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

Patrick Sheets, Benjamin A. Suter, Taro Kiritani, C. S. Savio Chan, D. James Surmeier, Gordon M G Shepherd

Research output: Contribution to journalArticle

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Abstract

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 hyperpolarizationactivated 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 Ih 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.

Original languageEnglish (US)
Pages (from-to)2216-2231
Number of pages16
JournalJournal of Neurophysiology
Volume106
Issue number5
DOIs
StatePublished - Nov 2011
Externally publishedYes

Fingerprint

Motor Cortex
Neurons
Excitatory Postsynaptic Potentials
Pyramidal Cells
Rodent Control
Neocortex
Carisoprodol
Adrenergic Agents
Nervous System
Action Potentials
Mammals
Spinal Cord
Messenger RNA
Brain

Keywords

  • Corticospinal
  • Cyclic
  • Hyperpolarization-activated
  • Pyramidal neuron

ASJC Scopus subject areas

  • Physiology
  • Neuroscience(all)

Cite this

Corticospinal-specific HCN expression in mouse motor cortex : I h)-dependent synaptic integration as a candidate microcircuit mechanism involved in motor control. / Sheets, Patrick; Suter, Benjamin A.; Kiritani, Taro; Savio Chan, C. S.; James Surmeier, D.; Shepherd, Gordon M G.

In: Journal of Neurophysiology, Vol. 106, No. 5, 11.2011, p. 2216-2231.

Research output: Contribution to journalArticle

Sheets, Patrick ; Suter, Benjamin A. ; Kiritani, Taro ; Savio Chan, C. S. ; James Surmeier, D. ; Shepherd, Gordon M G. / Corticospinal-specific HCN expression in mouse motor cortex : I h)-dependent synaptic integration as a candidate microcircuit mechanism involved in motor control. In: Journal of Neurophysiology. 2011 ; Vol. 106, No. 5. pp. 2216-2231.
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