Skip to main content
Log in

Membrane channel properties of premotor excitatory burst neurons may underlie saccade slowing after lesions of omnipause neurons

  • Published:
Journal of Computational Neuroscience Aims and scope Submit manuscript

Abstract

Chemical lesions of the brain stem region containing glycinergic omnipause neurons (OPNs) cause saccade slowing with no change in latency. To explore the mechanisms responsible for this deficit, simulation studies were performed with a conductance-based model of premotor excitatory burst neurons (EBNs) that incorporated multiple membrane channels, including the T-type calcium channel. The peak speed of a normal saccade was determined by the T- and NMDA currents in EBNs after the OPNs shut off. After OPN lesions, the model made slow saccades, because the EBN activity was lower than normal due to a reduced T-current (caused by the loss of hyperpolarization), and a reduced NMDA current (caused by a reduced glycine concentration around the receptors). Thus, we propose that two biophysical mechanisms are responsible for saccade slowing after OPN lesions: reduced T-current and reduced NMDA current, both of which are caused by the loss of glycine from OPNs.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Ahmadi S, Muth-Selbach U, Lauterbach A, Lipfert P, Neuhuber WL, Zeilhofer HU (2003) Facilitation of spinal NMDA receptor currents by spillover of synaptically released glycine. Science 300: 2094–2097.

    Article  CAS  PubMed  Google Scholar 

  • Arai K, Das S, Keller EL, Aiyoshi E (1999) A distributed model of the saccade system: simulations of temporally perturbed saccades using position and velocity feedback. Neural. Networks 12: 1359–1375.

    Article  PubMed  Google Scholar 

  • Büttner-Ennever JA, Büttner U (1988) The reticular formation. In: Büttner-Ennever JA, ed. Neuroanatomy of the Oculomotor System. Elsevier, Amsterdam, pp. 119–176.

  • 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: 307–321.

    Article  PubMed  Google Scholar 

  • Chimoto S, Iwamoto Y, Shimazu H, Yoshida K (1996) Monosynaptic activation of medium-lead burst neurons from the superior colliculus in the alert cat. J. Neurophysiol. 75: 2658–2661.

    CAS  PubMed  Google Scholar 

  • Cohen B, Henn V (1972) Unit activity in the pontine reticular formation associated with eye movements. Brain Res. 46: 403–410.

    Article  CAS  PubMed  Google Scholar 

  • Dean P (1995) Modelling the role of the cerebellar fastigial nuclei in producing accurate saccades: The importance of burst timing. Neurosci. 68: 1059–1077.

    Article  CAS  Google Scholar 

  • Destexhe A, Contreras D, Sejnowski TJ, Steriade M (1994) A model of spindle rhythmicity in the isolated thalamic reticular nucleus. J. Neurophysiol. 72: 803–818.

    CAS  PubMed  Google Scholar 

  • Enderle JD (2002) Neural control of saccades. Prog. Brain Res. 140: 21–49.

    Article  PubMed  Google Scholar 

  • 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: 53–58.

    CAS  PubMed  Google Scholar 

  • Harty TP, Manis PB (1998) Kinetic analysis of glycine receptor currents in ventral cochlear nucleus. J. Neurophysiol. 79: 1891–1901.

    CAS  PubMed  Google Scholar 

  • Hepp K, Henn V, Vilis T, Cohen B (1989) Brainstem regions related to saccade generation. In: Wurtz RH, Goldberg ME, eds. The Neurobiology of Saccadic Eye Movements, Reviews of Oculomotor Research, Vol. III. Elsevier, Amsterdam, pp. 105–212.

  • Hikosaka O, Igusa Y, Imai H (1980) Inhibitory connections of nystagmus-related reticular burst neurons with neurons in the abducens, prepositus hypoglossi and vestibular nuclei in the cat. Exp. Brain. Res. 39: 301–311.

    CAS  PubMed  Google Scholar 

  • Horn AK, Büttner-Ennever JA, Wahle P, Reichenberger I (1994) Neurotransmitter profile of saccadic omnipause neurons in nucleus raphe interpositus. J. Neurosci. 14: 2032–2046.

    CAS  PubMed  Google Scholar 

  • Huang L, Keyser BM, Tagmose TM, Hansen JB, Taylor JT, Zhuang H, Zhang M, Ragsdale DS, Li M (2004) NNC 55-0396 [(1S,2S)-2-(2-(N-[(3-benzimidazol-2-yl)propyl]-N-methylamino)ethyl)-6-fluo ro-1,2,3,4-tetrahydro-1-isopropyl-2-naphtyl cyclopropanecarboxylate dihydrochloride]: a new selective inhibitor of T-type calcium channels. J. Pharmacol. Exp. Ther. 309: 193–199.

    Article  CAS  PubMed  Google Scholar 

  • Huguenard JR (1996) Low-threshold calcium currents in central nervous system neurons. Annu. Rev. Physiol. 58: 329–348.

