Mechanism of graded persistent cellular activity of entorhinal cortex layer v neurons

Neuron. 2006 Mar 2;49(5):735-46. doi: 10.1016/j.neuron.2006.01.036.

Abstract

Working memory is an emergent property of neuronal networks, but its cellular basis remains elusive. Recent data show that principal neurons of the entorhinal cortex display persistent firing at graded firing rates that can be shifted up or down in response to brief excitatory or inhibitory stimuli. Here, we present a model of a potential mechanism for graded firing. Our multicompartmental model provides stable plateau firing generated by a nonspecific calcium-sensitive cationic (CAN) current. Sustained firing is insensitive to small variations in Ca2+ concentration in a neutral zone. However, both high and low Ca2+ levels alter firing rates. Specifically, increases in persistent firing rate are triggered only during high levels of calcium, while decreases in rate occur in the presence of low levels of calcium. The model is consistent with detailed experimental observations and provides a mechanism for maintenance of memory-related activity in individual neurons.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology*
  • Animals
  • Calcium / metabolism
  • Calcium Channels / physiology
  • Calcium Signaling / drug effects
  • Calcium Signaling / physiology
  • Dose-Response Relationship, Radiation
  • Electric Stimulation / methods
  • Entorhinal Cortex / cytology*
  • Enzyme Inhibitors / pharmacology
  • In Vitro Techniques
  • Indoles / pharmacology
  • Models, Neurological*
  • Neurons / drug effects
  • Neurons / physiology*
  • Nonlinear Dynamics
  • Potassium Channels / physiology
  • Rats
  • Thapsigargin / pharmacology
  • Time Factors

Substances

  • Calcium Channels
  • Enzyme Inhibitors
  • Indoles
  • Potassium Channels
  • Thapsigargin
  • Calcium
  • cyclopiazonic acid