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

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC009607-04
Application #
8246953
Study Section
Special Emphasis Panel (ZRG1-IFCN-B (02))
Program Officer
Freeman, Nancy
Project Start
2009-04-01
Project End
2014-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
4
Fiscal Year
2012
Total Cost
$353,355
Indirect Cost
$113,775
Name
University of Maryland College Park
Department
None
Type
Schools of Arts and Sciences
DUNS #
790934285
City
College Park
State
MD
Country
United States
Zip Code
20742
Watkins, Paul V; Kao, Joseph P Y; Kanold, Patrick O (2014) Spatial pattern of intra-laminar connectivity in supragranular mouse auditory cortex. Front Neural Circuits 8:15
Meng, Xiangying; Kao, Joseph P Y; Kanold, Patrick O (2014) Differential signaling to subplate neurons by spatially specific silent synapses in developing auditory cortex. J Neurosci 34:8855-64
Kanold, Patrick O; Nelken, Israel; Polley, Daniel B (2014) Local versus global scales of organization in auditory cortex. Trends Neurosci 37:502-10
Winkowski, Daniel E; Bandyopadhyay, Sharba; Shamma, Shihab A et al. (2013) Frontal cortex activation causes rapid plasticity of auditory cortical processing. J Neurosci 33:18134-48
Winkowski, Daniel E; Kanold, Patrick O (2013) Laminar transformation of frequency organization in auditory cortex. J Neurosci 33:1498-508
Viswanathan, Sarada; Bandyopadhyay, Sharba; Kao, Joseph P Y et al. (2012) Changing microcircuits in the subplate of the developing cortex. J Neurosci 32:1589-601
Tolner, Else A; Sheikh, Aminah; Yukin, Alexey Y et al. (2012) Subplate neurons promote spindle bursts and thalamocortical patterning in the neonatal rat somatosensory cortex. J Neurosci 32:692-702
Postma, Friso; Liu, Cheng-Hang; Dietsche, Caitlin et al. (2011) Electrical synapses formed by connexin36 regulate inhibition- and experience-dependent plasticity. Proc Natl Acad Sci U S A 108:13770-5
He, Kaiwen; Lee, Angela; Song, Lihua et al. (2011) AMPA receptor subunit GluR1 (GluA1) serine-845 site is involved in synaptic depression but not in spine shrinkage associated with chemical long-term depression. J Neurophysiol 105:1897-907
Bandyopadhyay, Sharba; Shamma, Shihab A; Kanold, Patrick O (2010) Dichotomy of functional organization in the mouse auditory cortex. Nat Neurosci 13:361-8

Showing the most recent 10 out of 13 publications