Reliability in the location of hindlimb motor representations in Fischer-344 rats

Laboratory investigation

Restricted access

Object

The purpose of the present study was to determine the feasibility of using a common laboratory rat strain for reliably locating cortical motor representations of the hindlimb.

Methods

Intracortical microstimulation techniques were used to derive detailed maps of the hindlimb motor representations in 6 adult Fischer-344 rats.

Results

The organization of the hindlimb movement representation, while variable across individual rats in topographic detail, displayed several commonalities. The hindlimb representation was positioned posterior to the forelimb motor representation and posterolateral to the motor trunk representation. The areal extent of the hindlimb representation across the cortical surface averaged 2.00 ± 0.50 mm2. Superimposing individual maps revealed an overlapping area measuring 0.35 mm2, indicating that the location of the hindlimb representation can be predicted reliably based on stereotactic coordinates. Across the sample of rats, the hindlimb representation was found 1.25–3.75 mm posterior to the bregma, with an average center location approximately 2.6 mm posterior to the bregma. Likewise, the hindlimb representation was found 1–3.25 mm lateral to the midline, with an average center location approximately 2 mm lateral to the midline.

Conclusions

The location of the cortical hindlimb motor representation in Fischer-344 rats can be reliably located based on its stereotactic position posterior to the bregma and lateral to the longitudinal skull suture at midline. The ability to accurately predict the cortical localization of functional hindlimb territories in a rodent model is important, as such animal models are being increasingly used in the development of brain-computer interfaces for restoration of function after spinal cord injury.

Abbreviations used in this paper:ICMS = intracortical microstimulation; SCI = spinal cord injury.

Article Information

Address correspondence to: Shawn B. Frost, Ph.D., Department of Molecular & Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Blvd., MS 4016, Kansas City, Kansas 66160. email: sfrost@kumc.edu.

Please include this information when citing this paper: published online May 31, 2013; DOI: 10.3171/2013.4.SPINE12961.

© AANS, except where prohibited by US copyright law.

Headings

Figures

  • View in gallery

    A: Schematic diagram of a dorsolateral view of the rat brain showing the location of the hindlimb representation (HL) relative to the forelimb (FL) and face representations in primary motor cortex (M1) of the left hemisphere. B = position of the bregma on the dorsal surface of the skull at midline over the longitudinal convexity. B: Results of ICMS mapping of the hindlimb representation in the left hemisphere in a representative Fischer-344 rat (R33). Circles represent the location of microelectrode penetrations and colors represent the movement evoked by near-threshold electrical stimulation (< 60 μA). In this rat the total hindlimb area measures 2.51 mm2. A = anterior; P = posterior. C: Results of ICMS mapping experiments in the remaining 5 rats. Area measurements of hindlimb movement representations are listed in Table 1. M = medial. The 1-mm scale bar applies to all maps.

  • View in gallery

    Graphs showing the distribution of minimum currents required to evoke hindlimb movements (movement thresholds) in each of the 6 rats. Current values for each map were normalized across the range of currents from minimum to maximum, such that minimum (lowest) thresholds = 1 and appear in red and maximum (highest) thresholds = 0 and appear in blue. A MATLAB algorithm was used to interpolate values to create a continuous distribution. A = anterior; L = lateral; M = medial; P = posterior.

  • View in gallery

    Left: Overlay of hindlimb representation borders relative to bregma for each rat. Borders are derived from movement maps illustrated in Fig. 1B and C, and are created by a smoothing algorithm based on locations of individual boundary sites. Right: Hindlimb probability map showing the degree of overlap of hindlimb representations in the sample of 6 rats. Shades of gray and values indicate the number of rats with hindlimb representation at a particular stereotactic location. The darkest region (6) represents the territory in which hindlimb movements are evoked in all 6 rats (100%). The center of the overlap region is located at 2.00 mm posterior and 2.64 mm lateral to the bregma. A = anterior; L = lateral; M = medial; P = posterior.

References

1

Angel AJolly AILemon RN: A re-investigation of the sensorimotor cortical area for the hind leg in the rat. J Physiol 215:18P19P1971

2

Barth TMJones TASchallert T: Functional subdivisions of the rat somatic sensorimotor cortex. Behav Brain Res 39:73951990

3

Benton RLWhittemore SR: VEGF165 therapy exacerbates secondary damage following spinal cord injury. Neurochem Res 28:169317032003

4

Cenci MAWhishaw IQSchallert T: Animal models of neurological deficits: how relevant is the rat?. Nat Rev Neurosci 3:5745792002

5

Donoghue JPWise SP: The motor cortex of the rat: cytoarchitecture and microstimulation mapping. J Comp Neurol 212:76881982

6

Ethier COby ERBauman MJMiller LE: Restoration of grasp following paralysis through brain-controlled stimulation of muscles. Nature 485:3683712012

7

Friel KMNudo RJ: Recovery of motor function after focal cortical injury in primates: compensatory movement patterns used during rehabilitative training. Somatosens Mot Res 15:1731891998

