Experimental Brain Research

, Volume 160, Issue 1, pp 89–106 | Cite as

Ocular oscillations generated by coupling of brainstem excitatory and inhibitory saccadic burst neurons

  • Stefano Ramat
  • R. John Leigh
  • David S. Zee
  • Lance M. Optican
Research Article

Abstract

The human saccadic system is potentially unstable and may oscillate if the burst neurons, which generate saccades, are not inhibited by omnipause neurons. A previous study showed that combined saccade vergence movements can evoke oscillations in normal subjects. We set out to determine: 1) whether similar oscillations can be recorded during other paradigms associated with inhibition of omnipause neurons; 2) whether lesions of the fastigial nuclei disrupt such oscillations; and 3) whether such oscillations can be reproduced using a model based on the coupling of excitatory and inhibitory burst neurons. We recorded saccadic oscillations during vergence movements, combined saccade-vergence movements, vertical saccades, pure vergence and blinks in three normal subjects, and in a patient with saccadic hypermetria due to a surgical lesion affecting both fastigial nuclei. During combined saccade-vergence, normal subjects and the cerebellar patient developed small-amplitude (0.1–0.5°), high-frequency (27–35 Hz), conjugate horizontal saccadic oscillations. Oscillations of a similar amplitude and frequency occurred during blinks, pure vergence and vertical saccades. One normal subject could generate saccadic oscillations voluntarily (~0.7° amplitude, 25 Hz) during sustained convergence. Previous models proposed that high-frequency eye oscillations produced by the saccadic system (saccadic oscillations), occur because of a delay in a negative feedback loop around high-gain, excitatory burst neurons in the brainstem. The feedback included the cerebellar fastigial nuclei. We propose another model that accounts for saccadic oscillations based on 1) coupling of excitatory and inhibitory burst neurons in the brainstem and 2) the hypothesis that burst neurons show post-inhibitory rebound discharge. When omnipause neurons are inhibited (as during saccades, saccade-vergence movements and blinks), this new model simulates oscillations with amplitudes and frequencies comparable to those in normal human subjects. The finding of saccadic oscillations in the cerebellar patient is compatible with the new model but not with the recent models including the fastigial nuclei in the classic negative-feedback loop model. Our model proposes a novel mechanism for generating oscillations in the oculomotor system and perhaps in other motor systems too.

Keywords

Brainstem Burst neurons Postinhibitory rebound discharge Saccadic mechanism Saccadic oscillations 

Notes

Acknowledgements

Supported by USPHS grant EY06717, the Office of Research and Development, Medical Research Service, Department of Veterans Affairs, and the Evenor Armington Fund (to R.J. Leigh), USPHS grant EY01849 to D.S. Zee. David Linden provided helpful discussion. Dr. Stefano Ramat was supported by the Robert M. and Annetta J. Coffelt Endowment for PSP research. The authors are grateful to Jeffrey Somers for assistance with experiments.

