Home LiteratureArticle Details
PMID: 1323125 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Brief dendritic calcium signals initiate long-lasting synaptic depression in cerebellar Purkinje cells.

Konnerth A, Dreessen J, Augustine GJ

Abstract

We have performed experiments designed to test the hypothesis that long-term depression (LTD) of excitatory synaptic transmission in the cerebellar cortex is caused by a rise in postsynaptic Ca concentration. These experiments combined measurements of synaptic efficacy, performed with the thin slice patch clamp technique, with fura-2 measurements of intracellular Ca concentration ([Ca]i) in single cerebellar Purkinje cells. Simultaneous activation of the climbing fiber and parallel fibers innervating single Purkinje cells caused a LTD of transmission of the parallel fiber-Purkinje cell excitatory synapse. This LTD was associated with large and transient rises in [Ca]i in the Purkinje cell and apparently was due to Ca entry through voltage-gated Ca channels in the Purkinje cell dendrites. The rise in [Ca]i produced by climbing fiber activity was necessary for LTD, because addition of the Ca chelator bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetate (BAPTA) to the interior of the Purkinje cell blocked LTD. Further, elevation of [Ca]i, produced by depolarizing pulses delivered in conjunction with parallel fiber activation, induced a depression of synaptic activity that closely resembled LTD in both time course and magnitude. Thus, a rise in [Ca]i appears to be sufficient to initiate LTD. From these results, we conclude that LTD of the parallel fiber-Purkinje cell synapse is initiated by a brief, climbing fiber-mediated rise in postsynaptic [Ca]i and that LTD is maintained by other, longer-lived processes that are triggered by the rise in postsynaptic [Ca]i.

