title: Intracortical Microstimulation (ICMS) Activates Motor Cortex Layer 5 Pyramidal Neurons Mainly Transsynaptically.
abstract: BACKGROUND
  Intracortical microstimulation (ICMS) is a technique used for a number of purposes including the derivation of cortical movement representations (motor maps). Its application can activate the output layer 5 of motor cortex and can result in the elicitation of body movements depending upon the stimulus parameters used.
  
  
  OBJECTIVE
  The extent to which pyramidal tract projection neurons of the motor cortex are activated transsynaptically or directly by ICMS remains an open question. Given this uncertainty in the mode of activation, we used a preparation that combined patch clamp whole-cell recordings from single layer 5 pyramidal neurons and extracellular ICMS in slices of motor cortex as well as a standard in vivo mapping technique to ask how ICMS activated motor cortex pyramidal neurons.
  
  
  METHODS
  We measured changes in synaptic spike threshold and spiking rate to ICMS in vitro and movement threshold in vivo in the presence or absence of specific pharmacological blockers of glutamatergic (AMPA, NMDA and Kainate) receptors and GABAA receptors.
  
  
  RESULTS
  With major excitatory and inhibitory synaptic transmission blocked (with DNQX, APV and bicuculline methiodide), we observed a significant increase in the ICMS current intensity required to elicit a movement in vivo as well as to the first spike and an 85% reduction in spiking responses in vitro. Subsets of neurons were still responsive after the synaptic block, especially at higher current intensities, suggesting a modest direct activation.
  
  
  CONCLUSIONS
  Taken together our data indicate a mainly synaptic mode of activation to ICMS in layer 5 of rat motor cortex.
authors.affiliation: Hotchkiss Brain Institute, University of Calgary, Alberta, Canada T2N 4N1; Department of Neuroscience, University of Calgary, Alberta, Canada T2N 4N1.
authors.forename: Ahmed T
authors.initials: AT
authors.lastname: Hussin
authors.affiliation: Hotchkiss Brain Institute, University of Calgary, Alberta, Canada T2N 4N1; Department of Neuroscience, University of Calgary, Alberta, Canada T2N 4N1; Department of Physiology and Pharmacology, University of Calgary, Alberta, Canada T2N 4N1; Department of Cell Biology and Anatomy, University of Calgary, Alberta, Canada T2N 4N1.
authors.forename: Jeffery A
authors.initials: JA
authors.lastname: Boychuk
authors.affiliation: Hotchkiss Brain Institute, University of Calgary, Alberta, Canada T2N 4N1; Department of Neuroscience, University of Calgary, Alberta, Canada T2N 4N1.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Brown
authors.affiliation: Hotchkiss Brain Institute, University of Calgary, Alberta, Canada T2N 4N1; Department of Neuroscience, University of Calgary, Alberta, Canada T2N 4N1; Department of Physiology and Pharmacology, University of Calgary, Alberta, Canada T2N 4N1.
authors.forename: Quentin J
authors.initials: QJ
authors.lastname: Pittman
authors.affiliation: Hotchkiss Brain Institute, University of Calgary, Alberta, Canada T2N 4N1; Department of Neuroscience, University of Calgary, Alberta, Canada T2N 4N1; Department of Physiology and Pharmacology, University of Calgary, Alberta, Canada T2N 4N1; Department of Cell Biology and Anatomy, University of Calgary, Alberta, Canada T2N 4N1. Electronic address: gteskey@ucalgary.ca.
authors.forename: G Campbell
authors.initials: GC
authors.lastname: Teskey
mesh_terms: D000818:Animals; D001640:Bicuculline / Q000031:analogs & derivatives / Q000494:pharmacology; D001931:Brain Mapping / Q000379:methods; D004558:Electric Stimulation / Q000379:methods*; D008297:Male; D009044:Motor Cortex / Q000502:physiology*; D009068:Movement / Q000502:physiology*; D017966:Pyramidal Cells / Q000502:physiology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D011810:Quinoxalines; C017069:bicuculline methiodide; C056723:FG 9041; C056639:2-amino-5-phosphopentanoic acid; D014633:Valine; D001640:Bicuculline
keywords: Intracortical microstimulation; Motor cortex; Motor maps; Movement representations; Patch-clamping; Rat