title: Medial premotor cortex shows a reduction in inhibitory markers and mediates recovery in a mouse model of focal stroke.
abstract: OBJECTIVE
  Motor recovery after ischemic stroke in primary motor cortex is thought to occur in part through training-enhanced reorganization in undamaged premotor areas, enabled by reductions in cortical inhibition. Here we used a mouse model of focal cortical stroke and a double-lesion approach to test the idea that a medial premotor area (medial agranular cortex [AGm]) reorganizes to mediate recovery of prehension, and that this reorganization is associated with a reduction in inhibitory interneuron markers.
  
  
  METHODS
  C57Bl/6 mice were trained to perform a skilled prehension task to an asymptotic level of performance after which they underwent photocoagulation-induced stroke in the caudal forelimb area. The mice were then retrained and inhibitory interneuron immunofluorescence was assessed in prechosen, anatomically defined neocortical areas. Mice then underwent a second photocoagulation-induced stroke in AGm.
  
  
  RESULTS
  Focal caudal forelimb area stroke led to a decrement in skilled prehension. Training-associated recovery of prehension was associated with a reduction in parvalbumin, calretinin, and calbindin expression in AGm. Subsequent infarction of AGm led to reinstatement of the original deficit.
  
  
  CONCLUSIONS
  We conclude that with training, AGm can reorganize after a focal motor stroke and serve as a new control area for prehension. Reduced inhibition may represent a marker for reorganization or it is necessary for reorganization to occur. Our mouse model, with all of the attendant genetic benefits, may allow us to determine at the cellular and molecular levels how behavioral training and endogenous plasticity interact to mediate recovery.
authors: Department of Neurology, the Johns Hopkins Hospital, Meyer 6-113, 600 N Wolfe St, Baltimore, MD 21287, USA. sz@jhmi.edu
authors: Steven R
authors: SR
authors: Zeiler
authors: Ellen M
authors: EM
authors: Gibson
authors: Robert E
authors: RE
authors: Hoesch
authors: Ming Y
authors: MY
authors: Li
authors: Paul F
authors: PF
authors: Worley
authors: Richard J
authors: RJ
authors: O'Brien
authors: John W
authors: JW
authors: Krakauer
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009044:Motor Cortex / Q000473:pathology* / Q000502:physiology*; D009048:Motor Skills / Q000502:physiology; D009433:Neural Inhibition / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology; D020127:Recovery of Function / Q000502:physiology*; D020521:Stroke / Q000473:pathology* / Q000503:physiopathology