Early experiences of the world are fundamental in shaping the structural and functional organization of the brain. A brain region that particularly relies on sensory experience during a critical period of development is the auditory cortex (ACX), an area critically involved in language acquisition. Hearing impairments early in life that remain untreated, result in irreversible, abnormal organization of ACX and lead to lifelong speech and language disabilities. The functional architecture of the ACX in adult mammals has been widely studied, and it is evident that individual auditory neurons are tuned to complex features of acoustic stimuli, but the fine-scale organization of the ACX and its development remains unknown. In this proposal, I plan to characterize the functional responses of ACX neurons in different cortical layers to simple tonal stimuli and complex vocalization components during early hearing development. Furthermore, I will test how abnormal auditory experiences during development alter the emergence and functional spatial organization of neuronal responses to sound. To accomplish this, I will use in vivo two-photon calcium imaging to optically record fluorescence changes of ACX neurons in response to acoustic stimuli and will use computational methods to describe how response parameters of individual neurons evolve with hearing development (response amplitude, selectivity, bandwidth, sound threshold, frequency tuning) as well as how neuronal networks change as they mature (best frequency variability, signal correlations, and noise correlations). My proposed research using in vivo two-photon microscopy will advance our understanding of the critical changes that occur during hearing acquisition and maturation of ACX, and will reveal which particular circuits in subplate, thalamorecipient layer 4, and supragranular layers 2/3 are changing with normal and altered early experiences. A greater understanding of the complexity of ACX development and its dependence on environmental input will provide insight into the critical relationship between sensory input and cortical organization, as well how this system reorganizes based on what stimuli are perceived to be meaningful. My findings will offer a rich foundation for the continued study of developmental hearing disorders by providing insight into how early deficits in peripheral auditory processing can cause altered wiring of specific cortical circuits and permanent complications in hearing and language processing. The more we understand how a normal brain responds to and processes auditory input, the more suited we are to detect and correct abnormalities early in development.
In this study, I will characterize the functional responses of ACX neurons in different cortical layers to simple tonal stimuli and complex vocalizations components during early hearing development. Furthermore, I will test how abnormal auditory experiences during development alter the emergence and functional spatial organization of neuronal responses to sound stimuli. My proposed research using in vivo two-photon calcium imaging will advance our understanding of the critical changes that occur during hearing acquisition and maturation of ACX, and will reveal which particular circuits in subplate, thalamorecipient layer 4, and supragranular layers 2/3 are changing with normal and altered early experiences.
