Skip to main content

An Approach to Understanding the Neural Circuitry of Saccade Control in the Cerebral Cortex Using Antidromic Identification in the Awake Behaving Macaque Monkey Model

  • Protocol
  • First Online:
Animal Models of Movement Disorders

Part of the book series: Neuromethods ((NM,volume 62))

Abstract

Saccadic eye movements are rapid conjugate movements of the eyes made to align the visual axis with objects of interest. Such movements are some of the most precise and well-controlled motor responses of which the nervous system is capable, and they display an enormous range of flexibility. Because saccades are controlled by a distributed network of brain areas including the cerebral cortex, basal ganglia, cerebellum, and brainstem, investigation of deficits in saccade control in movement disorders such as Huntington’s and Parkinson’s disease provide a potential window into their underlying neuropathology. A full understanding of pathological changes requires detailed investigations of the neural mechanisms of saccade control in the cerebral cortex. This requires invasive methods, which necessitate the use of an animal model. Here, we describe the rationale and use of the awake-behaving rhesus macaque model for the investigation of cortical control of eye movements. We focus on the technique of single neuron recording, particularly the use of antidromic identification of cortical projection neurons. Investigations of the circuit properties of the oculomotor system using this technique promise to provide unique insights into the neuropathology of movement disorders.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Lasker AG, Zee DS (1997) Ocular motor abnormalities in Huntington’s disease. Vision Res 37: 3639

    Article  PubMed  CAS  Google Scholar 

  2. Briand KA, Strallow D, Hening W, Poizner H, Sereno AB (1999) Control of voluntary and reflexive saccades in Parkinson’s disease. Exp Brain Res 129: 38

    Article  PubMed  CAS  Google Scholar 

  3. Hess WR, Burgi S, Bucher V (1946) Motor function of tectal and tegmental area. Monatsschr Psychiatr Neurol 112: 1

    Article  PubMed  CAS  Google Scholar 

  4. Hallett PE (1978) Primary and secondary saccades to goals defined by instructions. Vision Res 18: 1279–1296

    Article  PubMed  CAS  Google Scholar 

  5. Everling S, Fischer B (1998) The antisaccade: a review of basic research and clinical studies. Neuropsychologia 36: 885–899

    Article  PubMed  CAS  Google Scholar 

  6. Leigh RJ, Zee DS (2006) The neurology of eye movements. Oxford University Press, Oxford

    Google Scholar 

  7. Munoz DP, Dorris MC, Pare M, Everling S (2000) On your mark, get set: brainstem circuitry underlying saccadic initiation. Can J Physiol Pharmacol 78: 934

    Article  PubMed  CAS  Google Scholar 

  8. Sparks DL (2002) The brainstem control of saccadic eye movements. Nat Rev Neurosci 3: 952

    Article  PubMed  CAS  Google Scholar 

  9. Hubel DH (1958) Cortical unit responses to visual stimuli in nonanesthetized cats. Am J Ophthalmol 46: 110–121; discussion 121–112

    Google Scholar 

  10. Jasper H, Ricci G, Doane B (1960) Microelectrode analysis of cortical cell discharge during avoidance conditioning in the monkey. Int J Electroencephalogr Clin Neurophsyiol Suppl 131: 137–156

    Google Scholar 

  11. Evarts EV (1966) Pyramidal tract activity associated with a conditioned hand movement in the monkey. J Neurophysiol 29: 1011–1027

    PubMed  CAS  Google Scholar 

  12. Ferrier D (1876) The functions of the brain. Smith, Elder & Co., London

    Google Scholar 

  13. Horlsey VA, Schaefer EA (1888) Experimental Researches in Cerebral Physiology. II. On the Muscular Contractions Which Are Evoked by Excitation of the Motor Tract. Philos Trans R Soc Lond B Biol Sci 39: 404–409

    Google Scholar 

  14. Mott FW, Schaefer EA (1890) On associated eye-movements produced by cortical faradization of the monkey’s brain. Brain 13: 165–173

