 |
||||
|
||||
|
||||
|
||||
Previous Article | Next Article
The Journal of Neuroscience, June 15, 2000, 20(12):4423-4434
Prolonged Synaptic Currents and Glutamate Spillover at the Parallel Fiber to Stellate Cell Synapse
Adam G. Carter and Wade G. Regehr Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115
Although neurons often fire in bursts, most of what is known about glutamate signaling and postsynaptic receptor activation is based on experiments using single stimuli. Here we examine the activation of ionotropic glutamate receptors by bursts at the parallel fiber to stellate cell synapse. We show that brief stimulus trains generate prolonged AMPA receptor (AMPAR)- and NMDA receptor (NMDAR)-mediated EPSCs recorded in whole-cell voltage clamp. These EPSCs contrast with the rapid AMPAR-mediated EPSC evoked by a single stimulus. The prolonged AMPAR-mediated EPSC is promoted by high-frequency and high-intensity trains and can persist for hundreds of milliseconds. This EPSC is also increased by L-trans-2,4-PDC, an inhibitor of glutamate transporters, suggesting that these transporters usually limit the synaptic response to trains. These prolonged EPSCs reflect both receptor properties and a long-lasting glutamate signal. In addition, several experiments demonstrate that glutamate spillover can contribute to receptor activation. First, imaging stimulus-evoked changes in presynaptic calcium establishes that distinct parallel fiber bands can be activated. Second, activation of parallel fibers that do not directly synapse onto a given stellate cell can evoke indirect AMPAR- and NMDAR-mediated EPSCs in that cell. Third, experiments using the use-dependent NMDAR blocker MK-801 show that these indirect EPSCs reflect glutamate spillover in response to trains. Together, these findings indicate that stimulus trains can generate a sustained and widespread glutamate signal that can in turn evoke large and prolonged EPSCs mediated by ionotropic glutamate receptors. These synaptic properties may have important functional consequences for stellate cell firing.
Key words: granule cell; parallel fiber; stellate cell; cerebellum; AMPA receptor; NMDA receptor; glutamate; transporter; spillover
Copyright © 2000 Society for Neuroscience 0270-6474/00/20124423-12$05.00/0
This article has been cited by other articles:
J. S. Dittman and J. M. Kaplan
Behavioral Impact of Neurotransmitter-Activated G-Protein-Coupled Receptors: Muscarinic and GABAB Receptors Regulate Caenorhabditis elegans Locomotion
J. Neurosci., July 9, 2008; 28(28): 7104 - 7112.
[Abstract] [Full Text] [PDF]
S. Astori and G. Kohr
Sustained granule cell activity disinhibits juvenile mouse cerebellar stellate cells through presynaptic mechanisms
J. Physiol., January 15, 2008; 586(2): 575 - 592.
[Abstract] [Full Text] [PDF]
J. Szabadics, G. Tamas, and I. Soltesz
Different transmitter transients underlie presynaptic cell type specificity of GABAA,slow and GABAA,fast
PNAS, September 11, 2007; 104(37): 14831 - 14836.
[Abstract] [Full Text] [PDF]
L. Sun and S. June Liu
Activation of extrasynaptic NMDA receptors induces a PKC-dependent switch in AMPA receptor subtypes in mouse cerebellar stellate cells
J. Physiol., September 1, 2007; 583(2): 537 - 553.
[Abstract] [Full Text] [PDF]
D. A. DiGregorio, J. S. Rothman, T. A. Nielsen, and R. A. Silver
Desensitization Properties of AMPA Receptors at the Cerebellar Mossy Fiber Granule Cell Synapse
J. Neurosci., August 1, 2007; 27(31): 8344 - 8357.
[Abstract] [Full Text] [PDF]
S. J. Liu
Biphasic Modulation of GABA Release From Stellate Cells by Glutamatergic Receptor Subtypes
J Neurophysiol, July 1, 2007; 98(1): 550 - 556.
