Rapid homeostatic plasticity of intrinsic excitability in a central pattern generator network stabilizes functional neural network output

J Neurosci. 2012 Jul 11;32(28):9649-58. doi: 10.1523/JNEUROSCI.1945-12.2012.

Abstract

Neurons and networks undergo a process of homeostatic plasticity that stabilizes output by integrating activity levels with network and cellular properties to counter longer-term perturbations. Here we describe a rapid compensatory interaction among a pair of potassium currents, I(A) and I(KCa), that stabilizes both intrinsic excitability and network function in the cardiac ganglion of the crab, Cancer borealis. We determined that mRNA levels in single identified neurons for the channels which encode I(A) and I(KCa) are positively correlated, yet the ionic currents themselves are negatively correlated, across a population of motor neurons. We then determined that these currents are functionally coupled; decreasing levels of either current within a neuron causes a rapid increase in the other. This functional interdependence results in homeostatic stabilization of both the individual neuronal and the network output. Furthermore, these compensatory increases are mechanistically independent, suggesting robustness in the maintenance of neural network output that is critical for survival. Together, we generate a complete model for homeostatic plasticity from mRNA to network output where rapid post-translational compensatory mechanisms acting on a reservoir of channels proteins regulated at the level of gene expression provide homeostatic stabilization of both cellular and network activity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 4-Aminopyridine / pharmacology
  • Action Potentials / drug effects
  • Analysis of Variance
  • Animals
  • Brachyura
  • Chelating Agents / pharmacology
  • Cyclosporine / pharmacology
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Electric Stimulation
  • Enzyme Inhibitors / pharmacology
  • Female
  • Ganglia, Invertebrate / cytology
  • Homeostasis* / drug effects
  • Male
  • Motor Neurons / drug effects
  • Motor Neurons / physiology*
  • Nerve Net / physiology*
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology*
  • Patch-Clamp Techniques
  • Potassium Channel Blockers / pharmacology
  • Potassium Channels / genetics
  • Potassium Channels / metabolism
  • RNA, Messenger
  • Sodium Channel Blockers / pharmacology
  • Tetraethylammonium / pharmacology
  • Tetrodotoxin / pharmacology

Substances

  • Chelating Agents
  • Enzyme Inhibitors
  • Potassium Channel Blockers
  • Potassium Channels
  • RNA, Messenger
  • Sodium Channel Blockers
  • 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester
  • Tetrodotoxin
  • Egtazic Acid
  • Tetraethylammonium
  • Cyclosporine
  • 4-Aminopyridine