    Article  Google Scholar 

  15. Levinsohn G (1909) Über die Beziehungen der Grosshirnrinde beim Affebn zu den Bewegungen des Auges. Archiv für Opthalmologie 71: 313–378

    Article  Google Scholar 

  16. Robinson DA, Fuchs AF (1969) Eye movements evoked by stimulation of frontal eye fields. J Neurophysiol 32: 637

    PubMed  CAS  Google Scholar 

  17. Penfield W, Boldrey E (1937) Somatic motor and sensory representation in the cerebral cortex of man as studied by electrical stimulation. Brain 60: 389–443

    Article  Google Scholar 

  18. Foerster O (1931) The cerebral cortex in man. The Lancet 218: 309–312

    Article  Google Scholar 

  19. Bizzi E (1968) Discharge of frontal eye field neurons during saccadic and following eye movements in unanesthetized monkeys. Exp Brain Res 6: 69–80

    Article  PubMed  CAS  Google Scholar 

  20. Bizzi E, Schiller PH (1970) Single unit activity in the frontal eye fields of unanesthetized monkeys during eye and head movement. Exp Brain Res 10: 150–158

    Article  PubMed  CAS  Google Scholar 

  21. Mohler CW, Goldberg ME, Wurtz RH (1973) Visual receptive fields of frontal eye field neurons. Brain Res 61: 385–389

    Article  PubMed  CAS  Google Scholar 

  22. Wurtz RH, Mohler CW (1976) Enhancement of visual responses in monkey striate cortex and frontal eye fields. J Neurophysiol 39: 766

    PubMed  CAS  Google Scholar 

  23. Bruce CJ, Goldberg ME (1985) Primate frontal eye fields. I. Single neurons discharging before saccades. J Neurophysiol 53: 603

    Google Scholar 

  24. Hanes DP, Schall JD (1996) Neural control of voluntary movement initiation. Science 274: 427

    Article  PubMed  CAS  Google Scholar 

  25. Brown JW, Hanes DP, Schall JD, Stuphorn V (2008) Relation of frontal eye field activity to saccade initiation during a countermanding task. Exp Brain Res 190: 135–151

    Article  PubMed  Google Scholar 

  26. Hanes DP, Wurtz RH (2001) Interaction of the frontal eye field and superior colliculus for saccade generation. J Neurophysiol 85: 804–815

    PubMed  CAS  Google Scholar 

  27. Evarts EV, Shinoda Y, Wise SP (1984) Neurophysiological approaches to higher brain function. In. Wiley, New York

    Google Scholar 

  28. Humphrey D, Schmidt E (1990) Extracellular single-unit recording methods. In: Boulton A, Baker G, Vanderwold C (eds) Neurophysiological Techniques Applications to Neural Systems, vol 15. The Humana Press Inc, Clifton, NJ

    Google Scholar 

  29. Lipski J (1981) Antidromic activation of ­neurons as an analytic tool in the study of the central nervous system. J Neurosci Methods 4: 1–32

    Article  PubMed  CAS  Google Scholar 

  30. Swadlow HA (1998) Neocortical efferent neurons with very slowly conducting axons: strategies for reliable antidromic identification. J Neurosci Methods 79: 131–141

    Article  PubMed  CAS  Google Scholar 

  31. Gasser H, Erlanger J (1925) The nature of conduction of an impulse in the relatively refractory period. Am J Physiol 73: 613–635

    Google Scholar 

  32. Paintal A (1959) Intramuscular propagation of sensory impulses. J Physiol London 148: 240–251

    PubMed  CAS  Google Scholar 

  33. Bishop PO, Burke W, Davis R (1962) The interpretation of the extracellular response of single lateral geniculate cells. J Physiol 162: 451–472

    PubMed  CAS  Google Scholar 

  34. Darian-Smith I, Phillips G, Ryan RD (1963) Functional Organization in the Trigeminal Main Sensory and Rostral Spinal Nuclei of the Cat. J Physiol 168: 129–146

