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

J Neurophysiol. 2011 May;105(5):2350-63. doi: 10.1152/jn.00467.2010. Epub 2011 Feb 23.


In vitro and in vivo traumatic brain injury (TBI) alter the function and expression of glutamate receptors, yet the combined effect of these alterations on cortical excitatory synaptic transmission is unclear. We examined the effect of in vitro mechanical injury on excitatory synaptic function in cultured cortical neurons by assaying synaptically driven intracellular free calcium ([Ca(2+)](i)) oscillations in small neuronal networks as well as spontaneous and miniature excitatory postsynaptic currents (mEPSCs). We show that injury decreased the incidence and frequency of spontaneous neuronal [Ca(2+)](i) oscillations for at least 2 days post-injury. The amplitude of the oscillations was reduced immediately and 2 days post-injury, although a transient rebound at 4 h post-injury was observed due to increased activity of N-methyl-d-aspartate (NMDARs) and calcium-permeable α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (CP-AMPARs). Increased CP-AMPAR function was abolished by the inhibition of protein synthesis. In parallel, mEPSC amplitude decreased immediately, 4 h, and 2 days post-injury, with a transient increase in the contribution of synaptic CP-AMPARs observed at 4 h post-injury. Decreased mEPSC amplitude was evident after injury, even if NMDARs and CP-AMPARs were blocked pharmacologically, suggesting the decrease reflected alterations in synaptic Glur2-containing, calcium-impermeable AMPARs. Despite the transient increase in CP-AMPAR activity that we observed, the overriding effect of mechanical injury was long-term depression of excitatory neurotransmission that would be expected to contribute to the cognitive deficits of TBI.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Animals, Newborn
  • Calcium Signaling / physiology
  • Cells, Cultured
  • Excitatory Postsynaptic Potentials / physiology*
  • Long-Term Synaptic Depression / physiology*
  • Neocortex / cytology
  • Neocortex / physiology*
  • Nerve Net / cytology
  • Nerve Net / injuries*
  • Nerve Net / physiology*
  • Neuronal Plasticity / physiology
  • Neurons / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Synaptic Transmission / physiology