Electrophysiological Abnormalities in Both Axotomized and Nonaxotomized Pyramidal Neurons Following Mild Traumatic Brain Injury

J Neurosci. 2012 May 9;32(19):6682-7. doi: 10.1523/JNEUROSCI.0881-12.2012.

Abstract

Mild traumatic brain injury (mTBI) often produces lasting detrimental effects on cognitive processes. The mechanisms underlying neurological abnormalities have not been fully identified, in part due to the diffuse pathology underlying mTBI. Here we employ a mouse model of mTBI that allows for identification of both axotomized and intact neurons in the living cortical slice via neuronal expression of yellow fluorescent protein. Both axotomized and intact neurons recorded within injured cortex are healthy with a normal resting membrane potential, time constant (τ), and input resistance (R(in)). In control cortex, 25% of cells show an intrinsically bursting action potential (AP) firing pattern, and the rest respond to injected depolarizing current with a regular-spiking pattern. At 2 d postinjury, intrinsic bursting activity is lost within the intact population. The AP amplitude is increased and afterhyperpolarization duration decreased in axotomized neurons at 1 and 2 d postinjury. In contrast, intact neurons also show these changes at 1 d, but recover by 2 d postinjury. Two measures suggest an initial decrease in excitability in axotomized neurons followed by an increase in excitability within intact neurons. The rheobase is significantly increased in axotomized neurons at 1 d postinjury. The slope of the plot of AP frequency versus injected current is larger for intact neurons at 2 d postinjury. Together, these results demonstrate that intact and axotomized neurons are both affected by mTBI, resulting in different changes in neuronal excitability that may contribute to network dysfunction following TBI.

Publication types

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

MeSH terms

  • Action Potentials / physiology*
  • Animals
  • Axotomy / methods
  • Brain Injuries / pathology*
  • Brain Injuries / physiopathology
  • Electrophysiological Phenomena / physiology*
  • Male
  • Mice
  • Neurons / pathology
  • Neurons / physiology
  • Pyramidal Cells / injuries*
  • Pyramidal Cells / pathology*