Corticospinal-specific HCN expression in mouse motor cortex: I(h)-dependent synaptic integration as a candidate microcircuit mechanism involved in motor control

J Neurophysiol. 2011 Nov;106(5):2216-31. doi: 10.1152/jn.00232.2011. Epub 2011 Jul 27.


Motor cortex is a key brain center involved in motor control in rodents and other mammals, but specific intracortical mechanisms at the microcircuit level are largely unknown. Neuronal expression of hyperpolarization-activated current (I(h)) is cell class specific throughout the nervous system, but in neocortex, where pyramidal neurons are classified in various ways, a systematic pattern of expression has not been identified. We tested whether I(h) is differentially expressed among projection classes of pyramidal neurons in mouse motor cortex. I(h) expression was high in corticospinal neurons and low in corticostriatal and corticocortical neurons, a pattern mirrored by mRNA levels for HCN1 and Trip8b subunits. Optical mapping experiments showed that I(h) attenuated glutamatergic responses evoked across the apical and basal dendritic arbors of corticospinal but not corticostriatal neurons. Due to I(h), corticospinal neurons resonated, with a broad peak at ∼4 Hz, and were selectively modulated by α-adrenergic stimulation. I(h) reduced the summation of short trains of artificial excitatory postsynaptic potentials (EPSPs) injected at the soma, and similar effects were observed for short trains of actual EPSPs evoked from layer 2/3 neurons. I(h) narrowed the coincidence detection window for EPSPs arriving from separate layer 2/3 inputs, indicating that the dampening effect of I(h) extended to spatially disperse inputs. To test the role of corticospinal I(h) in transforming EPSPs into action potentials, we transfected layer 2/3 pyramidal neurons with channelrhodopsin-2 and used rapid photostimulation across multiple sites to synaptically drive spiking activity in postsynaptic neurons. Blocking I(h) increased layer 2/3-driven spiking in corticospinal but not corticostriatal neurons. Our results imply that I(h)-dependent synaptic integration in corticospinal neurons constitutes an intracortical control mechanism, regulating the efficacy with which local activity in motor cortex is transferred to downstream circuits in the spinal cord. We speculate that modulation of I(h) in corticospinal neurons could provide a microcircuit-level mechanism involved in translating action planning into action execution.

Publication types

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

MeSH terms

  • Action Potentials / physiology
  • Adrenergic Agonists / pharmacology
  • Animals
  • Corpus Callosum / cytology
  • Corpus Callosum / physiology
  • Cyclic Nucleotide-Gated Cation Channels / antagonists & inhibitors
  • Cyclic Nucleotide-Gated Cation Channels / genetics
  • Cyclic Nucleotide-Gated Cation Channels / physiology*
  • Dendrites / physiology
  • Efferent Pathways / cytology
  • Efferent Pathways / physiology*
  • Evoked Potentials, Motor / drug effects
  • Evoked Potentials, Motor / physiology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Female
  • Glutamic Acid / physiology
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Motor Cortex / cytology
  • Motor Cortex / physiology*
  • Organ Culture Techniques
  • Potassium Channels / genetics
  • Potassium Channels / physiology*
  • Pyramidal Cells / physiology
  • Pyramidal Tracts / cytology
  • Pyramidal Tracts / physiology*
  • Pyrimidines / pharmacology
  • RNA, Messenger / metabolism
  • Receptors, Adrenergic / physiology
  • Synapses / physiology


  • Adrenergic Agonists
  • Cyclic Nucleotide-Gated Cation Channels
  • Hcn1 protein, mouse
  • Hcn1 protein, rat
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Membrane Proteins
  • Pex5l protein, rat
  • Potassium Channels
  • Pyrimidines
  • RNA, Messenger
  • Receptors, Adrenergic
  • ICI D2788
  • Glutamic Acid