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Role of GABA Co-release in Glycinergic Synapses and Target-specific Refinement of Inhibitory Axon Collaterals in the Superior Olivary Complex

Lee, Jongwon (2023) Role of GABA Co-release in Glycinergic Synapses and Target-specific Refinement of Inhibitory Axon Collaterals in the Superior Olivary Complex. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Dale’s principle, the idea of ‘one neuron, one neurotransmitter’, has been challenged in the past two decades. It is now understood that a single neuron, synapse, or vesicle can release multiple neurotransmitters. Dual inhibitory neurotransmission of GABA (gamma-aminobutyric acid) and glycine is present in many neuronal populations, including the developing medial nucleus of the trapezoid body (MNTB) in the auditory brainstem. The developing MNTB is primarily glycinergic but transiently also GABAergic during pre-hearing development when the substantial refinement of the connections and synaptic maturation takes place, which suggests that GABA co-release plays a developmental role in glycinergic neurons. In this thesis, I address the functions of GABA co-release in the developmental refinement of glycinergic MNTB projections in the mouse superior olivary complex.
In Chapter 1, I provide a brief review of the multiple neurotransmitter release, postnatal refinement of neuronal connections, and circuit organization of the superior olivary complex. In Chapter 2, I demonstrate that GABA co-release does not contribute to the developmental refinement of fiber elimination or strengthening of MNTB connections to principal neurons in the lateral superior olive (LSO), but instead regulates the development of functional synaptic architectures of MNTB-LSO connections. This abnormality appears to be associated with the reliability of synaptic transmission when presynaptic neurons are highly active. I propose that GABA co-release promotes the development of MNTB-LSO synapses with a large number of release sites and vesicle pools, thereby supporting reliable synaptic transmission in high presynaptic activity for auditory processing. In Chapter 3, I demonstrate that MNTB axon collaterals innervating LSO principal, lateral superior olive (LOC), and superior paraolivary nucleus (SPON) neurons undergo distinct patterns of elimination and strengthening during development, namely, the target-specific refinement. I show that the target-specific refinement occurs independent of the presence of GABA co-release. In Chapter 4, I discuss the developmental functions of GABA co-release in glycinergic synapses and the hypotheses regarding the mechanisms underlying the target-specific refinement of diverging inhibitory axon collaterals.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Lee, Jongwonjol72@pitt.edujol720000-0003-0220-7470
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairSadagopan, Srivatsunvatsun@pitt.eduvatsun
Thesis AdvisorKandler, Karlkkarl@pitt.edukkarl
Committee MemberJacob, Tijatcj11@pitt.edutcj11
Committee MemberMeriney, Stephenmeriney@pitt.edumeriney
Committee MemberRoss, Sarahsaross@pitt.edusaross
Committee MemberXu-Friedman,
Date: 4 October 2023
Date Type: Publication
Defense Date: 16 March 2023
Approval Date: 4 October 2023
Submission Date: 8 May 2023
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 185
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Neurobiology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: GABA; glycine; GABA co-release; co-release; co-transmission; development; circuit refinement; synaptic transmission; auditory system; SOC; MNTB; LSO; SPON; LOC;
Date Deposited: 04 Oct 2023 16:33
Last Modified: 04 Oct 2023 16:33


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