The perception of speech and language requires normal functioning of the auditory cortex. Abnormal brain function, due to alterations in wiring, i thought to be responsible for many disorders such as cerebral palsy, schizophrenia, autism, and tinnitus. Correction of these disorders would seem to require the ability to rewire the brain. The young brain can adjust its connectivity depending on external inputs especially during early """"""""critical periods"""""""". For example early experience with speech is required for the normal development of the brain, and abnormal experience prevents normal development. Replacement of sensory experience after the critical period does not lead to successful functional recovery. We are investigating the ability of the young cortex to establish and adjust its wiring in response to experience. We characterizing circuits throughout development, and identify and manipulate key neuronal populations that regulate development and plasticity. Our work focuses on the auditory cortex a region crucial for human language communication. The developing cerebral cortex contains an enigmatic population of neurons called subplate neurons. Remarkably, these neurons are largely absent in adults highlighting their specialized role in development. However, despite their importance, detailed knowledge about subplate neurons and their role(s) are sparse. We hypothesize that subplate neurons provide both a substrate to establish a template of intra-cortical organization and that early spontaneous activity and sensory experience shape the functional and synaptic organization of subplate. 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) What is the functional organization of the distinct subcircuits within subplate? 2) What is the role of subplate and early sensory activity in patterning of intra-cortical circuits? 3 What is the role of subplate and early sensory activity in sculpting the functional organization 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.

Public Health 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, and the proposed experiments elucidate the microcircuitry and functional role of subplate neurons in providing a template for future cortical organization by physiological and imaging methods. These studies lay the groundwork for better understanding of auditory cortical development, add to knowledge of normal development in children and to understanding causes of neurodevelopmental disorders such as cerebral palsy, epilepsy, autism, and schizophrenia.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
2R01DC009607-06A1
Application #
8697856
Study Section
Auditory System Study Section (AUD)
Program Officer
Cyr, Janet
Project Start
2008-07-01
Project End
2019-03-31
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
6
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Maryland College Park
Department
Biology
Type
Earth Sciences/Resources
DUNS #
City
College Park
State
MD
Country
United States
Zip Code
20742
Wess, Jessica M; Isaiah, Amal; Watkins, Paul V et al. (2017) Subplate neurons are the first cortical neurons to respond to sensory stimuli. Proc Natl Acad Sci U S A 114:12602-12607
Deng, Rongkang; Kao, Joseph P Y; Kanold, Patrick O (2017) Distinct Translaminar Glutamatergic Circuits to GABAergic Interneurons in the Neonatal Auditory Cortex. Cell Rep 19:1141-1150
Meng, Xiangying; Winkowski, Daniel E; Kao, Joseph P Y et al. (2017) Sublaminar Subdivision of Mouse Auditory Cortex Layer 2/3 Based on Functional Translaminar Connections. J Neurosci 37:10200-10214
Nagode, Daniel A; Meng, Xiangying; Winkowski, Daniel E et al. (2017) Abnormal Development of the Earliest Cortical Circuits in a Mouse Model of Autism Spectrum Disorder. Cell Rep 18:1100-1108
Henschke, Julia U; Oelschlegel, Anja M; Angenstein, Frank et al. (2017) Early sensory experience influences the development of multisensory thalamocortical and intracortical connections of primary sensory cortices. Brain Struct Funct :
Francis, Nikolas A; Kanold, Patrick O (2017) Automated Operant Conditioning in the Mouse Home Cage. Front Neural Circuits 11:10
Winkowski, Daniel E; Nagode, Daniel A; Donaldson, Kevin J et al. (2017) Orbitofrontal Cortex Neurons Respond to Sound and Activate Primary Auditory Cortex Neurons. Cereb Cortex :
Viswanathan, Sarada; Sheikh, Aminah; Looger, Loren L et al. (2016) Molecularly Defined Subplate Neurons Project Both to Thalamocortical Recipient Layers and Thalamus. Cereb Cortex :
Mordel, Jérôme; Sheikh, Aminah; Tsohataridis, Simeon et al. (2016) Mild systemic inflammation and moderate hypoxia transiently alter neuronal excitability in mouse somatosensory cortex. Neurobiol Dis 88:29-43
Muralidharan, Sukumaran; Dirda, Nathaniel D A; Katz, Elizabeth J et al. (2016) Ncm, a Photolabile Group for Preparation of Caged Molecules: Synthesis and Biological Application. PLoS One 11:e0163937

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