    Article  CAS  PubMed  Google Scholar 

  • Huguenard JR (1998) Low-voltage-activated (T-type) calcium-channel genes identified. Trends Neurosci. 21: 451–452.

    Article  CAS  PubMed  Google Scholar 

  • Huguenard JR, McCormick DA (1992) Simulation of the currents involved in rhythmic oscillations in thalamic relay neurons. J. Neurophysiol. 68: 1373–1383.

    CAS  PubMed  Google Scholar 

  • Jahr CE, Stevens CF (1987) Glutamate activates multiple single channel conductances in hippocampal neurons. Nature 325: 522–525.

    Article  CAS  PubMed  Google Scholar 

  • Johnson JW, Ascher P (1987) Glycine potentiates the NMDA response in cultured mouse brain neurons. Nature 325: 529–531.

    Article  CAS  PubMed  Google Scholar 

  • Johnson JW, Ascher P (1992) Equilibrium and kinetic study of glycine action on the N-methyl-D-aspartate receptor in cultured mouse brain neurons. J. Physiol. 455: 339–365.

    CAS  PubMed  Google Scholar 

  • Jürgens 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: 87–96.

    Article  PubMed  Google Scholar 

  • Kaneko CR (1989) Hypothetical explanation of selective saccadic palsy caused by pontine lesion. Neurology. 39: 994–995.

    CAS  PubMed  Google Scholar 

  • Kaneko CR (1996) Effect of ibotenic acid lesions of the omnipause neurons on saccadic eye movements in rhesus macaques. J. Neurophysiol. 75: 2229–2242.

    CAS  PubMed  Google Scholar 

  • Keller EL (1974) Participation of medial pontine reticular formation in eye movement generation in monkey. J. Neurophysiol. 37: 316–332.

    CAS  PubMed  Google Scholar 

  • Keller EL, Edelman JA (1994) Use of interrupted saccade paradigm to study spatial and temporal dynamics of saccadic burst cells in superior colliculus in monkey. J. Neurophysiol. 72: 2754–2770.

    CAS  PubMed  Google Scholar 

  • Keller EL, McPeek RM, Salz T (2000) Evidence against direct connections to PPRF EBNs from SC in the monkey. J. Neurophysiol. 84: 1303–1313.

    CAS  PubMed  Google Scholar 

  • Koch C (1999) Biophysics of Computation. Oxford University Press, Inc., New York, NY.

  • Langer TP, Kaneko CR (1990) Brainstem afferents to the oculomotor omnipause neurons in monkey. J. Comp. Neurol. 295: 413–427.

    Article  CAS  PubMed  Google Scholar 

  • Lefèvre P, Quaia C, Optican LM (1998) Distributed model of control of sacades by superior colliculus and cerebellum. Neural. Networks 11: 1175–1190.

    Article  PubMed  Google Scholar 

  • Leigh RJ, Zee DS (1999) The Neurology of Eye Movements. Oxford, New York.

  • Luschei ES, Fuchs AF (1972) Activity of brain stem neurons during eye movements of alert monkeys. J. Neurophysiol. 35: 445–461.

    CAS  PubMed  Google Scholar 

  • McBain CJ, Mayer ML (1994) N-methyl-D-aspartic acid receptor structure and function. Physiol. Rev. 74: 723–760.

    CAS  PubMed  Google Scholar 

  • Miura K, Optican LM (2003) Membrane properties of medium-lead burst neurons may contribute to dynamical properties of saccades. Proceedings of the 1st International IEEE EMBS Conference on Neural Engineering: 20–23.

  • Miura K, Optican LM (2006 in press) Saccade Slowing After Lesions of Omnipause Neurons Explained By Two Hypothetical Membrane Properties of Premotor Burst Neurons. In: Akay M, ed. Neural Engineering Brain Imaging And Brain-Computer Interface. John Wiley and Sons.

  • Noda H, Sugita S, Ikeda Y (1990) Afferent and efferent connections of the oculomotor region of the fastigial nucleus in the macaque monkey. J. Comp. Neurol. 302: 330–348.

    Article  CAS  PubMed  Google Scholar 

  • Optican LM (2005) Sensorimotor transformation for visually guided saccades. Ann. NY Acad. Sci. 1039: 132–148.

    Article  PubMed  Google Scholar 

  • Optican LM, Quaia C (2002) Distributed model of collicular and cerebellar function during saccades. Ann NY Acad. Sci. 956: 164–177.

    Article  PubMed  Google Scholar 

  • Optican LM, Quaia Q (2001) From sensory space to motor commands: Lessons from saccades. Proc. IEEE EMBC Conf. 1: 820–823.

    Google Scholar 

  • Perez-Reyes E (2003) Molecular physiology of low-voltage-activated t-type calcium channels. Physiol. Rev. 83: 117–161.

    CAS  PubMed  Google Scholar 

  • Quaia C, Lefèvre P, Optican LM (1999) Model of the control of saccades by superior colliculus and cerebellum. J. Neurophysiol. 82: 999–1018.

    CAS  PubMed  Google Scholar 

  • Quaia C, Optican LM (1997) Model with distributed vectorial premotor bursters accounts for the component stretching of oblique saccades. J. Neurophysiol. 78: 1120–1134.

    CAS  PubMed  Google Scholar 

  • Robinson DA (1973) Models of the saccadic eye movement control system. Kybernetik 14: 71–83.

    Article  CAS  PubMed  Google Scholar 

  • 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. 337–374.

  • Scudder CA (1988) A new local feedback model of the saccadic burst generator. J. Neurophysiol. 59: 1455–1475.

    CAS  PubMed  Google Scholar 

  • Scudder CA, Fuchs AF, Langer TP (1988) Characteristics and functional identification of saccadic inhibitory burst neurons in the alert monkey. J. Neurophysiol. 59: 1430–1454.

    CAS  PubMed  Google Scholar 

  • Scudder CA, Kaneko CS, Fuchs AF (2002) The brainstem burst generator for saccadic eye movements: a modern synthesis. Exp. Brain. Res. 142: 439–462.

    Article  PubMed  Google Scholar 

  • Smith MR, Nelson AB, Du Lac S (2002) Regulation of firing response gain by calcium-dependent mechanisms in vestibular nucleus neurons. J. Neurophysiol. 87: 2031–2042.

    PubMed  Google Scholar 

  • Soetedjo R, Kaneko CR, Fuchs AF (2002) Evidence that the superior colliculus participates in the feedback control of saccadic eye movements. J. Neurophysiol. 87: 679–695.

    PubMed  Google Scholar 

  • Sparks DL (2002) The brainstem control of saccadic eye movements. Nat. Rev. Neurosci. 3: 952–964.

    Article  CAS  PubMed  Google Scholar 

  • Spencer RF, Wenthold RJ, Baker R (1989) Evidence for glycine as an inhibitory neurotransmitter of vestibular, reticular, and prepositus hypoglossi neurons that project to the cat abducens nucleus. J. Neurosci. 9: 2718–2736.

    CAS  PubMed  Google Scholar 

  • Strassman A, Evinger C, McCrea RA, Baker RG, Highstein SM (1987) Anatomy and physiology of intracellularly labelled omnipause neurons in the cat and squirrel monkey. Exp. Brain Res. 67: 436–440.

    Article  CAS  PubMed  Google Scholar 

  • 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: 337–357.

    Article  CAS  PubMed  Google Scholar 

  • 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: 358–380.

    Article  CAS  PubMed  Google Scholar 

  • Tegnér J, Compte A, Wang XJ (2002) The dynamical stability of reverberatory neural circuits. Biol. Cybern. 87: 471–481.

    Article  PubMed  Google Scholar 

  • Thomson AM, Walker VE, Flynn DM (1989) Glycine enhances NMDA-receptor mediated synaptic potentials in neocortical slices. Nature 338: 422–424.

    Article  CAS  PubMed  Google Scholar 

  • Traub RD, Wong RK, Miles R, Michelson H (1991) A model of a CA3 hippocampal pyramidal neuron incorporating voltage-clamp data on intrinsic conductances. J. Neurophysiol. 66: 635–650.

    CAS  PubMed  Google Scholar 

  • Turecek R, Trussell LO (2001) Presynaptic glycine receptors enhance transmitter release at a mammalian central synapse. Nature 411: 587–590.

    Article  CAS  PubMed  Google Scholar 

  • Van Gisbergen JA, Robinson DA, Gielen S (1981) A quantitative analysis of generation of saccadic eye movements by burst neurons. J. Neurophysiol. 45: 417–442.

    CAS  PubMed  Google Scholar 

  • Yoshida K, Iwamoto Y, Chimoto S, Shimazu H (1999) Saccade-related inhibitory input to pontine omnipause neurons: an intracellular study in alert cats. J. Neurophysiol. 82: 1198–1208.

    CAS  PubMed  Google Scholar 

  • Zee DS, Optican LM, Cook JD, Robinson DA, Engel WK (1976) Slow saccades in spinocerebellar degeneration. Arch. Neurol. 33: 243–251.

    CAS  PubMed  Google Scholar 

  • Zee DS, Robinson DA (1979) A hypothetical explanation of saccadic oscillations. Ann. Neurol. 5: 405–414.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Lance M. Optican.

Additional information

Action Editor: Karen Sigvardt

Rights and permissions

Reprints and permissions

About this article

Cite this article

Miura, K., Optican, L.M. Membrane channel properties of premotor excitatory burst neurons may underlie saccade slowing after lesions of omnipause neurons. J Comput Neurosci 20, 25–41 (2006). https://doi.org/10.1007/s10827-006-4258-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10827-006-4258-y

Keywords

Navigation