Miniature synaptic currents become neurotoxic to chronically silenced neurons

被引：44

作者：

Fishbein, Ianai ^{[1
]}

Segal, Menahem ^{[1
]}

机构：

[1] Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel

来源：

CEREBRAL CORTEX | 2007年 / 17卷 / 06期

关键词：

AMPA receptors; Ca2+ clearance; cortical culture; neurotoxicity; tetrodotoxin;

D O I：

10.1093/cercor/bhl037

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

When deprived of spontaneous ongoing network activity by chronic exposure to tetrodotoxin (TTX), cultured cortical neurons retract their dendrites, lose dendritic spines, and degenerate over a period of 1-2 weeks. Electrophysiological properties of these slowly degenerating neurons prior to their death are normal, but they express very large miniature excitatory postsynaptic currents (mEPSCs). Chronic blockade of these mEPSCs by the alpha-amino-5-hydroxy-3-methyl-4-isoxazole propionic acid (AMPA) receptor antagonist 6,7-Dinitroquinoxaline-2,3-dione (DNQX) had no effect of its own on cell survival, yet, paradoxically, it protected the TTX-silenced neurons from degenerating. TTX-treated neurons also exhibited deficient Ca 21 clearance mechanisms. Thus, upscaled mEPSCs are sufficient to trigger apoptotic processes in otherwise chronically silenced neurons.

引用

页码：1292 / 1306

页数：15

共 47 条

[11] Alterations in dendritic morphology of prefrontal cortical and nucleus accumbens neurons in post-pubertal rats after neonatal excitotoxic lesions of the ventral hippocampus [J].

Flores, G ;

Alquicer, G ;

Silva-Gómez, AB ;

Zaldivar, G ;

Stewart, J ;

Quirion, R ;

Srivastava, LK .

NEUROSCIENCE, 2005, 133 (02) :463-470

[12]

Galvan CD, 2000, J NEUROSCI, V20, P2904

[13] REQUIREMENT FOR BDNF IN ACTIVITY-DEPENDENT SURVIVAL OF CORTICAL-NEURONS [J].

GHOSH, A ;

CARNAHAN, J ;

GREENBERG, ME .

SCIENCE, 1994, 263 (5153) :1618-1623

[14] Functional plasticity triggers formation and pruning of dendritic spines in cultured hippocampal networks [J].

Goldin, M ;

Segal, M ;

Avignone, E .

JOURNAL OF NEUROSCIENCE, 2001, 21 (01) :186-193

[15] Development of neuronal activity and activity-dependent expression of brain-derived neurotrophic factor mRNA in organotypic cultures of rat visual cortex [J].

Gorba, T ;

Klostermann, O ;

Wahle, P .

CEREBRAL CORTEX, 1999, 9 (08) :864-877

[16] Adult-generated hippocampal and neocortical neurons in macaques have a transient existence [J].

Gould, E ;

Vail, N ;

Wagers, M ;

Gross, CG .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (19) :10910-10917

[17] The yin and yang of NMDA receptor signalling [J].

Hardingham, GE ;

Bading, H .

TRENDS IN NEUROSCIENCES, 2003, 26 (02) :81-89

[18] Differential effects of cholinergic lesions on dendritic spines in frontal cortex of young adult and aging rats [J].

Harmon, KM ;

Wellman, CL .

BRAIN RESEARCH, 2003, 992 (01) :60-68

[19] Activity-dependent change in the protein level of brain-derived neurotrophic factor but no change in other neurotrophins in the visual cortex of young and adult ferrets [J].

Ichisaka, S ;

Katoh-Semba, R ;

Hata, Y ;

Ohshima, M ;

Kameyama, K ;

Tsumoto, T .

NEUROSCIENCE, 2003, 117 (02) :361-371

[20] Role of GluR2 expression in AMPA-induced toxicity in cultured murine cerebral cortical neurons [J].

Jensen, JB ;

Lund, TM ;

Timmermann, DB ;

Schousboe, A ;

Pickering, DS .

JOURNAL OF NEUROSCIENCE RESEARCH, 2001, 65 (03) :267-277

← 1 2 3 4 5 →