Neuromodulation of I(h) in layer II medial entorhinal cortex stellate cells: a voltage-clamp study

J Neurosci. 2012 Jun 27;32(26):9066-72. doi: 10.1523/JNEUROSCI.0868-12.2012.

Abstract

Stellate cells in layer II of medial entorhinal cortex (mEC) are endowed with a large hyperpolarization-activated cation current [h current (I(h))]. Recent work using in vivo recordings from awake behaving rodents demonstrate that I(h) plays a significant role in regulating the characteristic spatial periodicity of "grid cells" in mEC. A separate, yet related, line of research demonstrates that grid field spacing changes as a function of behavioral context. To understand the neural mechanism or mechanisms that could be underlying these changes in grid spacing, we have conducted voltage-clamp recordings of I(h) in layer II stellate cells. In particular, we have studied I(h) under the influence of several neuromodulators. The results demonstrate that I(h) amplitude can be both upregulated and downregulated through activation of distinct neuromodulators in mEC. Activation of muscarinic acetylcholine receptors produces a significant decrease in the I(h) tail current and a hyperpolarizing shift in the activation, whereas upregulation of cAMP through application of forskolin produces a significant increase in the I(h) amplitude and a depolarizing shift in I(h) activation curve. In addition, there was evidence of differential modulation of I(h) along the dorsal-ventral axis of mEC. Voltage-clamp protocols were also used to determine whether M current is present in stellate cells. In contrast to CA1 pyramidal neurons, which express M current, the data demonstrate that M current is not present in stellate cells. The results from this study provide key insights into a potential mechanism that could be underlying changes seen in grid field spacing during distinct behavioral contexts.

MeSH terms

  • Animals
  • Animals, Newborn
  • Anthracenes / pharmacology
  • Atropine / pharmacology
  • Biophysical Phenomena / drug effects
  • Biophysical Phenomena / physiology
  • Carbachol / pharmacology
  • Cardiotonic Agents / pharmacology
  • Cholinergic Antagonists / pharmacology
  • Colforsin / pharmacology
  • Cyclic AMP / pharmacology
  • Cyclic Nucleotide-Gated Cation Channels / agonists
  • Cyclic Nucleotide-Gated Cation Channels / antagonists & inhibitors
  • Cyclic Nucleotide-Gated Cation Channels / physiology*
  • Electric Stimulation
  • Entorhinal Cortex / cytology*
  • Female
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • In Vitro Techniques
  • Male
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology*
  • Neurons / drug effects
  • Neurons / physiology*
  • Neurotransmitter Agents / pharmacology
  • Patch-Clamp Techniques
  • Potassium Channels / agonists
  • Potassium Channels / physiology*
  • Pyrimidines / pharmacology
  • Rats
  • Rats, Long-Evans
  • Sodium Channel Blockers / pharmacology
  • Tetrodotoxin / pharmacology
  • Time Factors

Substances

  • 10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone
  • Anthracenes
  • Cardiotonic Agents
  • Cholinergic Antagonists
  • Cyclic Nucleotide-Gated Cation Channels
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Neurotransmitter Agents
  • Potassium Channels
  • Pyrimidines
  • Sodium Channel Blockers
  • ICI D2788
  • Colforsin
  • Tetrodotoxin
  • Atropine
  • Carbachol
  • Cyclic AMP