Using inhibitory precursor cell transplantation to investigate the role of inhibition in noise-induced pathology of the inferior colliculusOwoc, Maryanna Stephanie (2022) Using inhibitory precursor cell transplantation to investigate the role of inhibition in noise-induced pathology of the inferior colliculus. Doctoral Dissertation, University of Pittsburgh. (Unpublished)
AbstractThe inferior colliculus (IC) is a nexus of auditory processing in the midbrain, in that it receives and integrates ascending, descending, commissural, and multimodal inputs. As such, the IC has been implicated in refining the response to auditory stimulation and multimodal integration. The IC consists of a central nucleus (CNIC) and surrounding cortex (CtxIC) – ascending inputs primarily innervate the CNIC, whereas descending and multimodal inputs target the CtxIC. The distinct nature of inputs to CNIC and CtxIC neurons predicts distinct response properties in these IC subdivisions. However, distinguishing neurons from the CNIC and CtxIC based on response properties alone has remained challenging. In chapter 2, using in-vivo electrophysiological recordings in anesthetized mice, we show that CNIC and CtxIC neurons exhibit small but significant differences in receptive field parameters. When combined using machine-learning models, we show that neural recordings can be localized to the CNIC or CtxIC solely based on response properties. The methods developed here would also allow us to better target interventions to functionally-defined IC regions and to characterize response properties in future experiments that employ the circuit manipulations outlined below. Neural response properties in the IC arise from the convergence of excitatory and inhibitory inputs. Noise exposure can lead to decreased inhibition in the IC and has been implicated in the development of central auditory pathologies. In chapters 3 and 4 we investigate whether transplantation of inhibitory precursor cells derived from the medial ganglionic eminence (MGE) can mitigate the effects of noise exposure. We found that transplanted MGE cells survive, migrate, and differentiate into primarily inhibitory neurons in the IC (chapter 3). Critically, we found that transplantation of MGE cells into the IC of noise-exposed mice mitigated the noise induced shifts in auditory function as measured by the acoustic startle response (chapter 4). Our data provide the first evidence that local increases in inhibition may be useful in mitigating a behavioral effect of noise exposure. Future research using these techniques could provide insight into the mechanisms underlying the development of noise induced pathology and the response properties that contribute to auditory processing in the normal and pathologic states. Share
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