MeSH Terms
Animals Calcium/metabolism Calcium Channels/drug effects,physiology Cerebellar Cortex/physiology Dendrites/physiology Egtazic Acid/analogs & derivatives,pharmacology In Vitro Techniques Kinetics Purkinje Cells/physiology Rats Synapses/physiology Synaptic Transmission Time Factors
Chemicals
Calcium Channels Egtazic Acid 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid Calcium
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Konnerth A
Max-Planck-Institut für biophysikalische Chemie, Göttingen, Germany.
Dreessen J
Augustine G J
References (41)
41 references, click to expand
  1. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches.
    Pflugers Arch. 1981 Aug;391(2):85-100 PMID: 6270629
  2. Activation of protein kinase C induces a long-term depression of glutamate sensitivity of cerebellar Purkinje cells. An in vitro study.
    Brain Res. 1988 Aug 23;458(2):397-401 PMID: 2905201
  3. Climbing fibre induced depression of both mossy fibre responsiveness and glutamate sensitivity of cerebellar Purkinje cells.
    J Physiol. 1982 Mar;324:113-34 PMID: 7097592
  4. Sequence and expression of a metabotropic glutamate receptor.
    Nature. 1991 Feb 28;349(6312):760-5 PMID: 1847995
  5. A thin slice preparation for patch clamp recordings from neurones of the mammalian central nervous system.
    Pflugers Arch. 1989 Sep;414(5):600-12 PMID: 2780225
  6. Presynaptic mechanism for long-term potentiation in the hippocampus.
    Nature. 1990 Aug 23;346(6286):724-9 PMID: 2167454
  7. Molecular biology of learning: modulation of transmitter release.
    Science. 1982 Oct 29;218(4571):433-43 PMID: 6289442
  8. Effects of postsynaptic depolarization in the induction of synaptic depression between a granule cell and a Purkinje cell in rat cerebellar culture.
    Neurosci Lett. 1990 Nov 13;119(2):145-7 PMID: 2280885
  9. Spatially resolved calcium dynamics of mammalian Purkinje cells in cerebellar slice.
    Science. 1988 Nov 4;242(4879):773-7 PMID: 2847315
  10. Excitatory amino acid receptors and synaptic plasticity.
    Trends Pharmacol Sci. 1990 Jul;11(7):290-6 PMID: 2167544
  11. Synaptic- and agonist-induced excitatory currents of Purkinje cells in rat cerebellar slices.
    J Physiol. 1991 Mar;434:183-213 PMID: 1673717
  12. Long-term depression.
    Annu Rev Neurosci. 1989;12:85-102 PMID: 2648961
  13. Climbing Fibre Responses in Olivo-cerebellar Slice Cultures. I. Microelectrode Recordings from Purkinje Cells.
    Eur J Neurosci. 1990;2(8):726-732 PMID: 12106291
  14. Hippocampal synaptic plasticity and NMDA receptors: a role in information storage?
    Philos Trans R Soc Lond B Biol Sci. 1990 Aug 29;329(1253):187-204 PMID: 1978364
  15. Quisqualate receptors are specifically involved in cerebellar synaptic plasticity.
    Nature. 1987 Jan 15-21;325(6101):276-9 PMID: 2880297
  16. Isolated mammalian brain in vitro: new technique for analysis of electrical activity of neuronal circuit function.
    Fed Proc. 1981 Jun;40(8):2240-5 PMID: 7238908
  17. Protein kinases, nitric oxide and long-term depression of synapses in the cerebellum.
    Neuroreport. 1990 Oct;1(2):133-6 PMID: 2129866
  18. Electrophysiological properties of in vitro Purkinje cell dendrites in mammalian cerebellar slices.
    J Physiol. 1980 Aug;305:197-213 PMID: 7441553
  19. Digital imaging of free calcium changes and of spatial gradients in growing processes in single, mammalian central nervous system cells.
    Proc Natl Acad Sci U S A. 1986 Aug;83(16):6179-83 PMID: 3461482
  20. Calcium channel.
    Annu Rev Neurosci. 1981;4:69-125 PMID: 6261668
  21. Long-term depression of parallel fibre synapses following stimulation of climbing fibres.
    Brain Res. 1985 Sep 9;342(2):357-60 PMID: 4041837
  22. Synaptic control of excitability in turtle cerebellar Purkinje cells.
    J Physiol. 1989 Feb;409:157-70 PMID: 2585289
  23. Prolonged depolarization elicited in Purkinje cell dendrites by climbing fibre impulses in the cat.
    J Physiol. 1981 Sep;318:207-21 PMID: 7320889
  24. A new generation of Ca2+ indicators with greatly improved fluorescence properties.
    J Biol Chem. 1985 Mar 25;260(6):3440-50 PMID: 3838314
  25. Synaptic currents in cerebellar Purkinje cells.
    Proc Natl Acad Sci U S A. 1990 Apr;87(7):2662-5 PMID: 1969639
  26. The neurobiology of learning and memory.
    Science. 1986 Aug 29;233(4767):941-7 PMID: 3738519
  27. Quantal components of the end-plate potential.
    J Physiol. 1954 Jun 28;124(3):560-73 PMID: 13175199
  28. Cytosolic Ca2+ gradients triggering unidirectional fluid secretion from exocrine pancreas.
    Nature. 1990 Dec 20-27;348(6303):735-8 PMID: 1701852
  29. Calcium gradients and buffers in bovine chromaffin cells.
    J Physiol. 1992 May;450:273-301 PMID: 1331424
  30. New calcium indicators and buffers with high selectivity against magnesium and protons: design, synthesis, and properties of prototype structures.
    Biochemistry. 1980 May 27;19(11):2396-404 PMID: 6770893
  31. Intradendritic release of calcium induced by glutamate in cerebellar Purkinje cells.
    Neuron. 1991 Oct;7(4):577-83 PMID: 1681831
  32. Calcium is an intracellular mediator of the climbing fiber in induction of cerebellar long-term depression.
    Proc Natl Acad Sci U S A. 1990 May;87(9):3383-5 PMID: 2159149
  33. Induction of long-term potentiation at hippocampal mossy-fiber synapses follows a Hebbian rule.
    J Neurophysiol. 1990 Sep;64(3):948-60 PMID: 2230936
  34. Inositolphospholipid-linked glutamate receptors mediate cerebellar parallel-fiber-Purkinje-cell synaptic transmission.
    Proc Natl Acad Sci U S A. 1989 Jun;86(11):4316-20 PMID: 2542969
  35. Messengers mediating long-term desensitization in cerebellar Purkinje cells.
    Neuroreport. 1990 Oct;1(2):129-32 PMID: 1966603
  36. Synaptic modification of parallel fibre-Purkinje cell transmission in in vitro guinea-pig cerebellar slices.
    J Physiol. 1987 Dec;394:463-80 PMID: 2832595
  37. A long-term depression of AMPA currents in cultured cerebellar Purkinje neurons.
    Neuron. 1991 Jul;7(1):81-9 PMID: 1676895
  38. Participation of postsynaptic PKC in cerebellar long-term depression in culture.
    Science. 1991 Dec 13;254(5038):1656-9 PMID: 1721243
  39. Mapping calcium transients in the dendrites of Purkinje cells from the guinea-pig cerebellum in vitro.
    J Physiol. 1987 Aug;389:319-36 PMID: 3681730
  40. Presynaptic enhancement shown by whole-cell recordings of long-term potentiation in hippocampal slices.
    Nature. 1990 Jul 12;346(6280):177-80 PMID: 2164158
  41. Pairing of pre- and postsynaptic activities in cerebellar Purkinje cells induces long-term changes in synaptic efficacy in vitro.
    J Physiol. 1991 Jan;432:123-41 PMID: 1886056
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1992-08-01
Pages
7051-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC49643
Subset
IM
Grants
NINDS NIH HHS · NS 21624 · United States
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com