A microfluidic based in vitro model of synaptic competition

被引:28
作者
Coquinco, Ainsley [1 ]
Kojic, Luba [1 ]
Wen, Wendy [1 ]
Wang, Yu Tian [1 ]
Jeon, Noo Li [2 ]
Milnerwood, Austen J. [1 ,3 ,4 ]
Cynader, Max [1 ]
机构
[1] Univ British Columbia, Brain Res Ctr, Vancouver, BC V6T 2B5, Canada
[2] Seoul Natl Univ, Sch Mech & Aerosp Engn, Div World Class Univ Multiscale Mech Design, Seoul 151744, South Korea
[3] Univ British Columbia, Dept Med, Div Neurol, Vancouver, BC V6T 2B5, Canada
[4] Univ British Columbia, Ctr Appl Neurogenet, Vancouver, BC V6T 2B5, Canada
基金
加拿大健康研究院; 加拿大自然科学与工程研究理事会;
关键词
Synaptic plasticity; Microfluidics; Competition; AMPA RECEPTORS; PLASTICITY; SUBUNIT; PERIOD; RESPONSES; DYNAMICS; CORTEX; GLUR2; LTP;
D O I
10.1016/j.mcn.2014.03.001
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Synaptic competition is widely believed to be central to the formation and function of neuronal networks, yet the underlying mechanisms are poorly described. To investigate synaptic competition in vitro, we have developed a novel two input pathway competition model using a 3-compartment microfluidic device. Axons from cultured rat cortical neurons from two different lateral compartments (inputs) innervate a common neuronal population in a separate central compartment. Inhibiting one input's activity, using the GABA(A)R agonist muscimol, resulted in increased synapse numbers and axon elongation of the opposing untreated (uninhibited) inputs in the central compartment. Time lapse imaging revealed that uninhibited inputs outgrew and outconnected their inhibited counterparts. This form of competition occurs during a sensitive period ending prior to 21 DIV and is NMDAR and CamKII dependent. Surprisingly, this form of plasticity was dependent on the age of the center compartment neurons but not of the competing inputs. (C) 2014 Elsevier Inc. All rights reserved.
引用
收藏
页码:43 / 52
页数:10
相关论文
共 36 条
[1]   NMDA receptors inhibit synapse unsilencing during brain development [J].
Adesnik, Hillel ;
Li, Guangnan ;
During, Matthew J. ;
Pleasure, Samuel J. ;
Nicoll, Roger A. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (14) :5597-5602
[2]   Tyrosine phosphorylation of GluR2 is required for insulin-stimulated AMPA receptor endocytosis and LTD [J].
Ahmadian, G ;
Ju, W ;
Liu, LD ;
Wyszynski, M ;
Lee, SH ;
Dunah, AW ;
Taghibiglou, C ;
Wang, YS ;
Lu, J ;
Wong, TP ;
Sheng, M ;
Wang, YT .
EMBO JOURNAL, 2004, 23 (05) :1040-1050
[3]   Synapse elimination accompanies functional plasticity in hippocampal neurons [J].
Bastrikova, Natalia ;
Gardner, Gregory A. ;
Reece, Jeff M. ;
Jeromin, Andreas ;
Dudek, Serena M. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (08) :3123-3127
[4]   Interaction with the NMDA receptor locks CaMKII in an active conformation [J].
Bayer, KU ;
De Koninck, P ;
Leonard, AS ;
Hell, JW ;
Schulman, H .
NATURE, 2001, 411 (6839) :801-805
[5]   Multiple forms of synaptic plasticity triggered by selective suppression of activity in individual neurons [J].
Burrone, J ;
O'Byrne, M ;
Murthy, VN .
NATURE, 2002, 420 (6914) :414-418
[6]   THE DISTRIBUTION OF GLUTAMATE RECEPTORS IN CULTURED RAT HIPPOCAMPAL-NEURONS - POSTSYNAPTIC CLUSTERING OF AMPA-SELECTIVE SUBUNITS [J].
CRAIG, AM ;
BLACKSTONE, CD ;
HUGANIR, RL ;
BANKER, G .
NEURON, 1993, 10 (06) :1055-1068
[7]  
Cull-Candy Stuart G, 2004, Sci STKE, V2004, pre16, DOI 10.1126/stke.2552004re16
[8]   Nucleofection of primary neurons [J].
Gärtner, A ;
Collin, L ;
Lalli, G .
METHODS IN ENZYMOLOGY, VOL 406, REGULATORS AND EFFECTORS OF SMALL GTPASES: RHO FAMILY, 2006, 406 :374-388
[9]   Single-Cell Optogenetic Excitation Drives Homeostatic Synaptic Depression [J].
Goold, Carleton P. ;
Nicoll, Roger A. .
NEURON, 2010, 68 (03) :512-528
[10]  
Gordon JA, 1996, J NEUROSCI, V16, P3274