Quantitative assessment of the distributions of membrane conductances involved in action potential backpropagation along basal dendrites

J Neurophysiol. 2009 Mar;101(3):1524-41. doi: 10.1152/jn.00651.2007. Epub 2008 Dec 31.

Abstract

Basal dendrites of prefrontal cortical neurons receive strong synaptic drive from recurrent excitatory synaptic inputs. Synaptic integration within basal dendrites is therefore likely to play an important role in cortical information processing. Both synaptic integration and synaptic plasticity depend crucially on dendritic membrane excitability and the backpropagation of action potentials. We carried out multisite voltage-sensitive dye imaging of membrane potential transients from thin basal branches of prefrontal cortical pyramidal neurons before and after application of channel blockers. We found that backpropagating action potentials (bAPs) are predominantly controlled by voltage-gated sodium and A-type potassium channels. In contrast, pharmacologically blocking the delayed rectifier potassium, voltage-gated calcium, or I(h) conductance had little effect on dendritic AP propagation. Optically recorded bAP waveforms were quantified and multicompartmental modeling was used to link the observed behavior with the underlying biophysical properties. The best-fit model included a nonuniform sodium channel distribution with decreasing conductance with distance from the soma, together with a nonuniform (increasing) A-type potassium conductance. AP amplitudes decline with distance in this model, but to a lesser extent than previously thought. We used this model to explore the mechanisms underlying two sets of published data involving high-frequency trains of APs and the local generation of sodium spikelets. We also explored the conditions under which I(A) down-regulation would produce branch strength potentiation in the proposed model. Finally, we discuss the hypothesis that a fraction of basal branches may have different membrane properties compared with sister branches in the same dendritic tree.

Publication types

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

MeSH terms

  • 4-Aminopyridine / pharmacology
  • Action Potentials / drug effects
  • Action Potentials / physiology*
  • Animals
  • Animals, Newborn
  • Biophysical Phenomena / physiology*
  • Calcium / metabolism
  • Dendrites / drug effects
  • Dendrites / physiology*
  • Electric Conductivity
  • Electric Stimulation / methods
  • In Vitro Techniques
  • Ion Channel Gating / physiology
  • Models, Neurological
  • Neurons / cytology*
  • Patch-Clamp Techniques
  • Potassium Channel Blockers / pharmacology
  • Prefrontal Cortex / cytology
  • Rats
  • Rats, Sprague-Dawley
  • Signal Processing, Computer-Assisted
  • Sodium Channel Blockers / pharmacology
  • Styrenes / metabolism
  • Tetrodotoxin / pharmacology

Substances

  • JPW 3028
  • Potassium Channel Blockers
  • Sodium Channel Blockers
  • Styrenes
  • Tetrodotoxin
  • 4-Aminopyridine
  • Calcium