The proposed research aims at a mechanistic description of how complex motor sequences are generated and learned by brain circuits. Over the last decade, the songbird has emerged as an intriguing and approachable model system in which to pursue this problem. Songbirds learn their songs by trial-and-error experimentation, producing highly variable vocalizations as juveniles. By comparing their utterances to a memory of their tutor's song, their vocalizations gradually converge onto those of the tutor. The finished product is a stereotyped sequence of syllables that is driven by two forebrain motor nuclei, HVC, and RA (a motor cortex analogue). We believe that a key feature of the learning algorithm is the motor exploration that allows the bird to search for the right sound patterns. But what is the origin of this vocal exploration and how does it arise in the motor system? Aside from HVC, nucleus RA also receives excitatory projections from the lateral magnocellular nucleus of the nidopallium (LMAN), the output of a cortical-basal ganglia circuit. This circuit is not necessary for singing in adult birds, but is crucial for song learning. We recently found that inactivating LMAN largely abolishes the variability of juvenile song. Furthermore, we found that during singing, LMAN neurons that project to RA generate highly variable patterns of spikes and bursts. These observations led us to suggest that the LMAN input to RA directly drives vocal exploration in juvenile birds. We hope to build on these initial observations and address the following questions - How are the variable spike patterns in LMAN generated and how are they related to motor exploration? Since LMAN is the output of a well conserved basal ganglia circuit, understanding how this circuit contributes to variability in songbirds may shed light on motor learning in humans as well as speak to the role of the basal ganglia in motor function. Our goals are summarized in the following specific aims:
Specific Aim 1 : To determine the relative contribution of LMAN and HVC to the generation of juvenile song.
Specific Aim 2 : To characterize the correlation between LMAN firing and vocal output in the juvenile bird.
Specific Aim 3 : To determine where song variability is generated.
Specific Aim 4 : To measure the effect of LMAN input on the firing patterns of single RA neurons.

Public Health Relevance

Vocal exploration and learning in songbirds involve a basal ganglia-related (BG) circuit. The shared design of this avian circuit and mammalian BG circuitry implies that the neural mechanisms of song learning are likely to be directly relevant to mammalian BG and human disease. Disorders of BG circuitry lead to the impairments of serial processing and sequential behaviors observed in Parkinson's disease, schizophrenia, obsessive-compulsive disorder, Huntington's and the tardive syndromes.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC009183-05
Application #
8247157
Study Section
Sensorimotor Integration Study Section (SMI)
Program Officer
Shekim, Lana O
Project Start
2008-04-01
Project End
2013-06-30
Budget Start
2012-04-01
Budget End
2013-06-30
Support Year
5
Fiscal Year
2012
Total Cost
$295,042
Indirect Cost
$111,763
Name
Massachusetts Institute of Technology
Department
None
Type
Organized Research Units
DUNS #
001425594
City
Cambridge
State
MA
Country
United States
Zip Code
02139
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Okubo, Tatsuo S; Mackevicius, Emily L; Payne, Hannah L et al. (2015) Growth and splitting of neural sequences in songbird vocal development. Nature 528:352-7
Okubo, Tatsuo S; Mackevicius, Emily L; Fee, Michale S (2014) In vivo recording of single-unit activity during singing in zebra finches. Cold Spring Harb Protoc 2014:1273-83
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Goldberg, Jesse H; Fee, Michale S (2012) A cortical motor nucleus drives the basal ganglia-recipient thalamus in singing birds. Nat Neurosci 15:620-7
Goldberg, Jesse H; Farries, Michael A; Fee, Michale S (2012) Integration of cortical and pallidal inputs in the basal ganglia-recipient thalamus of singing birds. J Neurophysiol 108:1403-29
Veit, Lena; Aronov, Dmitriy; Fee, Michale S (2011) Learning to breathe and sing: development of respiratory-vocal coordination in young songbirds. J Neurophysiol 106:1747-65
Aronov, Dmitriy; Fee, Michale S (2011) Analyzing the dynamics of brain circuits with temperature: design and implementation of a miniature thermoelectric device. J Neurosci Methods 197:32-47
Aronov, Dmitriy; Veit, Lena; Goldberg, Jesse H et al. (2011) Two distinct modes of forebrain circuit dynamics underlie temporal patterning in the vocalizations of young songbirds. J Neurosci 31:16353-68

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