    PubMed  CAS  Google Scholar 

  35. Fuller JH, Schlag JD (1976) Determination of antidromic excitation by the collision test: problems of interpretation. Brain Res 112: 283–298

    Article  PubMed  CAS  Google Scholar 

  36. Tasaki I (1949) Collision of two nerve impulses in the nerve fibre. Biochem Biophys Acta Amst 3: 494–497

    Article  Google Scholar 

  37. Johnston K, Everling S (2006) Monkey dorsolateral prefrontal cortex sends task-selective signals directly to the superior colliculus. J Neurosci 26: 12471–12478

    Article  PubMed  CAS  Google Scholar 

  38. Johnston K, Everling S (2009) Task-relevant output signals are sent from monkey dorsolateral prefrontal cortex to the superior colliculus during a visuospatial working memory task. J Cogn Neurosci 21: 1023–1038

    Article  PubMed  Google Scholar 

  39. Pare M, Wurtz RH (1997) Monkey posterior parietal cortex neurons antidromically activated from superior colliculus. J Neurophysiol 78: 3493

    PubMed  CAS  Google Scholar 

  40. Segraves MA, Goldberg ME (1987) Functional properties of corticotectal neurons in the monkey’s frontal eye field. J Neurophysiol 58: 1387

    PubMed  CAS  Google Scholar 

  41. Everling S, Munoz DP (2000) Neuronal correlates for preparatory set associated with pro-saccades and antisaccades in the primate frontal eye field. J Neurosci 20: 387–400

    PubMed  CAS  Google Scholar 

  42. Sommer MA, Wurtz RH (2000) Composition and topographic organization of signals sent from the frontal eye field to the superior colliculus. J Neurophysiol 83: 1979

    PubMed  CAS  Google Scholar 

  43. Wurtz RH, Sommer MA, Pare M, Ferraina S (2001) Signal transformations from cerebral cortex to superior colliculus for the generation of saccades. Vision Res 41: 3399–3412

    Article  PubMed  CAS  Google Scholar 

  44. Sommer MA, Wurtz RH (2002) A pathway in primate brain for internal monitoring of movements. Science 296: 1480–1482

    Article  PubMed  CAS  Google Scholar 

  45. Sommer MA, Wurtz RH (2004) What the brain stem tells the frontal cortex. I. Oculomotor signals sent from superior colliculus to frontal eye field via mediodorsal thalamus. J Neurophysiol 91: 1381–1402

    Google Scholar 

  46. Pare M, Wurtz RH (2001) Progression in neuronal processing for saccadic eye ­movements from parietal cortex area lip to superior colliculus. J Neurophysiol 85: 2545

    PubMed  CAS  Google Scholar 

  47. Ferraina S, Pare M, Wurtz RH (2002) Comparison of cortico-cortical and cortico-collicular signals for the generation of saccadic eye movements. J Neurophysiol 87: 845

    PubMed  Google Scholar 

  48. Johnston K, De Souza JFX, Everling S (2009) Monkey prefrontal cortical pyramidal and putative interneurons exhibit differential patterns of activity between pro- and antisaccade tasks. J Neurosci 29: 5516–5524

    Article  PubMed  CAS  Google Scholar 

  49. Shin SY, Sommer MA (2006) Frontal eye field input neurons have higher spontaneous firing rates and narrower action potentials than output neurons. In: Society for Neuroscience Abstracts, vol Program No. 138.11. Society for Neuroscience, Atlanta, GA

    Google Scholar 

  50. Jones EG (1984) Laminar distribution of cortical efferent cells. In: Peters A, Jones EG (eds) Cerebral Cortex. Plenum Press, New York, pp 521–553

