The hyperpolarization-activated HCN1 channel is important for motor learning and neuronal integration by cerebellar Purkinje cells

Cell. 2003 Nov 26;115(5):551-64. doi: 10.1016/s0092-8674(03)00884-5.


In contrast to our increasingly detailed understanding of how synaptic plasticity provides a cellular substrate for learning and memory, it is less clear how a neuron's voltage-gated ion channels interact with plastic changes in synaptic strength to influence behavior. We find, using generalized and regional knockout mice, that deletion of the HCN1 channel causes profound motor learning and memory deficits in swimming and rotarod tasks. In cerebellar Purkinje cells, which are a key component of the cerebellar circuit for learning of correctly timed movements, HCN1 mediates an inward current that stabilizes the integrative properties of Purkinje cells and ensures that their input-output function is independent of the previous history of their activity. We suggest that this nonsynaptic integrative function of HCN1 is required for accurate decoding of input patterns and thereby enables synaptic plasticity to appropriately influence the performance of motor activity.

Publication types

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

MeSH terms

  • Action Potentials / genetics
  • Afferent Pathways / physiology
  • Animals
  • Cells, Cultured
  • Conditioning, Psychological / physiology
  • Cyclic Nucleotide-Gated Cation Channels
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Ion Channels / deficiency*
  • Ion Channels / genetics
  • Learning / physiology*
  • Maze Learning / physiology
  • Mice
  • Mice, Knockout
  • Motor Skills / physiology
  • Movement / physiology*
  • Nerve Tissue Proteins*
  • Neuronal Plasticity / physiology
  • Potassium Channels
  • Purkinje Cells / cytology
  • Purkinje Cells / metabolism*
  • Synapses / physiology
  • Synaptic Transmission / genetics*


  • Cyclic Nucleotide-Gated Cation Channels
  • Hcn1 protein, mouse
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Ion Channels
  • Nerve Tissue Proteins
  • Potassium Channels