Activity-dependent synaptic plasticity is crucial for the development and function of the nervous system. From my previous studies, we have found that in simple networks of cultured neurons, (i) correlated pre- and postsynaptic spiking activity induces different types of synaptic modification depending on precise spike timing; and (ii) synaptic strengthening induced at one synapse appears to propagate to specific neighboring sites in a network. Such temporal and spatial specificity of spike timing-dependent plasticity (STDP) reflects intriguing cellular mechanisms and bears important consequences for the development and function of neuronal circuits. Here, we propose a series of experiments aimed at establishing a set of spatio-temporal rules for STDP and its propagation, and revealing the underlying cellular signaling mechanisms.
In Aim 1, we will identify quantitative rules for the temporal integration of STDP, emphasizing the involvement of short-term plasticity and the interaction between potentiation and depression processes.
In Aim 2, we will use a novel local activation method to characterize STDP at single or a small number of identified synaptic boutons and to characterize the directions, ranges and speeds of the propagation of STDP to other identified boutons.
In Aim 3, we will combine imaging and electrophysiological techniques to investigate Ca 2+ dynamics in the induction and propagation of STDP, and to evaluate the contributions from different Ca 2+ sources. The proposed project, by pursuing a set of quantitative rules for synaptic modification and a mechanistic understanding of these rules, promises to bridge the gap between synaptic physiology and neural network behavior, and advance our understanding of how experience shapes the development and function of neuronal circuits in the brain. Ultimately, these studies will provide insights into and may lead to cures for human diseases in the nervous system, especially those related to learning and memory.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH066962-05
Application #
7228203
Study Section
Integrative, Functional and Cognitive Neuroscience 8 (IFCN)
Program Officer
Asanuma, Chiiko
Project Start
2003-07-01
Project End
2008-04-30
Budget Start
2007-05-01
Budget End
2008-04-30
Support Year
5
Fiscal Year
2007
Total Cost
$247,172
Indirect Cost
Name
University of Pittsburgh
Department
Biology
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Gerkin, Richard C; Nauen, David W; Xu, Fang et al. (2013) Homeostatic regulation of spontaneous and evoked synaptic transmission in two steps. Mol Brain 6:38
Nauen, David W; Bi, Guo-Qiang (2012) Measuring action potential-evoked transmission at individual synaptic contacts. J Neural Eng 9:036014
Zhang, Ji-Chuan; Lau, Pak-Ming; Bi, Guo-Qiang (2009) Gain in sensitivity and loss in temporal contrast of STDP by dopaminergic modulation at hippocampal synapses. Proc Natl Acad Sci U S A 106:13028-33
Madi, Asaf; Friedman, Yonatan; Roth, Dalit et al. (2008) Genome holography: deciphering function-form motifs from gene expression data. PLoS One 3:e2708
Gerkin, Richard C; Lau, Pak-Ming; Nauen, David W et al. (2007) Modular competition driven by NMDA receptor subtypes in spike-timing-dependent plasticity. J Neurophysiol 97:2851-62
Volman, Vladislav; Gerkin, Richard C; Lau, Pak-Ming et al. (2007) Calcium and synaptic dynamics underlying reverberatory activity in neuronal networks. Phys Biol 4:91-103
Shtrahman, Matthew; Yeung, Chuck; Nauen, David W et al. (2005) Probing vesicle dynamics in single hippocampal synapses. Biophys J 89:3615-27
Bi, Guo-Qiang; Rubin, Jonathan (2005) Timing in synaptic plasticity: from detection to integration. Trends Neurosci 28:222-8
Wang, Huai-Xing; Gerkin, Richard C; Nauen, David W et al. (2005) Coactivation and timing-dependent integration of synaptic potentiation and depression. Nat Neurosci 8:187-93
Lau, Pak-Ming; Bi, Guo-Qiang (2005) Synaptic mechanisms of persistent reverberatory activity in neuronal networks. Proc Natl Acad Sci U S A 102:10333-8

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