Basal ganglia-cortical (BG) circuits are critically involved in normal motor behavior (especially sequenced behavior) and learning, in motivation and reward, and in numerous neuropsychiatric disorders, including schizophrenia, drug addictions, and Parkinson's disease. Despite the importance of these pathways, much remains to be learned about their function, in part because of the complexity in many animals both of the circuits and of the behaviors they control. Songbirds provide a potentially powerful small animal model for providing insights into mechanisms of BG action, because their relatively simple learned vocal behavior, song, is mediated by a discrete set of brain areas that includes a specialized BG circuit. It is well-established that this 'anterior forebrain pathway' (AFP) is critical for vocal learning and adult vocal plasticity, and it has been suggested that it contributes motor variability necessary for motor exploration and/or adaptive signals to guide song learning. However, most in vivo neurophysiological studies of the AFP have focused on its pallial output nucleus 'LMAN'. Thus, relatively little is known about other components of the circuit in behaving birds and about whether and how neural firing during singing changes as it traverses the loop. In this proposal we aim to test the hypothesis that there is a gradual transformation of the encoding of song- related activity through the AFP that is likely to be critical both to adult plasticity and to song learning. We will accomplish this by first recording from multiple cell types in the striato-pallidal portion of the AFP, Area X, as well as from LMAN, in awake, behaving adult zebra finches during singing, and analyzing how the activity in these two regions co-varies, and how it relates to song (Aim 1). We will then manipulate activity in Area X, either with pharmacological inhibition or with lesions, and assess the effects on LMAN firing and on song (Aim 2). This will test ideas from Aim 1 about processing through the circuit, and should also shed light on why disruptions of Area X and LMAN have strikingly different effects on song plasticity. Finally, we will analyze Area X and LMAN firing in young birds in the process of sensorimotor learning, when song still varies in its sequence and syllable stability (Aim 3). By studying these circuits before learning is complete and then following the neural changes as song is crystallized, we should gain further insights into how activity evolves in this circuit and how it relates to the accuracy and stability of song. This will also provide tests of the hypotheses that signals in the AFP contribute variability and/or instruction. Analyses of our simple circuit have the potential to elucidate very general rules about how BG circuits function, both normally and in the many diseases in which these structures are involved. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH055987-13
Application #
7459097
Study Section
Sensorimotor Integration Study Section (SMI)
Program Officer
Simmons, Janine M
Project Start
1996-07-01
Project End
2011-06-30
Budget Start
2008-07-01
Budget End
2009-06-30
Support Year
13
Fiscal Year
2008
Total Cost
$318,792
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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