Location of Repository

Differences in Transmission Properties and Susceptibility to Long-Term Depression Reveal Functional Specialization of Ascending Axon and Parallel Fiber Synapses to Purkinje Cells

By R. E. Sims and Nicholas A. Hartell


An understanding of the patterns of mossy fiber transmission to Purkinje cells, via granule cell axons, is fundamental to models of cerebellar cortical signaling and processing. Early theories assumed that mossy fiber input is widely disseminated across the cerebellar cortex along beams of parallel fibers, which spread for several millimeters across the cerebellar cortex. Direct evidence for this has, however, proved controversial, leading to the development of an alternative hypothesis that mossy fiber inputs to the cerebral cortex are in fact vertically organized such that the ascending segment of the granule axon carries a greater synaptic weight than the parallel fiber segment. Here, we report that ascending axon synapses are selectively resistant to cerebellar long-term depression and that they release transmitter with higher mean release probabilities and mean quantal amplitudes than parallel fiber synapses. This novel specialization of synapses formed by different segments of the same axon not only explains the reported patterns of granule cell→ Purkinje cell transmission across the cerebellar cortex but also reveals an additional level of functionality and complexity of cerebellar processing. Consequently, ascending axon synapses represent a new element of cortical signal processing that should be distinguished from parallel fiber synapses in future experimental and theoretical studies of cerebellar function.This work was supported by the Biotechnology and Biological Sciences Research Council and the Royal Society

Topics: cerebellum, long-term depression, synaptic, transmission, granule cell, Purkinje cell
Publisher: Society for Neuroscience
Year: 2005
DOI identifier: 10.1523/JNEUROSCI.0073-05.2005
OAI identifier: oai:lra.le.ac.uk:2381/1789

Suggested articles



  1. (1990). 2,3-Dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline: a neuroprotectant for cerebral ischemia. doi
  2. (1957). A quantitative study of the Purkinje cell dendritic branchlets and their relationship to afferent fibres.
  3. (1969). A theory of cerebellar cortex. doi
  4. (1991). Applicability of the coefficient of variation method for analyzing synaptic plasticity. doi
  5. (1999). Ascending granule cell axon: an important component of cerebellar cortical circuitry. doi
  6. (2001). Cerebellar long-term depression: characterisation, signal transduction, and functional roles. Physiol Rev 81:1143–1195.
  7. (2001). Compartmental models of rat cerebellar Purkinje cells based on simultaneous somatic and dendritic patch-clamp recordings. doi
  8. (1996). Contributions of calcium-dependent and calcium-independent mechanisms to presynaptic inhibition at a cerebellar synapse.
  9. (1997). Delta-glutamate receptors are differentially distributed at parallel and climbing fiber synapses on Purkinje cells. doi
  10. (2000). Disruption of AMPA receptor GluR2 clusters following long-term depression induction in cerebellar Purkinje neurons. doi
  11. (1983). Effects of extracellular potassium concentration on the excitability of the parallel fibres of the rat cerebellum. doi
  12. (1990). Excitatory synaptic currents in Purkinje cells. doi
  13. (2000). Expression of cerebellar long-term depression requires postsynaptic clathrin-mediated endocytosis. doi
  14. (2000). Facilitation, augmentation andpotentiation at central synapses.
  15. (2002). General and variable features of varicosity spacing along unmyelinated axons in the hippocampus and cerebellum. doi
  16. (1982). General discussion: radial connectivity in the cerebellar cortex. A novel view regarding the functional organization of the molecular layer. In: The cerebellum: new vistas (Palay SL, Chan-Palay V, eds), pp 189–194. doi
  17. (2005). Hartell • Functional Differences between Granule Cell3Purkinje Cell Synapses
  18. (1997). Heterogeneous release properties of visualized individual hippocampal synapses. doi
  19. (1972). Integration by Purkyne cells of mossy and climbing fiber inputs from cutaneous mechanoreceptors. Exp Brain Res 15:498–520. doi
  20. (2004). Integration of quanta in cerebellar granule cells during sensory processing. doi
  21. (1967). Interpretation of the potential fields generated in the cerebellar cortex by a mossy fibre volley. Exp Brain Res 3:58–80. doi
  22. (1998). Konnerth A doi
  23. (1998). Local calcium signalling by inositol-1,4,5-trisphosphate in Purkinje cell dendrites.
  24. (1998). Locus of frequencydependent depression identified with multiple-probability fluctuation analysis at rat climbing fibre-Purkinje cell synapses. doi
  25. (2002). Modulatory effects of parallel fiber and molecular layer interneuron synaptic activity on Purkinje cell responses to ascending segment input: a modeling study.
  26. (2001). Morphological correlates of functionally defined synaptic vesicle populations.
  27. (1994). Morphology of parallel fibres in the cerebellar cortex of the rat: an experimental light and electron microscopic study with biocytin. doi
  28. (2003). No parallel fiber volleys in the cerebellar cortex: evidence from cross-correlation analysis between Purkinje cells in a computer model and in recordings from anesthetized rats.
  29. (1988). Number of parallel fiber synapses on an individual Purkinje cell in the cerebellum of the rat. doi
  30. (2002). Parallel fiber plasticity. doi
  31. (1998). Patches of synchronized activity in the cerebellar cortex evoked bymossy-fiber stimulation: questioning the role of parallel fibers. doi
  32. (2002). Properties of unitary granule cell3Purkinje cell synapses in adult rat cerebellar slices.
  33. (1991). Quantitative studies on the mammalian cerebellum. Prog Neurobiol 36:437–463. doi
  34. (2001). Random response fluctuations lead to spurious paired-pulse facilitation.
  35. (1989). Short-term synaptic plasticity. doi
  36. (1994). Signal transmission in the parallel fiber-Purkinje cell system visualized by highresolution imaging. doi
  37. (1997). Spatial distribution of field potential profiles in the cat cerebellar cortex evoked by peripheral and central inputs. doi
  38. (1992). Spread of synaptic activity along parallel fibres in cat cerebellar anterior lobe. Exp Brain Res 88:615–622. doi
  39. (1974). The cerebellar cortex. Cytology and organization. doi
  40. (1983). The length of cerebellar parallel fibers in chicken and rhesus monkey. doi
  41. (2002). The molecular organization of cerebellar long-term depression. doi
  42. (1992). The time course of glutamate in the synaptic cleft. doi
  43. (2001). Three-dimensional comparison of ultrastructural characteristics at depressing and facilitating synapses onto cerebellar Purkinje cells.
  44. (2000). Unveiling synaptic plasticity: a new graphical and analytical approach. doi
  45. (1998). Variations in the tangential distribution of postsynaptic glutamate receptors in Purkinje cell parallel and climbing fiber synapses during development.Neuropharmacology 37:1321–1334. doi

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.