Mechanism and Kinetics of Heterosynaptic Depression at a Cerebellar Synapse

Overview

Journal J Neurosci

Specialty Neurology

Date 1997 Dec 31

PMID 9364051

Citations 52

Authors

J S Dittman

W G Regehr

Affiliations

Soon will be listed here.

Abstract

High levels of activity at a synapse can lead to spillover of neurotransmitter from the synaptic cleft. This extrasynaptic neurotransmitter can diffuse to neighboring synapses and modulate transmission via presynaptic receptors. We studied such modulation at the synapse between granule cells and Purkinje cells in rat cerebellar slices. Brief tetanic stimulation of granule cell parallel fibers activated inhibitory neurons, leading to a transient elevation of extracellular GABA, which in turn caused a short-lived heterosynaptic depression of the parallel fiber to Purkinje cell EPSC. Fluorometric calcium measurements revealed that this synaptic inhibition was associated with a decrease in presynaptic calcium influx. Heterosynaptic inhibition of synaptic currents and calcium influx was eliminated by antagonists of the GABAB receptor. The magnitude and time course of the depression of calcium influx were mimicked by the rapid release of an estimated 10 microM GABA using the technique of flash photolysis. We found that inhibition of presynaptic calcium influx peaked within 300 msec and decayed in <3 sec at 32 degrees C. These results indicate that presynaptic GABAB receptors can sense extrasynaptic GABA increases of several micromolar and that they rapidly regulate the release of neurotransmitter primarily by modulating voltage-gated calcium channels.

Citing Articles

Co-release of GABA and ACh from medial olivocochlear neurons fine tunes cochlear efferent inhibition.

Castagnola T, Castagna V, Kitcher S, Torres Cadenas L, Di Guilmi M, Gomez Casati M bioRxiv. 2024; .

PMID: 39185230 PMC: 11343139. DOI: 10.1101/2024.08.12.607644.

Emerging modes of regulation of neuromodulatory G protein-coupled receptors.

Gonzalez-Hernandez A, Munguba H, Levitz J Trends Neurosci. 2024; 47(8):635-650.

PMID: 38862331 PMC: 11324403. DOI: 10.1016/j.tins.2024.05.008.

Simple spike patterns and synaptic mechanisms encoding sensory and motor signals in Purkinje cells and the cerebellar nuclei.

Brown S, Medina-Pizarro M, Holla M, Vaaga C, Raman I Neuron. 2024; 112(11):1848-1861.e4.

PMID: 38492575 PMC: 11156563. DOI: 10.1016/j.neuron.2024.02.014.

Botulinum neurotoxin accurately separates tonic vs. phasic transmission and reveals heterosynaptic plasticity rules in .

Han Y, Chien C, Goel P, He K, Pinales C, Buser C Elife. 2022; 11.

PMID: 35993544 PMC: 9439677. DOI: 10.7554/eLife.77924.

Convergent, functionally independent signaling by mu and delta opioid receptors in hippocampal parvalbumin interneurons.

He X, Patel J, Weiss C, Ma X, Bloodgood B, Banghart M Elife. 2021; 10.

PMID: 34787079 PMC: 8716102. DOI: 10.7554/eLife.69746.

References

Wu L, Saggau P . Adenosine inhibits evoked synaptic transmission primarily by reducing presynaptic calcium influx in area CA1 of hippocampus. Neuron. 1994; 12(5):1139-48. DOI: 10.1016/0896-6273(94)90321-2. View

Starke K . Presynaptic receptors. Annu Rev Pharmacol Toxicol. 1981; 21:7-30. DOI: 10.1146/annurev.pa.21.040181.000255. View

Isaacson J, Solis J, Nicoll R . Local and diffuse synaptic actions of GABA in the hippocampus. Neuron. 1993; 10(2):165-75. DOI: 10.1016/0896-6273(93)90308-e. View

Regehr W, Tank D . Selective fura-2 loading of presynaptic terminals and nerve cell processes by local perfusion in mammalian brain slice. J Neurosci Methods. 1991; 37(2):111-9. DOI: 10.1016/0165-0270(91)90121-f. View

