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

Refinement of inhibitory circuits during development of the mammalian auditory brainstem

Kim, Gunsoo (2004) Refinement of inhibitory circuits during development of the mammalian auditory brainstem. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

Primary Text

Download (2MB) | Preview


Establishing precise neuronal connections is crucial for normal brain function. In many parts of the brain, this is accomplished by refining initially diffuse neuronal connections during development. In contrast to our understanding of the mechanisms by which excitatory connections are refined, the refinement of inhibitory circuits is poorly understood. In this thesis, I investigated the refinement of inhibitory connections in the lateral superior olive (LSO), a mammalian auditory brainstem nucleus involved in sound localization. The glycinergic, and during development also GABAergic, projection from the medial nucleus of the trapezoid body (MNTB) to the LSO is tonotopically organized with a single-cell-level precision in adults. I asked whether and by what mechanisms the precise organization emerges during development.I found that the refinement of this inhibitory pathway is achieved by a large degree of functional elimination of exuberant inputs and strengthening of maintained inputs. Elimination of inputs occurred in a frequency-specific manner, resulting in a sharper inhibitory topography. The topographic refinement occurred while the MNTB inputs act excitatory, raising the possibility that depolarizing action of GABA and glycine is a mechanism underlying the rearrangement of inhibitory synaptic connections. In parallel with the elimination, synaptic responses elicited by the maintained MNTB inputs increased over 10-fold. This was due to a moderate increase in quantal size and a large increase in the number of release sites formed by each MNTB fiber. I further investigated whether olivocochlear efferent neurons that project from the brainstem back to the cochlea play a role in the topographic sharpening. I found that the refinement of the MNTB-LSO pathway is impaired in animals with compromised efferent projections. In both efferent-lesioned rats and mice lacking the ?9 nicotinic acetylcholine receptor subunit, LSO neurons received a greater number of weak MNTB inputs than in control animals. These results indicate that normal olivocochlear efferent projections are necessary for the refinement of the MNTB-LSO pathway. I discuss the possibility that the effect of efferent manipulation could be due to altered levels or temporal patterns of spontaneous activity before hearing onset.


Social Networking:
Share |


Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Kim, Gunsoogukst2@pitt.eduGUKST2
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairSimons, Daniel J
Committee MemberAizenman, Elias
Committee MemberBi, Guo-Qiang
Committee MemberKandler, Karlkkarl@pitt.eduKKARL
Committee MemberTrussell, Laurence O
Committee MemberMeriney, Stephen D
Date: 22 December 2004
Date Type: Completion
Defense Date: 30 November 2004
Approval Date: 22 December 2004
Submission Date: 17 December 2004
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Neurobiology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: plasticity; tonotopic map; uncaging
Other ID:, etd-12172004-051717
Date Deposited: 10 Nov 2011 20:11
Last Modified: 15 Nov 2016 13:54


Monthly Views for the past 3 years

Plum Analytics

Actions (login required)

View Item View Item