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

Presynaptic structure-function relationships at the vertebrate neuromuscular junction

Homan, Anne (2019) Presynaptic structure-function relationships at the vertebrate neuromuscular junction. Master's Thesis, University of Pittsburgh. (Unpublished)

Download (3MB) | Preview


The impact of presynaptic transmitter release site organization on synaptic function has been a vibrant area of research for synaptic physiologists. Because there is a highly nonlinear relationship between presynaptic calcium influx and subsequent neurotransmitter release at synapses, the organization and density of calcium sources (voltage-gated calcium channels [VGCCs]) relative to calcium sensors located on synaptic vesicles is predicted to play a major role in shaping the dynamics of neurotransmitter release at a synapse. Here we investigate neurotransmitter release at the neuromuscular junction across model preparations in an effort to discern the relationship between VGCC organization and synaptic function. We demonstrate that neurotransmitter release varies considerably across, but not within, individual synapses at the frog and mouse neuromuscular junction (NMJ). Further, we use a computational modeling approach to provide evidence that alterations in the spatiotemporal calcium dynamics within an AZ at the time of release, caused by manipulations in the density and organization of VGCCs, can explain variability in release. In addition, we use our model to demonstrate that VGCC organization is an important determinant of short-term plasticity, and that the differences in AZ arrangement between species can recapitulate the physiological differences between them. We use these studies to provide support for the notion that structure imparts function and argue that a fuller understanding of neurotransmitter release and plasticity must rely on an understanding of the spatio-temporal calcium dynamics at the time of vesicle release.


Social Networking:
Share |


Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Homan, Anneaeh66@pitt.eduaeh66
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee MemberMeriney, Stephenmeriney@pitt.edumeriney
Committee ChairDavis, Brianbmd1@pitt.edubmd1
Committee MemberOswald, Anne-Marieamoswald@pitt.eduamoswald
Date: 26 September 2019
Date Type: Publication
Defense Date: 9 May 2019
Approval Date: 26 September 2019
Submission Date: 14 May 2019
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 122
Institution: University of Pittsburgh
Schools and Programs: Dietrich School of Arts and Sciences > Neuroscience
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: presynaptic; synapses; neuromuscular junction; neurotransmitter release; calcium channels
Date Deposited: 26 Sep 2019 17:51
Last Modified: 26 Sep 2019 17:51


Monthly Views for the past 3 years

Plum Analytics

Actions (login required)

View Item View Item