Neurons communicate with each other through synaptic transmission. Changes in the effectiveness of synapses underlie the ability of neuronal networks to store and retrieve information, the cellular representation of learning and memory. One form of synaptic plasticity is facilitation, a phenomenon by which synapses becomes transiently more effective following repeated use. Facilitation is a ubiquitous phenomenon observed at many synapses and represents a very general process controlling the effectiveness of synapses. This application addresses the question of what mechanisms operate within the synaptic terminal to allow secretion to increase with increased rates of use. The fundamental event in synaptic transmission is the entry of calcium into the synaptic terminal during an action potential, leading to the fusion of a synaptic vesicle with the terminal membrane. The classical interpretation of facilitation was repetitive nerve stimulation increases the Ca++ concentration at presynaptic release sites, which in turn increases the probability of each vesicle to be released. Recently it was demonstrated that the number of synaptic vesicles properly activated to be released (the releasable pool of quanta) is highly dynamic and has a critical role in synaptic plasticity. The goal of the proposed work is to develop and test a quantitative model of neurosecretion, which will clarify the role of the increase in residual calcium, activation of release sites and the increase in the releasable pool of quanta and thereby account for presynaptic facilitation. Facilitation has strictly distinguishable components: short-term facilitation (STF) and long-term facilitation (LTF), which results from different underlying mechanisms. The proposed work will take advantage of the separation of these two components to distinguish between different mechanisms. Experiments will test the hypothesis that STF is determined by an increase of intracellular calcium and vesicle mobilization, while LTF is additionally controlled by activation of previously silent release sites. The approach is to combine computer simulations of presynaptic processes with electrophysiological detection of the number of released vesticles.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH061059-05
Application #
6796156
Study Section
Special Emphasis Panel (ZRG1-IFCN-8 (01))
Program Officer
Glanzman, Dennis L
Project Start
2000-09-02
Project End
2006-03-31
Budget Start
2004-09-01
Budget End
2006-03-31
Support Year
5
Fiscal Year
2004
Total Cost
$197,888
Indirect Cost
Name
Lehigh University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
808264444
City
Bethlehem
State
PA
Country
United States
Zip Code
18015
Sabeva, Nadezhda S; Bykhovskaia, Maria (2017) FM1-43 Photoconversion and Electron Microscopy Analysis at the Drosophila Neuromuscular Junction. Bio Protoc 7:
Long, Rong; Hui, Chung-Yuen; Jagota, Anand et al. (2012) Adhesion energy can regulate vesicle fusion and stabilize partially fused states. J R Soc Interface 9:1555-67
Bykhovskaia, Maria (2011) Synapsin regulation of vesicle organization and functional pools. Semin Cell Dev Biol 22:387-92
Akbergenova, Y; Bykhovskaia, M (2010) Synapsin regulates vesicle organization and activity-dependent recycling at Drosophila motor boutons. Neuroscience 170:441-52
Coleman, William L; Bykhovskaia, Maria (2010) Cooperative regulation of neurotransmitter release by Rab3a and synapsin II. Mol Cell Neurosci 44:190-200
Akbergenova, Yulia; Bykhovskaia, Maria (2009) Enhancement of the endosomal endocytic pathway increases quantal size. Mol Cell Neurosci 40:199-206
Coleman, William L; Bykhovskaia, Maria (2009) Rab3a-mediated vesicle recruitment regulates short-term plasticity at the mouse diaphragm synapse. Mol Cell Neurosci 41:286-96
Akbergenova, Yulia; Bykhovskaia, Maria (2009) Stimulation-induced formation of the reserve pool of vesicles in Drosophila motor boutons. J Neurophysiol 101:2423-33
Coleman, William L; Bykhovskaia, Maria (2009) Synapsin I accelerates the kinetics of neurotransmitter release in mouse motor terminals. Synapse 63:531-3
Coleman, William L; Bill, Cynthia A; Simsek-Duran, Fatma et al. (2008) Synapsin II and calcium regulate vesicle docking and the cross-talk between vesicle pools at the mouse motor terminals. J Physiol 586:4649-73

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