There is a fundamental gap in understanding how plasticity in the nervous system supports the development of communication skills in healthy individuals. Specifically, it is poorly understood how experience with vocalizations affects maturation of the central auditory system crucial to auditory-vocal integration. It is therefore challenging to identify the processes underlying developmentally delayed or impaired perception of speech. The acquisition of a songbird's song parallels human speech learning at the behavioral as well as the neuronal level and thus provides unique opportunities to investigate the neural mechanisms of learning and memory. The long-term goal of the principal investigator is to determine the cellular and systems-level mechanisms through which birds acquire, store and retrieve auditory memories. The objective of the current proposal is to determine how early auditory experience modifies neuronal systems underlying memory for vocalizations. The central hypothesis, formulated on the basis of preliminary data, is that development of hemispheric dominance is required for successful acquisition of auditory memory. This hypothesis will be tested by pursuing two specific aims, which will determine: 1) How auditory experience alters the neuronal response to conspecific vocalizations throughout development; and 2) The neural systems mechanism underlying the formation of lateralized circuits for memory. In the first aim, manipulations of the early auditory environment will be combined with analysis of song learning and quantification of stimulus-dependent neuronal activation and the Blood Oxygenation Level Dependent (BOLD) response. Each of these methods, including the use of commercially available antibodies and freely available song and image analysis software, has previously been established in songbirds. Strong preliminary data indicate feasibility to perform the proposed studies in the applicant's laboratory. In the second aim, pharmacological inhibition of neuronal activity will be used at critical moments during the song learning process; subsequent song imitation will be quantified to demonstrate effects of treatment on the strength of learning. In previous publications from the applicant, pharmacological interventions have been combined with measures of song imitation, which, in combination with data from pilot studies, provides evidence for the feasibility of the proposed studies in the PI's lab. The approach is innovative because this work brings together research on human language development and birdsong learning, through its emphasis on lateralization of the underlying neural substrates. The proposed research is significant, because the data acquired may inform the interpretation of imaging studies in humans, where systems, cellular and molecular analyses of cognitive development are not possible. Understanding the normal development of auditory perception will allow us to further investigate auditory-vocal learning at the cellular and molecular level and, ultimately, to identify candidate mechanisms for disorders of auditory perception and language acquisition.

Public Health Relevance

Language learning in human infants starts with the successful acquisition of auditory memories; language disorders or delays are often characterized by abnormal lateralization of function and frequently found in patients diagnosed with auditory processing disorder (APD), affecting 2-3% of children, or autism, affecting ~1% of children. The proposed research is relevant to public health because data will be acquired at the cellular and systems-level in the songbird model, currently the only available model system for vocal learning. This will ultimately lead to a better understanding of neurological disorders in which speech perception is developmentally delayed or impaired; the proposed research is thus relevant to NIH's mission pertaining to children achieving their full potential.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
1R15HD085143-01A1
Application #
9096296
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Alvarez, Ruben P
Project Start
2016-03-01
Project End
2019-02-28
Budget Start
2016-03-01
Budget End
2019-02-28
Support Year
1
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Wellesley College
Department
Neurosciences
Type
Schools of Arts and Sciences
DUNS #
076572965
City
Wellesley
State
MA
Country
United States
Zip Code