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.

National Institute of Health (NIH)
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Auditory System Study Section (AUD)
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Cyr, Janet
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University of Maryland College Park
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College Park
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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

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