8

Hall RDLindholm EP: Organization of motor and somatosensory neocortex in the albino rat. Brain Res 66:23381974

9

Hochberg LRBacher DJarosiewicz BMasse NYSimeral JDVogel J: Reach and grasp by people with tetraplegia using a neurally controlled robotic arm. Nature 485:3723752012

10

Hollis ER IILu PBlesch ATuszynski MH: IGF-I gene delivery promotes corticospinal neuronal survival but not regeneration after adult CNS injury. Exp Neurol 215:53592009

11

Huang CSSirisko MAHiraba HMurray GMSessle BJ: Organization of the primate face motor cortex as revealed by intracortical microstimulation and electrophysiological identification of afferent inputs and corticobulbar projections. J Neurophysiol 59:7968181988

12

Jurkiewicz MTMikulis DJMcIlroy WEFehlings MGVerrier MC: Sensorimotor cortical plasticity during recovery following spinal cord injury: a longitudinal fMRI study. Neurorehabil Neural Repair 21:5275382007

13

Kleim JABarbay SNudo RJ: Functional reorganization of the rat motor cortex following motor skill learning. J Neurophysiol 80:332133251998

14

Kokotilo KJEng JJCurt A: Reorganization and preservation of motor control of the brain in spinal cord injury: a systematic review. J Neurotrauma 26:211321262009

15

Loy DNCrawford CHDarnall JBBurke DAOnifer SMWhittemore SR: Temporal progression of angiogenesis and basal lamina deposition after contusive spinal cord injury in the adult rat. J Comp Neurol 445:3083242002

16

Master DCowan TNarayan SKirsch RHoyen H: Involuntary, electrically excitable nerve transfer for denervation: results from an animal model. J Hand Surg Am 34:479487487.e1487.e32009

17

Neafsey EJBold ELHaas GHurley-Gius KMQuirk GSievert CF: The organization of the rat motor cortex: a microstimulation mapping study. Brain Res 396:77961986

18

Nudo RJFrost SBThe evolution of motor cortex and motor systems. Kaas JH: Evolution of Nervous Systems: A Comparative Reference OxfordElsevier3:2006. 374395

19

Nudo RJJenkins WMMerzenich MMPrejean TGrenda R: Neurophysiological correlates of hand preference in primary motor cortex of adult squirrel monkeys. J Neurosci 12:291829471992

20

Nudo RJMasterton RB: Descending pathways to the spinal cord: a comparative study of 22 mammals. J Comp Neurol 277:53791988

21

Nudo RJMilliken GWJenkins WMMerzenich MM: Use-dependent alterations of movement representations in primary motor cortex of adult squirrel monkeys. J Neurosci 16:7858071996

22

Sabbah Pde Schonen SLeveque CGay SPfefer FNioche C: Sensorimotor cortical activity in patients with complete spinal cord injury: a functional magnetic resonance imaging study. J Neurotrauma 19:53602002

23

Sandner BPillai DRHeidemann RMSchuierer GMueller MFBogdahn U: In vivo high-resolution imaging of the injured rat spinal cord using a 3.0T clinical MR scanner. J Magn Reson Imaging 29:7257302009

24

Settlage PHBinghan WGSuckle HMBorge AFWoolsey CN: The pattern of localization in the motor cortex of the rat. Fed Proc 8:1441949

25

Stoney SD JrThompson WDAsanuma H: Excitation of pyramidal tract cells by intracortical microstimulation: effective extent of stimulating current. J Neurophysiol 31:6596691968

26

Tyler BMHdeib ACaplan JLegnani FGFowers KDBrem H: Delayed onset of paresis in rats with experimental intramedullary spinal cord gliosarcoma following intratumoral administration of the paclitaxel delivery system OncoGel. Laboratory investigation. J Neurosurg Spine 16:931012012

27

VandenBerg PMHogg TMKleim JAWhishaw IQ: Long-Evans rats have a larger cortical topographic representation of movement than Fischer-344 rats: a microstimulation study of motor cortex in naïve and skilled reaching-trained rats. Brain Res Bull 59:1972032002

28

Weber TVroemen MBehr VNeuberger TJakob PHaase A: In vivo high-resolution MR imaging of neuropathologic changes in the injured rat spinal cord. AJNR Am J Neuroradiol 27:5986042006

29

Woolsey CNOrganization of somatic sensory and motor areas of the cerebral cortex. Harlow HFWoolsey CN: Biological and Biochemical Bases of Behavior Madison, WIUniversity of Wisconsin Press1958. 6381

30

Woolsey CNPatterns of localization in sensory and motor areas of the cerebral cortex. Cobb S: Biology Of Mental Health and Disease New YorkHoeber1952. 193206

TrendMD

Metrics

Metrics

All Time Past Year Past 30 Days
Abstract Views 30 30 7
Full Text Views 52 52 9
PDF Downloads 171 171 35
EPUB Downloads 0 0 0

PubMed

Google Scholar