title: Reorganization of Motor Cortex by Vagus Nerve Stimulation Requires Cholinergic Innervation.
abstract: BACKGROUND
  Vagus nerve stimulation (VNS) paired with forelimb training drives robust, specific reorganization of movement representations in the motor cortex. The mechanisms that underlie VNS-dependent enhancement of map plasticity are largely unknown. The cholinergic nucleus basalis (NB) is a critical substrate in cortical plasticity, and several studies suggest that VNS activates cholinergic circuitry.
  
  
  OBJECTIVE
  We examined whether the NB is required for VNS-dependent enhancement of map plasticity in the motor cortex.
  
  
  METHODS
  Rats were trained to perform a lever pressing task and then received injections of the immunotoxin 192-IgG-saporin to selectively lesion cholinergic neurons of the NB. After lesion, rats underwent five days of motor training during which VNS was paired with successful trials. At the conclusion of behavioral training, intracortical microstimulation was used to document movement representations in motor cortex.
  
  
  RESULTS
  VNS paired with forelimb training resulted in a substantial increase in the representation of proximal forelimb in rats with an intact NB compared to untrained controls. NB lesions prevent this VNS-dependent increase in proximal forelimb area and result in representations similar to untrained controls. Motor performance was similar between groups, suggesting that differences in forelimb function cannot account for the difference in proximal forelimb representation.
  
  
  CONCLUSIONS
  Together, these findings indicate that the NB is required for VNS-dependent enhancement of plasticity in the motor cortex and may provide insight into the mechanisms that underlie the benefits of VNS therapy.
authors.affiliation: School of Behavioral Brain Sciences, The University of Texas at Dallas, 800 West Campbell Road, GR41, Richardson, TX 75080-3021, USA.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Hulsey
authors.affiliation: School of Behavioral Brain Sciences, The University of Texas at Dallas, 800 West Campbell Road, GR41, Richardson, TX 75080-3021, USA; Erik Jonsson School of Engineering and Computer Science, The University of Texas at Dallas, 800 West Campbell Road, Richardson, TX 75080-3021, USA; Texas Biomedical Device Center, The University of Texas at Dallas, 800 West Campbell Road, Richardson, TX 75080-3021, USA. Electronic address: seth.hays@utdallas.edu.
authors.forename: Seth A
authors.initials: SA
authors.lastname: Hays
authors.affiliation: School of Behavioral Brain Sciences, The University of Texas at Dallas, 800 West Campbell Road, GR41, Richardson, TX 75080-3021, USA; Texas Biomedical Device Center, The University of Texas at Dallas, 800 West Campbell Road, Richardson, TX 75080-3021, USA.
authors.forename: Navid
authors.initials: N
authors.lastname: Khodaparast
authors.affiliation: Texas Biomedical Device Center, The University of Texas at Dallas, 800 West Campbell Road, Richardson, TX 75080-3021, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ruiz
authors.affiliation: Erik Jonsson School of Engineering and Computer Science, The University of Texas at Dallas, 800 West Campbell Road, Richardson, TX 75080-3021, USA.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Das
authors.affiliation: School of Behavioral Brain Sciences, The University of Texas at Dallas, 800 West Campbell Road, GR41, Richardson, TX 75080-3021, USA; Erik Jonsson School of Engineering and Computer Science, The University of Texas at Dallas, 800 West Campbell Road, Richardson, TX 75080-3021, USA; Texas Biomedical Device Center, The University of Texas at Dallas, 800 West Campbell Road, Richardson, TX 75080-3021, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Rennaker
authors.affiliation: School of Behavioral Brain Sciences, The University of Texas at Dallas, 800 West Campbell Road, GR41, Richardson, TX 75080-3021, USA; Texas Biomedical Device Center, The University of Texas at Dallas, 800 West Campbell Road, Richardson, TX 75080-3021, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Kilgard
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000633:toxicity; D020532:Basal Nucleus of Meynert / Q000166:cytology / Q000502:physiology; D059329:Cholinergic Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D005260:Female; D009044:Motor Cortex / Q000166:cytology* / Q000502:physiology*; D009068:Movement / Q000502:physiology; D009473:Neuronal Plasticity; D051381:Rats; D017207:Rats, Sprague-Dawley; D054789:Ribosome Inactivating Proteins, Type 1 / Q000633:toxicity; D000076985:Saporins; D055536:Vagus Nerve Stimulation
chemical_list: C085696:192 IgG-saporin; D000911:Antibodies, Monoclonal; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins
keywords: Acetylcholine; Cortical plasticity; Cortical reorganization; Immunotoxin; Motor cortex; Motor training; Nucleus basalis; Vagal nerve stimulation; Vagus nerve stimulation
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