Activity-dependent excitability changes in hippocampal CA3 cell Schaffer axons

J Physiol. 2004 Oct 15;560(Pt 2):491-503. doi: 10.1113/jphysiol.2004.071225. Epub 2004 Aug 19.


The membrane potential changes following action potentials in thin unmyelinated cortical axons with en passant boutons may be important for synaptic release and conduction abilities of such axons. In the lack of intra-axonal recording techniques we have used extracellular excitability testing as an indirect measure of the after-potentials. We recorded from individual CA3 soma in hippocampal slices and activated the axon with a range of stimulus intensities. When conditioning and test stimuli were given to the same site the excitability changes were partly masked by local effects of the stimulating electrode at intervals < 5 ms. Therefore, we elicited the conditioning action potential from one axonal branch and tested the excitability of another branch. We found that a single action potential reduced the axonal excitability for 15 ms followed by an increased excitability for approximately 200 ms at 24 degrees C. Using field recordings of axonal action potentials we show that raising the temperature to 34 degrees C reduced the magnitude and duration of the initial depression. However, the duration of the increased excitability was very similar (time constant 135 +/- 20 ms) at 24 and 34 degrees C, and with 2.0 and 0.5 mM Ca2+ in the bath. At stimulus rates > 1 Hz, a condition that activates a hyperpolarization-activated current (Ih) in these axons, the decay was faster than at lower stimulation rates. This effect was reduced by the Ih blocker ZD7288. These data suggest that the decay time course of the action potential-induced hyperexcitability is determined by the membrane time constant.

MeSH terms

  • Action Potentials / physiology
  • Animals
  • Axons / physiology*
  • Calcium / metabolism
  • Electric Stimulation
  • Electrophysiology
  • Extracellular Fluid / metabolism
  • Female
  • Hippocampus / cytology
  • Hippocampus / physiology*
  • In Vitro Techniques
  • Male
  • Neurons / physiology*
  • Osmolar Concentration
  • Presynaptic Terminals / physiology
  • Rats
  • Rats, Wistar
  • Refractory Period, Electrophysiological
  • Synapses / physiology
  • Time Factors


  • Calcium