Modulation of thalamocortical oscillations by TRIP8b, an auxiliary subunit for HCN channels

Brain Struct Funct. 2018 Apr;223(3):1537-1564. doi: 10.1007/s00429-017-1559-z. Epub 2017 Nov 22.


Hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels have important functions in controlling neuronal excitability and generating rhythmic oscillatory activity. The role of tetratricopeptide repeat-containing Rab8b-interacting protein (TRIP8b) in regulation of hyperpolarization-activated inward current, I h, in the thalamocortical system and its functional relevance for the physiological thalamocortical oscillations were investigated. A significant decrease in I h current density, in both thalamocortical relay (TC) and cortical pyramidal neurons was found in TRIP8b-deficient mice (TRIP8b-/-). In addition basal cAMP levels in the brain were found to be decreased while the availability of the fast transient A-type K+ current, I A, in TC neurons was increased. These changes were associated with alterations in intrinsic properties and firing patterns of TC neurons, as well as intrathalamic and thalamocortical network oscillations, revealing a significant increase in slow oscillations in the delta frequency range (0.5-4 Hz) during episodes of active-wakefulness. In addition, absence of TRIP8b suppresses the normal desynchronization response of the EEG during the switch from slow-wave sleep to wakefulness. It is concluded that TRIP8b is necessary for the modulation of physiological thalamocortical oscillations due to its direct effect on HCN channel expression in thalamus and cortex and that mechanisms related to reduced cAMP signaling may contribute to the present findings.

Keywords: Delta oscillations; HCN channels; I A; In vivo; Knockout mice; TRIP8b; Thalamocortical oscillations.

MeSH terms

  • Action Potentials / genetics
  • Adenine / analogs & derivatives
  • Adenine / pharmacology
  • Adenylyl Cyclase Inhibitors / pharmacology
  • Animals
  • Cardiovascular Agents / pharmacology
  • Cerebral Cortex / cytology
  • Cerebral Cortex / physiology*
  • Cyclic AMP / pharmacology
  • Cyclic GMP / analogs & derivatives
  • Cyclic GMP / pharmacology
  • Female
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / physiology
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Models, Neurological
  • Neural Pathways / physiology*
  • Peroxins / genetics
  • Peroxins / metabolism*
  • Pyrimidines / pharmacology
  • Sodium Channel Blockers / pharmacology
  • Tetrodotoxin / pharmacology
  • Thalamus / physiology*
  • Thionucleotides / pharmacology


  • Adenylyl Cyclase Inhibitors
  • Cardiovascular Agents
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Membrane Proteins
  • Peroxins
  • Pex5l protein, mouse
  • Pyrimidines
  • Sodium Channel Blockers
  • Thionucleotides
  • ICI D2788
  • 8-bromoguanosino-3',5'-cyclic monophosphorothioate
  • 9-(tetrahydro-2-furyl)-adenine
  • Tetrodotoxin
  • Cyclic AMP
  • Cyclic GMP
  • Adenine