The perception of speech and language requires normal functioning of the auditory cortex. Injury to the developing brain can lead to deficits in speech and language perception that originate from altered auditory cortex function. To understand how these deficits develop and to devise novel treatment approaches for early injuries one has to understand the functional development and plasticity of auditory cortex. During early times in development, additional neuronal circuits are present in all areas of the developing cortex that are absent in the adult cortex. These circuits are formed by subplate neurons. Subplate neurons play a key role in the functional maturation of thalamocortical synapses and inhibitory circuits as well as plasticity during the critical period when sensory experience can sculpt cortical circuits. Despite this demonstrated importance of subplate neurons, it is unknown how these neurons are integrated in the developing cortical circuit, how they respond to sound, and how they influence auditory cortical development. It is our central hypothesis that subplate neurons aid in setting up cortical maps, such as the tonotopic map in auditory cortex, by controlling the activity dependent maturation of thalamocortical and inhibitory circuits. Since these maps are important for the processing of sound information, understanding their formation and plasticity is essential to understanding the effects of early injuries. To address these fundamentally important issues we propose a series of in vivo and in vitro experiments in mouse auditory cortex using a combination of electrophysiological and imaging techniques. 1) To determine the functional connectivity of subplate neurons in auditory cortex. 2) To determine the response characteristics of subplate neurons to sound. 3) To determine how subplate neurons guide thalamocortical maturation and how subplate neurons contribute to the columnar architecture of auditory cortex Collectively these experiments will provide the fundamental framework of understanding development and plasticity of auditory cortex by elucidating the function of a previously ignored central component of auditory cortex development. 1

Public Health Relevance

Relevance to public health: Injury to the developing brain leads to deficits in speech and language perception that might originate in altered function of the primary auditory cortex. Such injury in early life damages subplate neurons, which are critical for normal development. The proposed experiments for the first time elucidate the connectivity and functional role of subplate neurons in the developing auditory cortex by physiological and imaging methods and thus they lay the groundwork for better understanding of auditory cortical development. Results should also add to knowledge of normal development in children and to understanding causes of neurodevelopmental disorders such as cerebral palsy, epilepsy, and schizophrenia. 1

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
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Special Emphasis Panel (ZRG1-IFCN-B (02))
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Freeman, Nancy
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University of Maryland College Park
Schools of Arts and Sciences
College Park
United States
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