Hyperpolarization-Activated Currents and Subthreshold Resonance in Granule Cells of the Olfactory Bulb

eNeuro. 2016 Nov 4;3(5):ENEURO.0197-16.2016. doi: 10.1523/ENEURO.0197-16.2016. eCollection 2016 Sep-Oct.

Abstract

An important contribution to neural circuit oscillatory dynamics is the ongoing activation and inactivation of hyperpolarization-activated currents (Ih). Network synchrony dynamics play an important role in the initial processing of odor signals by the main olfactory bulb (MOB) and accessory olfactory bulb (AOB). In the mouse olfactory bulb, we show that Ih is present in granule cells (GCs), the most prominent inhibitory neuron in the olfactory bulb, and that Ih underlies subthreshold resonance in GCs. In accord with the properties of Ih, the currents exhibited sensitivity to changes in extracellular K+ concentration and ZD7288 (4-ethylphenylamino-1,2-dimethyl-6-methylaminopyrimidin chloride), a blocker of Ih. ZD7288 also caused GCs to hyperpolarize and increase their input resistance, suggesting that Ih is active at rest in GCs. The inclusion of cAMP in the intracellular solution shifted the activation of Ih to less negative potentials in the MOB, but not in the AOB, suggesting that channels with different subunit composition mediate Ih in these regions. Furthermore, we show that mature GCs exhibit Ih-dependent subthreshold resonance in the theta frequency range (4-12 Hz). Another inhibitory subtype in the MOB, the periglomerular cells, exhibited Ih-dependent subthreshold resonance in the delta range (1-4 Hz), while principal neurons, the mitral cells, do not exhibit Ih-dependent subthreshold resonance. Importantly, Ih size, as well as the strength and frequency of resonance in GCs, exhibited a postnatal developmental progression, suggesting that this development of Ih in GCs may differentially contribute to their integration of sensory input and contribution to oscillatory circuit dynamics.

Keywords: HCN; granule cell; neurogenesis; olfactory bulb; resonance.

Publication types

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

MeSH terms

  • Animals
  • Cations, Monovalent / metabolism
  • Cyclic AMP / metabolism
  • Electroporation
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology*
  • Mice, Inbred C57BL
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology
  • Neural Pathways / cytology
  • Neural Pathways / drug effects
  • Neural Pathways / growth & development
  • Neural Pathways / physiology
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / physiology*
  • Neurotransmitter Agents / pharmacology
  • Olfactory Bulb / cytology
  • Olfactory Bulb / drug effects
  • Olfactory Bulb / growth & development*
  • Olfactory Bulb / physiology*
  • Patch-Clamp Techniques
  • Potassium / metabolism
  • Pyrimidines / pharmacology
  • Theta Rhythm
  • Tissue Culture Techniques

Substances

  • Cations, Monovalent
  • Neurotransmitter Agents
  • Pyrimidines
  • ICI D2788
  • Green Fluorescent Proteins
  • Cyclic AMP
  • Potassium