    Google Scholar 

  51. Fuchs AF (1967) Saccadic and smooth pursuit eye movements in the monkey. J Physiol 191: 609–631

    PubMed  CAS  Google Scholar 

  52. Emeric EE, Brown JW, Boucher L, Carpenter RH, Hanes DP, Harris R, Logan GD, Mashru RN, Pare M, Pouget P, Stuphorn V, Taylor TL, Schall JD (2007) Influence of history on saccade countermanding performance in humans and macaque monkeys. Vision Res 47: 35–49

    Article  PubMed  Google Scholar 

  53. Bell AH, Everling S, Munoz DP (2000) Influence of stimulus eccentricity and direction on characteristics of pro- and antisaccades in non-human primates. J Neurophysiol 84: 2595–2604

    PubMed  CAS  Google Scholar 

  54. Kaas JH, Huerta MF (1988) The subcortical visual system of primates. In: Steklis HD, Erwin J (eds) Comparative Primate Biology, vol 4: Neurosciences. Alan R. Liss, New York, pp 327–391

    Google Scholar 

  55. Leichnetz GR, Spencer RF, Hardy SG, Astruc J (1981) The prefrontal corticotectal projection in the monkey; an anterograde and retrograde horseradish peroxidase study. Neuroscience 6: 1023

    Article  PubMed  CAS  Google Scholar 

  56. Fries W (1984) Cortical projections to the superior colliculus in the macaque monkey: a retrograde study using horseradish peroxidase. J Comp Neurol 230: 55

    Article  PubMed  CAS  Google Scholar 

  57. Preuss TM (2007) Evolutionary specializations of primate brain systems. In: Rovosa MJ, Dagosto M (eds) Primate Origins: Evolution and Adaptations. Springer, New York

    Google Scholar 

  58. Koyama M, Hasegawa I, Osada T, Adachi Y, Nakahara K, Miyashita Y (2004) Functional magnetic resonance imaging of macaque monkeys performing visually guided saccade tasks: comparison of cortical eye fields with humans. Neuron 41: 795

    Article  PubMed  CAS  Google Scholar 

  59. Baker JT, Patel GH, Corbetta M, Snyder LH (2005) Distribution of Activity Across the Monkey Cerebral Cortical Surface, Thalamus and Midbrain during Rapid, Visually Guided Saccades. Cereb Cortex 16: 447–459

    Article  PubMed  Google Scholar 

  60. Orban GA, Claeys K, Nelissen K, Smans R, Sunaert S, Todd JT, Wardak C, Durand JB, Vanduffel W (2006) Mapping the parietal cortex of human and non-human primates. Neuropsychologia 44: 2647–2667

    Article  PubMed  Google Scholar 

  61. Ford KA, Gati JS, Menon RS, Everling S (2009) BOLD fMRI activation for anti-saccade in nonhuman primates. Neuroimage 45: 470–476

    Article  PubMed  Google Scholar 

  62. Petrides M, Pandya DN (2002) Comparative cytoarchitectonic analysis of the human and the macaque ventrolateral prefrontal cortex and corticocortical connection patterns in the monkey. Eur J Neurosci 16: 291–310

    Article  PubMed  CAS  Google Scholar 

  63. Petrides M, Pandya DN (1999) Dorsolateral prefrontal cortex: comparative cytoarchitectonic analysis in the human and the macaque brain and corticocortical connection patterns. Eur J Neurosci 11: 1011–1036

    Article  PubMed  CAS  Google Scholar 

  64. Paus T (1996) Location and function of the human frontal eye-field: a selective review. Neuropsychologia 34: 475–483

    Article  PubMed  CAS  Google Scholar 

  65. Amiez C, Kostopoulos P, Champod AS, Petrides M (2006) Local morphology predicts functional organization of the dorsal premotor region in the human brain. J Neurosci 26: 2724–2731

    Article  PubMed  CAS  Google Scholar 

  66. Rosano C, Sweeney JA, Melchitzky DS, Lewis DA (2003) The human precentral sulcus: chemoarchitecture of a region corresponding to the frontal eye fields. Brain Res 972: 16–30

