Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form

Using inhibitory precursor cell transplantation to investigate the role of inhibition in noise-induced pathology of the inferior colliculus

Owoc, 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 (Unpublished)

Download (4MB) | Preview


The 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.


Social Networking:
Share |


Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Owoc, Maryanna Stephaniemso12@pitt.edumso120000000237551071
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairSadagopan,
Thesis AdvisorKandler,
Committee MemberKuhlman,
Committee MemberSeal, Rebeccarpseal@pitt.ed
Committee MemberRoss,
Committee MemberBrandacher,
Date: 7 May 2022
Date Type: Publication
Defense Date: 28 February 2022
Approval Date: 7 May 2022
Submission Date: 4 March 2022
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 204
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Neurobiology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: noise exposure, inferior colliculus, medial ganglionic eminence, electrophysiology
Date Deposited: 07 May 2022 21:44
Last Modified: 07 May 2022 21:44


Monthly Views for the past 3 years

Plum Analytics

Actions (login required)

View Item View Item