A calcium-dependent plasticity rule for HCN channels maintains activity homeostasis and stable synaptic learning

PLoS One. 2013;8(2):e55590. doi: 10.1371/journal.pone.0055590. Epub 2013 Feb 4.

Abstract

Theoretical and computational frameworks for synaptic plasticity and learning have a long and cherished history, with few parallels within the well-established literature for plasticity of voltage-gated ion channels. In this study, we derive rules for plasticity in the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, and assess the synergy between synaptic and HCN channel plasticity in establishing stability during synaptic learning. To do this, we employ a conductance-based model for the hippocampal pyramidal neuron, and incorporate synaptic plasticity through the well-established Bienenstock-Cooper-Munro (BCM)-like rule for synaptic plasticity, wherein the direction and strength of the plasticity is dependent on the concentration of calcium influx. Under this framework, we derive a rule for HCN channel plasticity to establish homeostasis in synaptically-driven firing rate, and incorporate such plasticity into our model. In demonstrating that this rule for HCN channel plasticity helps maintain firing rate homeostasis after bidirectional synaptic plasticity, we observe a linear relationship between synaptic plasticity and HCN channel plasticity for maintaining firing rate homeostasis. Motivated by this linear relationship, we derive a calcium-dependent rule for HCN-channel plasticity, and demonstrate that firing rate homeostasis is maintained in the face of synaptic plasticity when moderate and high levels of cytosolic calcium influx induced depression and potentiation of the HCN-channel conductance, respectively. Additionally, we show that such synergy between synaptic and HCN-channel plasticity enhances the stability of synaptic learning through metaplasticity in the BCM-like synaptic plasticity profile. Finally, we demonstrate that the synergistic interaction between synaptic and HCN-channel plasticity preserves robustness of information transfer across the neuron under a rate-coding schema. Our results establish specific physiological roles for experimentally observed plasticity in HCN channels accompanying synaptic plasticity in hippocampal neurons, and uncover potential links between HCN-channel plasticity and calcium influx, dynamic gain control and stable synaptic learning.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium / metabolism*
  • Computer Simulation
  • Cyclic Nucleotide-Gated Cation Channels / physiology*
  • Homeostasis
  • Humans
  • Learning / physiology*
  • Models, Neurological*
  • Neuronal Plasticity / physiology*
  • Pyramidal Cells / cytology
  • Pyramidal Cells / physiology*
  • Receptors, N-Methyl-D-Aspartate / physiology
  • Synapses / physiology
  • Synaptic Transmission / physiology*

Substances

  • Cyclic Nucleotide-Gated Cation Channels
  • Receptors, N-Methyl-D-Aspartate
  • Calcium

Grant support

This work was supported by a career development award to RN by the International Human Frontier Science Program Organization. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.