    Article  PubMed  CAS  Google Scholar 

  67. Preuss TM (2000) Taking the measure of diversity: comparative alternatives to the model-animal paradigm in cortical neuroscience. Brain Behav Evol 55: 287–299

    Article  PubMed  CAS  Google Scholar 

  68. Passingham R (2009) How good is the macaque monkey model of the human brain? Curr Opin Neurobiol 19: 6–11

    Article  PubMed  CAS  Google Scholar 

  69. Saslow MG (1967) Effects of components of displacement-step stimuli upon latency of saccadic eye movements. J Opt Soc Am 57: 1024

    Article  PubMed  CAS  Google Scholar 

  70. Fischer B, Boch R, Ramsperger E (1984) Express-saccades of the monkey: effect of daily training on probability of occurrence and reaction time. Exp Brain Res 55: 232

    Article  PubMed  CAS  Google Scholar 

  71. Fischer B, Ramsperger E (1984) Human express saccades: extremely short reaction times of goal directed eye movements. ExpBrain Res 57: 191

    CAS  Google Scholar 

  72. Fischer B, Ramsperger E (1986) Human express saccades: effects of randomization and daily practice. Exp Brain Res 64: 569

    Article  PubMed  CAS  Google Scholar 

  73. Pare M, Munoz DP (1996) Saccadic reaction time in the monkey: advanced preparation of oculomotor programs is primarily responsible for express saccade occurrence. J Neurophysiol 76: 3666

    PubMed  CAS  Google Scholar 

  74. Fischer B, Boch R (1983) Saccadic eye movements after extremely short reaction times in the monkey. Brain Res 260: 21

    Article  PubMed  CAS  Google Scholar 

  75. Dias EC, Bruce CJ (1994) Physiological correlate of fixation disengagement in the primate’s frontal eye field. J Neurophysiol 72: 2532

    PubMed  CAS  Google Scholar 

  76. Tinsley CJ, Everling S (2002) Contribution of the primate prefrontal cortex to the gap effect. Prog Brain Res 140: 61

    Article  PubMed  Google Scholar 

  77. Ben Hamed S, Duhamel JR (2002) Ocular fixation and visual activity in the monkey lateral intraparietal area. Exp Brain Res 142: 512

    Article  PubMed  CAS  Google Scholar 

  78. Dorris MC, Munoz DP (1995) A neural correlate for the gap effect on saccadic reaction times in monkey. J Neurophysiol 73: 2558

    PubMed  CAS  Google Scholar 

  79. Dorris MC, Pare M, Munoz DP (1997) Neuronal activity in monkey superior colliculus related to the initiation of saccadic eye movements. J Neurosci 17: 8566

    PubMed  CAS  Google Scholar 

  80. Hikosaka O, Wurtz RH (1983) Visual and oculomotor functions of monkey substantia nigra pars reticulata. III. Memory-contingent visual and saccade responses. J Neurophysiol 49: 1268

    Google Scholar 

  81. Gnadt JW, Andersen RA (1988) Memory related motor planning activity in posterior parietal cortex of macaque. Exp Brain Res 70: 216

    PubMed  CAS  Google Scholar 

  82. Funahashi S, Bruce CJ, Goldman-Rakic PS (1989) Mnemonic coding of visual space in the monkey’s dorsolateral prefrontal cortex. J Neurophysiol 61: 331

    PubMed  CAS  Google Scholar 

  83. Funahashi S, Bruce CJ, Goldman-Rakic PS (1990) Visuospatial coding in primate prefrontal neurons revealed by oculomotor paradigms. J Neurophysiol 63: 814

    PubMed  CAS  Google Scholar 

  84. Funahashi S, Bruce CJ, Goldman-Rakic PS (1991) Neuronal activity related to saccadic eye movements in the monkey’s dorsolateral prefrontal cortex. J Neurophysiol 65: 1464

    PubMed  CAS  Google Scholar 

  85. Stuphorn V, Brown JW, Schall JD (2010) Role of supplementary eye field in saccade initiation: executive, not direct, control. J Neurophysiol 103: 801–816