Zhou J, Shapiro M, Hille B . Speed of Ca2+ channel modulation by neurotransmitters in rat sympathetic neurons. J Neurophysiol. 1997; 77(4):2040-8. DOI: 10.1152/jn.1997.77.4.2040. View

Lerma J, Herranz A, Herreras O, Abraira V, Martin del Rio R . In vivo determination of extracellular concentration of amino acids in the rat hippocampus. A method based on brain dialysis and computerized analysis. Brain Res. 1986; 384(1):145-55. DOI: 10.1016/0006-8993(86)91230-8. View

Pfrieger F, Gottmann K, Lux H . Kinetics of GABAB receptor-mediated inhibition of calcium currents and excitatory synaptic transmission in hippocampal neurons in vitro. Neuron. 1994; 12(1):97-107. DOI: 10.1016/0896-6273(94)90155-4. View

Guyon A, Leresche N . Modulation by different GABAB receptor types of voltage-activated calcium currents in rat thalamocortical neurones. J Physiol. 1995; 485 ( Pt 1):29-42. PMC: 1157970. DOI: 10.1113/jphysiol.1995.sp020710. View

Scholz K, Miller R . GABAB receptor-mediated inhibition of Ca2+ currents and synaptic transmission in cultured rat hippocampal neurones. J Physiol. 1991; 444:669-86. PMC: 1179955. DOI: 10.1113/jphysiol.1991.sp018900. View

10.

Zucker R . Short-term synaptic plasticity. Annu Rev Neurosci. 1989; 12:13-31. DOI: 10.1146/annurev.ne.12.030189.000305. View

11.

Gage P . Activation and modulation of neuronal K+ channels by GABA. Trends Neurosci. 1992; 15(2):46-51. DOI: 10.1016/0166-2236(92)90025-4. View

12.

Bonanno G, Raiteri M . Multiple GABAB receptors. Trends Pharmacol Sci. 1993; 14(7):259-61. DOI: 10.1016/0165-6147(93)90124-3. View

13.

Olpe H, Karlsson G, Pozza M, Brugger F, Steinmann M, van Riezen H . CGP 35348: a centrally active blocker of GABAB receptors. Eur J Pharmacol. 1990; 187(1):27-38. DOI: 10.1016/0014-2999(90)90337-6. View

14.

Sahara Y, Westbrook G . Modulation of calcium currents by a metabotropic glutamate receptor involves fast and slow kinetic components in cultured hippocampal neurons. J Neurosci. 1993; 13(7):3041-50. PMC: 6576670. View

15.

Anwyl R . Modulation of vertebrate neuronal calcium channels by transmitters. Brain Res Brain Res Rev. 1991; 16(3):265-81. DOI: 10.1016/0165-0173(91)90010-6. View

16.

Kaupmann K, Huggel K, Heid J, Flor P, Bischoff S, Mickel S . Expression cloning of GABA(B) receptors uncovers similarity to metabotropic glutamate receptors. Nature. 1997; 386(6622):239-46. DOI: 10.1038/386239a0. View

17.

Davies C, Pozza M, Collingridge G . CGP 55845A: a potent antagonist of GABAB receptors in the CA1 region of rat hippocampus. Neuropharmacology. 1993; 32(10):1071-3. DOI: 10.1016/0028-3908(93)90073-c. View

18.

Jones S . Time course of receptor-channel coupling in frog sympathetic neurons. Biophys J. 1991; 60(2):502-7. PMC: 1260088. DOI: 10.1016/S0006-3495(91)82077-X. View

19.

Pekhletski R, Gerlai R, Overstreet L, Huang X, Agopyan N, Slater N . Impaired cerebellar synaptic plasticity and motor performance in mice lacking the mGluR4 subtype of metabotropic glutamate receptor. J Neurosci. 1996; 16(20):6364-73. PMC: 6578923. View

20.

Marr D . A theory of cerebellar cortex. J Physiol. 1969; 202(2):437-70. PMC: 1351491. DOI: 10.1113/jphysiol.1969.sp008820. View