References

  1. Aizenman CD, Linden DJ (1999) Regulation of the rebound depolarization and spontaneous firing patterns of deep nuclear neurons in slices of rat cerebellum. J Neurophysiol 82:1697–1709PubMedGoogle Scholar
  2. Ashe J, Hain TC, Zee DS, Schatz NJ (1991) Microsaccadic flutter. Brain 114:461–472PubMedGoogle Scholar
  3. Bergamin O, Zee DS, Roberts DC, Landau K, Lasker AG, Straumann D (2001) Three-dimensional Hess screen test with binocular dual search coils in a three-field magnetic system. Invest Ophthalmol Vis Sci 42:660–667PubMedGoogle Scholar
  4. Bhidayasiri R, Somers JT, Kim JI, Ramat S, Nayak S, Bokil HS, Leigh RJ (2001) Ocular oscillations induced by shifts of the direction and depth of visual fixation. Ann Neurol 49:24–28CrossRefPubMedGoogle Scholar
  5. Busettini C, Mays LE (2003) Pontine omnipause activity during conjugate and disconjugate eye movements in macaques. J Neurophysiol 90:3838–3853PubMedGoogle Scholar
  6. Büttner-Ennever JA, Büttner U (1992) Neuroanatomy of the ocular motor pathways. Baillieres Clin Neurol 1:263–287PubMedGoogle Scholar
  7. Büttner-Ennever JA, Cohen B, Pause M, Fries W (1988) Raphe nucleus of the pons containing omnipause neurons of the oculomotor system in the monkey, and its homologue in man. J Comp Neurol 267:307–321PubMedGoogle Scholar
  8. Chun KS, Robinson DA (1978) A model of quick phase generation in the vestibuloocular reflex. Biol Cybern 28:209–221PubMedGoogle Scholar
  9. Collewijn H, van der SJ, Steinman RM (1985) Human eye movements associated with blinks and prolonged eyelid closure. J Neurophysiol 54:11–27PubMedGoogle Scholar
  10. Dean P (1995) Modelling the role of the cerebellar fastigial nuclei in producing accurate saccades: the importance of burst timing. Neuroscience 68:1059–1077CrossRefPubMedGoogle Scholar
  11. Duvernoy HM (1995) The human brain stem and the cerebellum. Springer, New YorkGoogle Scholar
  12. Efron B, Tibshirani RJ (1993) An introduction to the bootstrap. Chapman and Hall, New YorkGoogle Scholar
  13. Enderle JD, Engelken EJ (1995) Simulation of oculomotor post-inhibitory rebound burst firing using a Hodgkin-Huxley model of a neuron. Biomed Sci Instrum 31:53–58PubMedGoogle Scholar
  14. Evinger C, Kaneko CR, Fuchs AF (1982) Activity of omnipause neurons in alert cats during saccadic eye movements and visual stimuli. J Neurophysiol 47:827–844PubMedGoogle Scholar
  15. Hain TC, Zee DS, Mordes M (1986) Blink-induced saccadic oscillations. Ann Neurol 19:299–301PubMedGoogle Scholar
  16. Hepp K, Henn V, Vilis T, Cohen B (1989) Brainstem regions related to saccade generation. Rev Oculomot Res 3:105–212PubMedGoogle Scholar
  17. Horn AK, Büttner-Ennever JA, Suzuki Y, Henn V (1995) Histological identification of premotor neurons for horizontal saccades in monkey and man by parvalbumin immunostaining. J Comp Neurol 359:350–363PubMedGoogle Scholar
  18. Hotson JR (1984) Convergence-initiated voluntary flutter: a normal intrinsic capability in man. Brain Res 294:299–304CrossRefPubMedGoogle Scholar
  19. Huguenard JR (1998) Low-voltage-activated (T-type) calcium-channel genes identified. Trends Neurosci 21:451–452CrossRefPubMedGoogle Scholar
  20. Huntsman MM, Porcello DM, Homanics GE, DeLorey TM, Huguenard JR (1999) Reciprocal inhibitory connections and network synchrony in the mammalian thalamus. Science 283:541–543CrossRefPubMedGoogle Scholar
  21. Jacobsen RB, Ulrich D, Huguenard JR (2001) GABA(B) and NMDA receptors contribute to spindle-like oscillations in rat thalamus in vitro. J Neurophysiol 86:1365–1375PubMedGoogle Scholar
  22. Jurgens R, Becker W, Kornhuber HH (1981) Natural and drug-induced variations of velocity and duration of human saccadic eye movements: evidence for a control of the neural pulse generator by local feedback. Biol Cybern 39:87–96PubMedGoogle Scholar
  23. Keller EL (1974) Participation of medial pontine reticular formation in eye movement generation in monkey. J Neurophysiol 37:316–332PubMedGoogle Scholar
  24. Lefèvre P, Quaia C, Optican LM (1998) Distributed model of control of saccades by superior colliculus and cerebellum. Neural Netw 11:1175–1190CrossRefPubMedGoogle Scholar
  25. Leigh RJ, Zee DS (1999) The neurology of eye movements. Oxford University PressGoogle Scholar
  26. Mays LE, Gamlin PD (1995) Neuronal circuitry controlling the near response. Curr Opin Neurobiol 5:763–768CrossRefPubMedGoogle Scholar
  27. Mays LE, Morrisse DW (1995) Electrical stimulation of the pontine omnipause area inhibits eye blink. J Am Optom Assoc 66:419–422PubMedGoogle Scholar
  28. Optican LM, Quaia C (2002) Distributed model of collicular and cerebellar function during saccades. Ann N Y Acad Sci 956:164–177PubMedGoogle Scholar
  29. Perez-Reyes E (2003) Molecular physiology of low-voltage-activated t-type calcium channels. Physiol Rev 83:117–161PubMedGoogle Scholar
  30. Quaia C, Optican LM (1997) Model with distributed vectorial premotor bursters accounts for the component stretching of oblique saccades. J Neurophysiol 78:1120–1134PubMedGoogle Scholar
