Tonotopy is the map-like representation of sound frequency in the auditory system. Previous electrophysiology studies from this research and the work of others identified a precise pattern of spontaneous action potential bursts in auditory neurons of the medial nucleus of the trapezoid body (MNTB) that originates in the immature cochlea. Spontaneous action potential bursts are important for short-term synaptic plasticity and refinement of auditory synaptic connections before the onset of hearing. However, the cellular mechanisms of ensemble spontaneous activity in tonotopic maps remain unclear. To address this scientific issue, cellular activity will be measured with calcium indicators, molecules that emit fluorescence in response to changes in intracellular calcium ion concentration. Using state-of-the-art fluorescence two-photon microscopy it will be possible to measure calcium signals in the living brain of anesthetized rodent pups with cellular resolution at different stages of development. The overall hypothesis is that activity-dependent mechanisms, local cellular interactions and experience interact to determine the patterns of ensemble map activity during auditory system development.
The aims are: 1) To define developmental patterns of neuronal ensemble activity in the MNTB; 2) To define developmental patterns of astrocyte differentiation and activity in the MNTB; and 3) To determine the relationship between maternal care, auditory development and MNTB auditory map activity. Altogether, these studies will determine the contribution of glial cells to the maturation of central auditory circuits in mammals, and increase our understanding of how experience and intrinsic programs interact to generate developmental plasticity in the auditory system. Auditory impairments such as deafness are caused by defects in different cellular and molecular components of the ear. However, recent evidence suggests that central nervous system malfunction in the auditory system contributes to neuropsychiatric diseases and other forms of neurologic disease with a developmental onset. The work in this proposal will define how patterns of activity in brain auditory maps change during development, providing clues to understand how these patterns may be affected in disease conditions such as autism and schizophrenia.
Tinnitus, schizophrenia and autism spectrum disorders have in common altered auditory processing and patterns of spontaneous activity. Our experiments will directly determine how parts of the auditory system activate in the absence of sound, and could help explain why some people hear sounds when they shouldn't.
| Shi, Lingyan; Shumyatsky, Pavel; Rodríguez-Contreras, Adrián et al. (2016) Terahertz spectroscopy of brain tissue from a mouse model of Alzheimer's disease. J Biomed Opt 21:15014 |
| Shi, Lingyan; Sordillo, Laura A; Rodríguez-Contreras, Adrián et al. (2016) Transmission in near-infrared optical windows for deep brain imaging. J Biophotonics 9:38-43 |
