Excitatory synaptic transmission and network activity are depressed following 1 mechanical injury in cortical neurons

نویسندگان

  • Paulette B. Goforth
  • Jianhua Ren
  • Benjamin S. Schwartz
  • Leslie S. Satin
چکیده

18 In vitro and in vivo traumatic brain injury (TBI) alter the function and expression of glutamate 19 receptors, yet the combined effect of these alterations on cortical excitatory synaptic 20 transmission is unclear. We examined the effect of in vitro mechanical injury on excitatory 21 synaptic function in cultured cortical neurons by assaying synaptically-driven [Ca]i oscillations 22 in small neuronal networks as well as spontaneous and miniature excitatory postsynaptic currents 23 (sEPSCs and mEPSCs). We show that injury decreased the incidence and frequency of 24 spontaneous neuronal [Ca]i oscillations for at least 2 days post-injury. The amplitude of the 25 oscillations was reduced immediately and 2 days post-injury, although a transient rebound at 4 26 hours post-injury was observed due to increased activity of N-methyl-D-aspartate (NMDARs) 27 and calcium permeable α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (CP28 AMPARs). Increased CP-AMPAR function was abolished by the inhibition of protein synthesis. 29 In parallel, mEPSC amplitude decreased immediately, 4 hours and 2 days post-injury, with a 30 transient increase in the contribution of synaptic CP-AMPARs observed at 4 hours post-injury. 31 Decreased mEPSC amplitude was evident after injury, even if NMDARs and CP-AMPARs were 32 blocked pharmacologically, suggesting the decrease reflected alterations in synaptic Glur233 containing, calcium-impermeable AMPARs. Despite the transient increase in CP-AMPAR 34 activity that we observed, the overriding effect of mechanical injury was long-term depression of 35 excitatory neurotransmission that would be expected to contribute to the cognitive deficits of 36 TBI. 37

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Excitatory synaptic transmission and network activity are depressed following mechanical injury in cortical neurons.

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تاریخ انتشار 2011