  31. Quaia C, Lefevre P, Optican LM (1999) Model of the control of saccades by superior colliculus and cerebellum. J Neurophysiol 82:999–1018PubMedGoogle Scholar
  32. Ramat S, Somers JT, Das VE, Leigh RJ (1999) Conjugate ocular oscillations during shifts of the direction and depth of visual fixation. Invest Ophthalmol Vis Sci 40:1681–1686PubMedGoogle Scholar
  33. Roberts A, Tunstall MJ (1990) Mutual re-excitation with post-inhibitory rebound: a simulation study on the mechanisms for locomotor rhythm generation in the spinal cord of xenopus embryos. Eur J Neurosci 2:11–23PubMedGoogle Scholar
  34. Robinson DA (1964) The mechanics of human saccadic eye movement. J Physiol (London) 174:245–264Google Scholar
  35. Robinson DA (1975) Oculomotor control signals. In: Lennerstrand G, Bach-y-Rita P (eds) Basic mechanisms of ocular motility and their clinical implications. Pergamon Press, Oxford, pp 337–374Google Scholar
  36. Robinson FR, Fuchs AF (2001) The role of the cerebellum in voluntary eye movements. Annu Rev Neurosci 24:981–1004CrossRefPubMedGoogle Scholar
  37. Robinson DA, Keller EL (1972) The behavior of eye movement motoneurons in the alert monkey. Bibl Ophthalmol 82:7–16PubMedGoogle Scholar
  38. Robinson FR, Straube A, Fuchs AF (1993) Role of the caudal fastigial nucleus in saccade generation. II. Effects of muscimol inactivation. J Neurophysiol 70:1741–1758PubMedGoogle Scholar
  39. Rottach KG, Das VE, Wohlgemuth W, Zivotofsky AZ, Leigh RJ (1998) Properties of horizontal saccades accompanied by blinks. J Neurophysiol 79:2895–2902PubMedGoogle Scholar
  40. Scudder CA (1988) A new local feedback model of the saccadic burst generator. J Neurophysiol 59:1455–1475PubMedGoogle Scholar
  41. Scudder CA, Fuchs AF, Langer TP (1988) Characteristics and functional identification of saccadic inhibitory burst neurons in the alert monkey. J Neurophysiol 59:1430–1454PubMedGoogle Scholar
  42. Scudder CA, Kaneko CS, Fuchs AF (2002) The brainstem burst generator for saccadic eye movements. A modern synthesis. Exp Brain Res 142:439–462CrossRefPubMedGoogle Scholar
  43. Sekirnjak C, du Lac S (2002) Intrinsic firing dynamics of vestibular nucleus neurons. J Neurosci 22:2083–2095PubMedGoogle Scholar
  44. Shults WT, Stark L, Hoyt WF, Ochs AL (1977) Normal saccadic structure of voluntary nystagmus. Arch Ophthalmol 95:1399–1404PubMedGoogle Scholar
  45. Soetedjo R, Kaneko CR, Fuchs AF (2002) Evidence that the superior colliculus participates in the feedback control of saccadic eye movements. J Neurophysiol 87:679–695PubMedGoogle Scholar
  46. Sohal VS, Huntsman MM, Huguenard JR (2000) Reciprocal inhibitory connections regulate the spatiotemporal properties of intrathalamic oscillations. J Neurosci 20:1735–1745PubMedGoogle Scholar
  47. Sparks DL (2002) The brainstem control of saccadic eye movements. Nat Rev Neurosci 3:952–964CrossRefPubMedGoogle Scholar
  48. Strassman A, Highstein SM, McCrea RA (1986a) Anatomy and physiology of saccadic burst neurons in the alert squirrel monkey. I. Excitatory burst neurons. J Comp Neurol 249:337–357PubMedGoogle Scholar
  49. Strassman A, Highstein SM, McCrea RA (1986b) Anatomy and physiology of saccadic burst neurons in the alert squirrel monkey. II. Inhibitory burst neurons. J Comp Neurol 249:358–380PubMedGoogle Scholar
  50. Sylvestre PA, Galiana HL, Cullen KE (2002) Conjugate and vergence oscillations during saccades and gaze shifts: implications for integrated control of binocular movement. J Neurophysiol 87:257–272PubMedGoogle Scholar
  51. Van Gisbergen JA, Robinson DA, Gielen S (1981) A quantitative analysis of generation of saccadic eye movements by burst neurons. J Neurophysiol 45:417–442PubMedGoogle Scholar
  52. Wong AM, Musallam S, Tomlinson RD, Shannon P, Sharpe JA (2001) Opsoclonus in three dimensions: oculographic, neuropathologic and modelling correlates. J Neurol Sci 189:71–81CrossRefPubMedGoogle Scholar
  53. Yee RD, Spiegel PH, Yamada T, Abel LA, Suzuki DA, Zee DS (1994) Voluntary saccadic oscillations, resembling ocular flutter and opsoclonus. J Neuroophthalmol 14:95–101PubMedGoogle Scholar
  54. Zee DS, Hain TC (1992) Clinical implications of otolith-ocular reflexes. Am J Otol 13:152–157PubMedGoogle Scholar
  55. Zee DS, Robinson DA (1979) A hypothetical explanation of saccadic oscillations. Ann Neurol 5:405–414PubMedGoogle Scholar
  56. Zee DS, Fitzgibbon EJ, Optican LM (1992) Saccade-vergence interactions in humans. J Neurophysiol 68:1624–1641PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Stefano Ramat
    • 1
  • R. John Leigh
    • 2
  • David S. Zee
    • 1
  • Lance M. Optican
    • 3
  1. 1.Department of NeurologyThe Johns Hopkins UniversityBaltimoreUSA
  2. 2.Department of Neurology, Veterans Affairs Medical Center and University HospitalsCase Western Reserve UniversityClevelandUSA
  3. 3.Laboratory of Sensorimotor ResearchNational Eye Institute, NIHBethesdaUSA

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