    Article  PubMed  Google Scholar 

  86. Ito S, Stuphorn V, Brown JW, Schall JD (2003) Performance monitoring by the anterior cingulate cortex during saccade countermanding. Science 302: 120–122

    Article  PubMed  CAS  Google Scholar 

  87. Pare M, Hanes DP (2003) Controlled movement processing: superior colliculus activity associated with countermanded saccades. J Neurosci 23: 6480–6489

    PubMed  CAS  Google Scholar 

  88. Logan GD, Cowan WB, Davis KA (1984) On the ability to inhibit simple and choice reaction time responses: a model and a method. J Exp Psychol Hum Percept Perform 10: 276

    Article  PubMed  CAS  Google Scholar 

  89. Munoz DP, Everling S (2004) Look away: the anti-saccade task and the voluntary control of eye movement. Nat Rev Neurosci 5: 218–228

    Article  PubMed  CAS  Google Scholar 

  90. Amador N, Schlag-Rey M, Schlag J (1998) Primate antisaccades. I. Behavioral characteristics. J Neurophysiol 80: 1775–1786

    CAS  Google Scholar 

  91. Skinner BF (1938) The Behavior of Organisms. Appleton-Century-Crofts, New York

    Google Scholar 

  92. Fuchs AF, Robinson DA (1966) A method for measuring horizontal and vertical eye movement chronically in the monkey. J Appl Physiol 21: 1068

    PubMed  CAS  Google Scholar 

  93. Stanton GB, Goldberg ME, Bruce CJ (1988) Frontal eye field efferents in the macaque monkey: II. Topography of terminal fields in midbrain and pons. J Comp Neurol 271: 493

    Google Scholar 

  94. Robinson DA (1972) Eye movements evoked by collicular stimulation in the alert monkey. Vision Res 12: 1795–1808

    Article  PubMed  CAS  Google Scholar 

  95. Andersen RA, Asanuma C, Essick G, Siegel RM (1990) Corticocortical connections of anatomically and physiologically defined subdivisions within the inferior parietal lobule. J Comp Neurol 296: 65

    Article  PubMed  CAS  Google Scholar 

  96. Ranck JB, Jr. (1975) Which elements are excited in electrical stimulation of mammalian central nervous system: a review. Brain Res 98: 417–440

    Article  PubMed  Google Scholar 

  97. Towe AL, Harding GW (1970) Extracellular microelectrode sampling bias. Exp Neurol 29: 366–381

    Article  PubMed  CAS  Google Scholar 

  98. Humphrey DR, Corrie WS (1978) Properties of pyramidal tract neuron system within a functionally defined subregion of primate motor cortex. J Neurophysiol 41: 216–243

    PubMed  CAS  Google Scholar 

  99. Jones EG, Wise SP (1977) Size, laminar and columnar distribution of efferent cells in the sensory-motor cortex of monkeys. J Comp Neurol 175: 391–438

    Article  PubMed  CAS  Google Scholar 

  100. Connors BW, Gutnick MJ (1990) Intrinsic firing patterns of diverse neocortical neurons. Trends Neurosci 13: 99–104

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This research was supported by a grant from the Canadian Institutes of Health Research (CIHR).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kevin Johnston .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this protocol

Cite this protocol

Johnston, K., Everling, S. (2011). An Approach to Understanding the Neural Circuitry of Saccade Control in the Cerebral Cortex Using Antidromic Identification in the Awake Behaving Macaque Monkey Model. In: Lane, E., Dunnett, S. (eds) Animal Models of Movement Disorders. Neuromethods, vol 62. Humana Press. https://doi.org/10.1007/978-1-61779-301-1_9

Download citation

  • DOI: https://doi.org/10.1007/978-1-61779-301-1_9

  • Published:

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-61779-300-4

  • Online ISBN: 978-1-61779-301-1

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics