Skip to main content
SpringerLink
Log in

Excitatory afferent modulation of complex spike synchrony

  • Published:
The Cerebellum Aims and scope Submit manuscript

Abstract

Inferior olivary neurons receive extensive glutamatergic and GABAergic innervation. Yet, because of the membrane properties of olivary neurons these neurotransmitters can produce only small changes in the firing rates of these cells. Moreover, olivary neurons can generate spontaneous spike activity in the absence of excitatory glutamatergic input. These facts suggest that glutamate and GABA have additional roles within the olivocerebellar system beyond simply modulating single cell firing probability. Indeed, one of the characteristics of the olivocerebellar system is its ability to generate synchronous complex spike activity across populations of Purkinje cells. The pattern of synchronous activity changes rapidly, and is thought to reflect the momentary distribution of effective electrotonic coupling between olivary neurons as shaped by afferent input to the inferior olive. However, it also possible that synchronous olivocerebellar activity is the result of synchrony inherent in the afferent activity itself. The issue of the origin of complex spike synchrony, and the role of glutamatergic olivary afferents in modulating its distribution were recently studied using multiple electrode recordings from Purkinje cells. The results of these studies, reviewed here, demonstrate that synchronous complex spike activity occurs in the absence of glutamatergic (and GABAergic) input to the inferior olive, and therefore indicate that synchronization of complex spike activity primarily results from the electrotonic coupling of olivary neurons, rather than from synchronization present within their afferents. Instead of triggering synchronous discharges directly, the results suggest that the function of tonic excitatory activity is to modulate the effective coupling of spike activity between olivary neurons. Blocking glutamate within the inferior olive causes an enhancement of the normal banding pattern of complex spike synchrony, with higher synchrony among parasagittally aligned Purkinje cells and less synchrony between non-aligned cells. This is in contrast to the more uniform synchrony distribution that follows block of GABAergic olivary afferents. Thus, GABA and glutamate play critical, and complementary, roles in determining the patterns of synchronous complex spike activity that are likely central to the functioning of the olivocerebellar system.

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

Access this article

Log in via an institution

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

  1. Monaghan DT, Cotman CW. Distribution of N-methyl-Daspartate-sensitive L-[3H]glutamate-binding sites in rat brain. J Neurosci 1985: 5: 2909–2919.

    PubMed  CAS  Google Scholar 

  2. Petralia RS, Wenthold RJ. Light and electron immunocytochemical localization of AMPA-selective glutamate receptors in the rat brain. J Comp Neurol 1992; 318: 329–354.

    Article  PubMed  CAS  Google Scholar 

  3. Petralia RS, Yokotani N, Wenthold RJ. Light and electron microscope distribution of the NMDA receptor subunit NMDAR1 in the rat nervous system using a selective anti-peptide antibody. J Neurosci 1994; 14: 667–696.

    PubMed  CAS  Google Scholar 

  4. Petralia RS, Wang YX, Wenthold RJ. Histological and ultrastructural localization of the kainate receptor subunits, KA2 and GluR6/ 7, in the rat nervous system using selective antipeptide antibodies. J Comp Neurol 1994; 349: 85–110.

    Article  PubMed  CAS  Google Scholar 

  5. Ambalavanar R, Ludlow CL, Wenthold RJ, Tanaka Y, Damirjian M, Petralia RS. Glutamate receptor subunits in the nucleus of the tractus solitarius and other regions of the medulla oblongata in the cat. J Comp Neurol 1998; 402: 75–92.

    Article  PubMed  CAS  Google Scholar 

  6. Paarmann I, Frermann D, Keller BU, Hollmann M. Expression of 15 glutamate receptor subunits and various splice variants in tissue slices and single neurons of brainstem nuclei and potential function implications. J Neurochem 2000; 74: 1335–1345.

    Article  PubMed  CAS  Google Scholar 

  7. Jeneskog T. Termination in posterior and anterior cerebellum of a climbing fiber pathway activated from the nucleus of Darkschewitsch in the cat. Brain Res 1987; 412: 185–189.

    Article  PubMed  CAS  Google Scholar 

  8. De Zeeuw CI, Holstege JC, Ruigrok TJH, Voogd J. Ultrastructural study of the GABAergic, cerebellar, and mesodiencephalic innervation of the cat medial accessory olive: anterograde tracing combined with immunocytochemistry. J Comp Neurol 1989; 284: 12–35.

    Article  PubMed  Google Scholar 

  9. Onodera S, Hicks TP. Patterns of transmitter labelling and connectivity of the cat’s nucleus of Darkschewitsch: a wheat germ agglutinin-horseradish peroxidase and immunocytochemical study at light and electron microscopical levels. J Comp Neurol 1995; 361: 553–573.

    Article  PubMed  CAS  Google Scholar 

  10. Bishop GA, McCrea RA, Kitai ST. A horseradish peroxidase study of the cortico-olivary projection in the cat. Brain Res 1976; 116: 306–311.

    Article  PubMed  CAS  Google Scholar 

  11. Saint-Cyr JA. The projection from the motor cortex to the inferior olive in the cat. Neuroscience 1983; 10: 667–684.

    Article  PubMed  CAS  Google Scholar 

  12. Swenson RS, Castro AJ. The afferent connections of the inferior olivary complex in rats: a study using the retrograde transport of horseradish peroxidase. Am J Anat 1983; 166: 329–341.

    Article  PubMed  CAS  Google Scholar 

  13. Swenson RS, Castro AJ. The afferent connections of the inferior olivary complex in rats: an anterograde study using autoradiographic and axonal degeneration techniques. Neuroscience 1983; 8: 259–275.

    Article  PubMed  CAS  Google Scholar 

  14. Swenson RS, Sievert CF, Terreberry RR, Neafsey EJ, Castro AJ. Organization of cerebral cortico-olivary projections in the rat. Neurosci Res 1989; 7: 43–54.

    Article  PubMed  CAS  Google Scholar 

  15. DeFelipe J, Fariñas I. The pyramidal neuron of the cerebral cortex: morphological and chemical characteristics of the synaptic inputs. Prog Neurobiol 1992; 39: 563–607.

    Article  PubMed  CAS  Google Scholar 

  16. Valtschanoff JG, Weinberg RJ, Rustioni A. Amino acid immunoreactivity in corticospinal terminals. Exp Brain Res 1993; 93: 95–103.

    Article  PubMed  CAS  Google Scholar 

  17. Lang EJ. Organization of olivocerebellar activity in the absence of excitatory glutamatergic input. J Neurosci 2001; 21: 1663–1675.

    PubMed  CAS  Google Scholar 

  18. Duggan AW, Lodge D, Headley PM, Biscoe TJ. Effects of excitants on neurones and cerebellar-evoked field potentials in the inferior olivary complex of the rat. Brain Res 1973; 64: 397–401.

    Article  PubMed  CAS  Google Scholar 

  19. Llinás R, Yarom Y. Electrophysiology of mammalian inferior olivary neurones in vitro. Different types of voltage-dependent ionic conductances. J Physiol (Lond) 1981; 315: 549–567.

    Google Scholar 

  20. Llinás R, Yarom Y. Properties and distribution of ionic conductances generating electroresponsiveness of mammalian inferior olivary neurones in vitro. J Physiol (Lond) 1981; 315: 569–584.

    Google Scholar 

  21. Andersson G, Hesslow G. Activity of Purkinje cells and interpositus neurones during and after periods of high frequency climbing fibre activation in the cat. Exp Brain Res 1987; 67: 532–542.

    Google Scholar 

  22. Angaut P, Sotelo C. The dentato-olivary projection in the rat as a presumptive GABAergic link in the olivo-cerebello-olivary loop. An ultrastructural study. Neurosci Lett1987; 83: 227–231.

    Article  PubMed  CAS  Google Scholar 

  23. Fredette BJ, Mugnaini E. The GABAergic cerebello-olivary projection in the rat. Anat Embryol 1991; 184: 225–243.

    Article  PubMed  CAS  Google Scholar 

  24. Lang EJ, Sugihara I, Llinás R. GABAergic modulation of complex spike activity by the cerebellar nucleoolivary pathway in rat. J Neurophysiol 1996; 76: 255–275.

    PubMed  CAS  Google Scholar 

  25. Lang EJ. GABAergic and glutamatergic modulation of spontaneous and motor-cortex-evoked complex spike activity. J Neurophysiol 2002; 87: 1993–2008.

    PubMed  CAS  Google Scholar 

  26. Sasaki K, Bower JM, Llinás R. Multiple Purkinje cell recording in rodent cerebellar cortex. Eur J Neurosci 1989; 1: 572–586.

    Article  PubMed  Google Scholar 

  27. Sugihara I, Lang EJ, Llinás R. Uniform olivocerebellar conduction time underlies Purkinje cell complex spike synchronicity in the rat cerebellum. J Physiol (Lond) 1993; 470: 243–271.

    CAS  Google Scholar 

  28. Wylie DR, De Zeeuw CI, Simpson JI. Temporal relations of the complex spike activity of Purkinje cell pairs in the vestibulocerebellum of rabbits. J Neurosci 1995; 15: 2875–2887.

    PubMed  CAS  Google Scholar 

  29. Lang EJ, Sugihara I, Welsh JP, Llinás R. Patterns of spontaneous Purkinje cell complex spike activity in the awake rat. J Neurosci 1999; 19: 2728–2739.

    PubMed  CAS  Google Scholar 

  30. Llinás R, Baker R, Sotelo C. Electrotonic coupling between neurons in cat inferior olive. J Neurophysiol 1974; 37: 560–571.

    PubMed  Google Scholar 

  31. De Zeeuw CI, Hertzberg EL, Mugnaini E. The dendritic lamellar body: a new neuronal organeile putatively associated with dendrodendritic gap junctions. J Neurosci 1995; 15: 1587–1604.

    PubMed  Google Scholar 

  32. Condorelli DF, Parenti R, Spinella F, et al. Cloning of a new gap junction gene (Cx36) highly expressed in mammalian brain neurons. Eur J Neurosci 1998; 10: 1202–1208.

    Article  PubMed  CAS  Google Scholar 

  33. Belluardo N, Mudò G, Travato-Salinaro A, et al. Expression of connexin36 in the adult and developing rat brain. Brain Res 2000; 865: 121–138.

    Article  PubMed  CAS  Google Scholar 

  34. De Zeeuw CI, Koekkoek SKE, Wylie DRW, Simpson JI. Association between dendritic lamellar bodies and complex spike synchrony in the olivocerebellar system. J Neurophysiol 1997; 77: 1747–1758.

    PubMed  Google Scholar 

  35. Welsh JP, Lang EJ, Sugihara I, Llinás R. Dynamic organization of motor control within the olivocerebellar system. Nature 1995; 374: 453–457.

    Article  PubMed  CAS  Google Scholar 

  36. Sotelo C, Llinás R, Baker R. Structural study of inferior olivary nucleus of the cat: morphological correlates of electrotonic coupling. J Neurophysiol 1974; 37: 541–559.

    PubMed  CAS  Google Scholar 

  37. King JS. The synaptic cluster (glomerulus) in the inferior olivary nucleus. J Comp Neurol 1976; 165: 387–400.

    Article  PubMed  CAS  Google Scholar 

  38. Spira ME, Spray DC, Bennett MVL. Synaptic organization of expansion motoneurons of Navanax inermis. Brain Res 1980; 195: 241–269.

    Article  PubMed  CAS  Google Scholar 

  39. Llinás R. Eighteenth Bowditch lecture. Motor aspects of cerebellar control. Physiologist 1974; 17: 19–46.

    PubMed  Google Scholar 

  40. Nelson BJ, Mugnaini E. Origins of GABAergic inputs to the inferior olive. In: Strata P, editor. The Olivocerebellar System in Motor Control. Berlin, Springer-Verlag 1989.

    Google Scholar 

  41. Nelson BJ, Adams JC, Barmack NH, Mugnaini E. Comparative study of glutamate decarboxylase immunoreactive boutons in the mammalian inferior olive. J Comp Neurol 1989; 286: 514–539.

    Article  PubMed  CAS  Google Scholar 

  42. Sotelo C, Gotow T, Wassef M. Localization of glutamic-acid decarboxylase immunoreactive axon terminals in the inferior olive of the rat, with special emphasis on anatomical relations between GABAergic synapses and dendrodendritic gap junctions. J Comp Neurol 1986; 252: 32–50.

    Article  PubMed  CAS  Google Scholar 

  43. Llinás R, Sasaki K. The functional organization of the olivocerebellar system as examined by multiple Purkinje cell recordings. Eur J Neurosci 1989; 1: 587–602.

    Article  PubMed  Google Scholar 

  44. De Zeeuw CI, Ruigrok TJH, Holstege JC, Jansen HG, Voogd J. Intracellular labeling of neurons in the medial accessory olive of the cat: II. Ultrastructure dendritic spines and the GABAergic innervation. J Comp Neurol 1990; 300: 478–494.

    Article  PubMed  Google Scholar 

  45. De Zeeuw CI, Holstege JC, Ruigrok TJH, Voogd J. Mesodiencephalic and cerebellar terminals terminate upon the same dendritic spines in the glomeruli of the cat and rat inferior olive: an ultrastructural study using a combination of [H3] leucine and wheat germ agglutinin coupled horseradish peroxidase anterograde tracing. Neuroscience 1990; 34: 645–655.

    Article  PubMed  Google Scholar 

  46. De Zeeuw CI, Lang EJ, Sugihara I, Ruigrok TJH, Voogd J. Morphological correlates of bilateral synchrony in the rat cerebellar cortex. J Neurosci 1996; 16: 3412–3426.

    PubMed  Google Scholar 

  47. Sugihara I, Wu H-S, Shinoda Y. Morphology of single olivocerebellar axons labeled with biotinylated dextran amine in the rat. J Comp Neurol 1999; 414: 131–148.

    Article  PubMed  CAS  Google Scholar 

  48. Manor Y, Yarom Y, Chorev E, Devor A. To beat or not to beat: a decision taken at the network level. J Physiol (Paris) 2000; 94: 375–390.

    Article  CAS  Google Scholar 

  49. Gerstein GL, Kiang WY. An approach to the quantitative analysis of equations of electrophysiological data from single neurons. Biophys J 1960; 1: 15–28.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology & Neuroscience, New York University, School of Medicine, 550 First Avenue, 10016, New York, NY, USA

    Eric J. Lang

Authors
  1. Eric J. Lang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eric J. Lang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lang, E.J. Excitatory afferent modulation of complex spike synchrony. Cerebellum 2, 165–170 (2003). https://doi.org/10.1080/14734220310002542

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1080/14734220310002542

Keywords

Search

Navigation