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. 1996 Dec 1;497(Pt 2):531–537. doi: 10.1113/jphysiol.1996.sp021786

Glutamate as a candidate retrograde messenger at interneurone-Purkinje cell synapses of rat cerebellum.

M Glitsch 1, I Llano 1, A Marty 1
PMCID: PMC1161002  PMID: 8961193

Abstract

1. Depolarization-induced suppression of inhibition (DSI) is a form of synaptic plasticity which involves a retrograde messenger. We have performed experiments in Purkinje cells of rat cerebellar slices to determine the nature of this messenger. 2. DSI is mimicked by 2-(2,3-dicarboxycyclopropyl)-glycine (DCG-IV), a specific agonist of group II metabotropic glutamate receptors (mGluRs). 3. DSI is reduced if transmitter release is inhibited by saturating doses of DCG-IV. 4. Both DSI and DCG-IV-induced inhibition are inhibited by L-2-amino-3-phosphonopropionic acid (L-AP3), a drug which interferes with several subtypes of mGluRs. 5. DSI is reduced if synaptic activity is enhanced by application of forskolin. 6. We propose that glutamate or a glutamate-like substance is the retrograde messenger implicated in DSI, and that the inhibition resulting from presynaptic glutamate binding is mediated by a decrease in the presynaptic concentration of cAMP.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alger B. E., Pitler T. A. Retrograde signaling at GABAA-receptor synapses in the mammalian CNS. Trends Neurosci. 1995 Aug;18(8):333–340. doi: 10.1016/0166-2236(95)93923-l. [DOI] [PubMed] [Google Scholar]
  2. Attwell D., Barbour B., Szatkowski M. Nonvesicular release of neurotransmitter. Neuron. 1993 Sep;11(3):401–407. doi: 10.1016/0896-6273(93)90145-h. [DOI] [PubMed] [Google Scholar]
  3. Bliss T. V., Collingridge G. L. A synaptic model of memory: long-term potentiation in the hippocampus. Nature. 1993 Jan 7;361(6407):31–39. doi: 10.1038/361031a0. [DOI] [PubMed] [Google Scholar]
  4. Dan Y., Song H. J., Poo M. M. Evoked neuronal secretion of false transmitters. Neuron. 1994 Oct;13(4):909–917. doi: 10.1016/0896-6273(94)90256-9. [DOI] [PubMed] [Google Scholar]
  5. Fierro L., Llano I. High endogenous calcium buffering in Purkinje cells from rat cerebellar slices. J Physiol. 1996 Nov 1;496(Pt 3):617–625. doi: 10.1113/jphysiol.1996.sp021713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hayashi Y., Momiyama A., Takahashi T., Ohishi H., Ogawa-Meguro R., Shigemoto R., Mizuno N., Nakanishi S. Role of a metabotropic glutamate receptor in synaptic modulation in the accessory olfactory bulb. Nature. 1993 Dec 16;366(6456):687–690. doi: 10.1038/366687a0. [DOI] [PubMed] [Google Scholar]
  7. Llano I., Gerschenfeld H. M. Beta-adrenergic enhancement of inhibitory synaptic activity in rat cerebellar stellate and Purkinje cells. J Physiol. 1993 Aug;468:201–224. doi: 10.1113/jphysiol.1993.sp019767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Llano I., Leresche N., Marty A. Calcium entry increases the sensitivity of cerebellar Purkinje cells to applied GABA and decreases inhibitory synaptic currents. Neuron. 1991 Apr;6(4):565–574. doi: 10.1016/0896-6273(91)90059-9. [DOI] [PubMed] [Google Scholar]
  9. Llano I., Marty A. Presynaptic metabotropic glutamatergic regulation of inhibitory synapses in rat cerebellar slices. J Physiol. 1995 Jul 1;486(Pt 1):163–176. doi: 10.1113/jphysiol.1995.sp020800. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Marty A., Llano I. Modulation of inhibitory synapses in the mammalian brain. Curr Opin Neurobiol. 1995 Jun;5(3):335–341. doi: 10.1016/0959-4388(95)80046-8. [DOI] [PubMed] [Google Scholar]
  11. Ohishi H., Shigemoto R., Nakanishi S., Mizuno N. Distribution of the mRNA for a metabotropic glutamate receptor (mGluR3) in the rat brain: an in situ hybridization study. J Comp Neurol. 1993 Sep 8;335(2):252–266. doi: 10.1002/cne.903350209. [DOI] [PubMed] [Google Scholar]
  12. Parpura V., Basarsky T. A., Liu F., Jeftinija K., Jeftinija S., Haydon P. G. Glutamate-mediated astrocyte-neuron signalling. Nature. 1994 Jun 30;369(6483):744–747. doi: 10.1038/369744a0. [DOI] [PubMed] [Google Scholar]
  13. Pin J. P., Bockaert J. Get receptive to metabotropic glutamate receptors. Curr Opin Neurobiol. 1995 Jun;5(3):342–349. doi: 10.1016/0959-4388(95)80047-6. [DOI] [PubMed] [Google Scholar]
  14. Pitler T. A., Alger B. E. Depolarization-induced suppression of GABAergic inhibition in rat hippocampal pyramidal cells: G protein involvement in a presynaptic mechanism. Neuron. 1994 Dec;13(6):1447–1455. doi: 10.1016/0896-6273(94)90430-8. [DOI] [PubMed] [Google Scholar]
  15. Pitler T. A., Alger B. E. Postsynaptic spike firing reduces synaptic GABAA responses in hippocampal pyramidal cells. J Neurosci. 1992 Oct;12(10):4122–4132. doi: 10.1523/JNEUROSCI.12-10-04122.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Poncer J. C., Shinozaki H., Miles R. Dual modulation of synaptic inhibition by distinct metabotropic glutamate receptors in the rat hippocampus. J Physiol. 1995 May 15;485(Pt 1):121–134. doi: 10.1113/jphysiol.1995.sp020717. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Staub C., Vranesic I., Knöpfel T. Responses to Metabotropic Glutamate Receptor Activation in Cerebellar Purkinje Cells: Induction of an Inward Current. Eur J Neurosci. 1992;4(9):832–839. doi: 10.1111/j.1460-9568.1992.tb00193.x. [DOI] [PubMed] [Google Scholar]
  18. Vincent P., Armstrong C. M., Marty A. Inhibitory synaptic currents in rat cerebellar Purkinje cells: modulation by postsynaptic depolarization. J Physiol. 1992 Oct;456:453–471. doi: 10.1113/jphysiol.1992.sp019346. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Vincent P., Marty A. Neighboring cerebellar Purkinje cells communicate via retrograde inhibition of common presynaptic interneurons. Neuron. 1993 Nov;11(5):885–893. doi: 10.1016/0896-6273(93)90118-b. [DOI] [PubMed] [Google Scholar]

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