are involved in changing learned motor behavior in response to sensory error signals. This research proposal will reveal the basal ganglia's role in error-corrective learning by driving this process in the songbird, a model organism whose basal ganglia shares many features with that of humans. This will increase our understanding of how the basal ganglia contributes to different forms of motor plasticity and may improve our understanding of how to treat basal ganglia pathologies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31NS089406-01A1
Application #
8835956
Study Section
Special Emphasis Panel (ZRG1-F02B-D (20))
Program Officer
Chen, Daofen
Project Start
2014-09-15
Project End
2016-09-14
Budget Start
2014-09-15
Budget End
2015-09-14
Support Year
1
Fiscal Year
2014
Total Cost
$42,676
Indirect Cost
Name
Emory University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322