[Abstract] [Full Text] [PDF]
J. J. Crowley, A. G. Carter, and W. G. Regehr
Fast Vesicle Replenishment and Rapid Recovery from Desensitization at a Single Synaptic Release Site
J. Neurosci., May 16, 2007; 27(20): 5448 - 5460.
[Abstract] [Full Text] [PDF]
R. Piet and C. E. Jahr
Glutamatergic and Purinergic Receptor-Mediated Calcium Transients in Bergmann Glial Cells
J. Neurosci., April 11, 2007; 27(15): 4027 - 4035.
[Abstract] [Full Text] [PDF]
D.-l. Qiu and T. Knopfel
An NMDA Receptor/Nitric Oxide Cascade in Presynaptic Parallel Fiber-Purkinje Neuron Long-Term Potentiation
J. Neurosci., March 28, 2007; 27(13): 3408 - 3415.
[Abstract] [Full Text] [PDF]
M. Beierlein and W. G. Regehr
Local Interneurons Regulate Synaptic Strength by Retrograde Release of Endocannabinoids
J. Neurosci., September 27, 2006; 26(39): 9935 - 9943.
[Abstract] [Full Text] [PDF]
S. J. Liu and P. Lachamp
The Activation of Excitatory Glutamate Receptors Evokes a Long-Lasting Increase in the Release of GABA from Cerebellar Stellate Cells
J. Neurosci., September 6, 2006; 26(36): 9332 - 9339.
[Abstract] [Full Text] [PDF]
A. Rancillac, J. Rossier, M. Guille, X.-K. Tong, H. Geoffroy, C. Amatore, S. Arbault, E. Hamel, and B. Cauli
Glutamatergic Control of Microvascular Tone by Distinct GABA Neurons in the Cerebellum.
J. Neurosci., June 28, 2006; 26(26): 6997 - 7006.
[Abstract] [Full Text] [PDF]
Y. Takayasu, M. Iino, K. Shimamoto, K. Tanaka, and S. Ozawa
Glial glutamate transporters maintain one-to-one relationship at the climbing fiber-Purkinje cell synapse by preventing glutamate spillover.
J. Neurosci., June 14, 2006; 26(24): 6563 - 6572.
[Abstract] [Full Text] [PDF]
J. M. Christie and G. L. Westbrook
Lateral excitation within the olfactory bulb.
J. Neurosci., February 22, 2006; 26(8): 2269 - 2277.
[Abstract] [Full Text] [PDF]
S.-i. Sekizawa and A. C. Bonham
Group I Metabotropic Glutamate Receptors on Second-Order Baroreceptor Neurons Are Tonically Activated and Induce a Na+-Ca2+ Exchange Current
J Neurophysiol, February 1, 2006; 95(2): 882 - 892.
[Abstract] [Full Text] [PDF]
T. Nieus, E. Sola, J. Mapelli, E. Saftenku, P. Rossi, and E. D'Angelo
LTP Regulates Burst Initiation and Frequency at Mossy Fiber-Granule Cell Synapses of Rat Cerebellum: Experimental Observations and Theoretical Predictions
J Neurophysiol, February 1, 2006; 95(2): 686 - 699.
[Abstract] [Full Text] [PDF]
A. Scimemi, S. Schorge, D. M. Kullmann, and M. C. Walker
Epileptogenesis Is Associated With Enhanced Glutamatergic Transmission in the Perforant Path
J Neurophysiol, February 1, 2006; 95(2): 1213 - 1220.
[Abstract] [Full Text] [PDF]
J. C. Holt, J.-T. Xue, A. M. Brichta, and J. M. Goldberg
Transmission Between Type II Hair Cells and Bouton Afferents in the Turtle Posterior Crista
J Neurophysiol, January 1, 2006; 95(1): 428 - 452.
[Abstract] [Full Text] [PDF]
J. H. Shin and D. J. Linden
An NMDA Receptor/Nitric Oxide Cascade Is Involved in Cerebellar LTD But Is Not Localized to the Parallel Fiber Terminal
J Neurophysiol, December 1, 2005; 94(6): 4281 - 4289.
[Abstract] [Full Text] [PDF]
Y. Takayasu, M. Iino, W. Kakegawa, H. Maeno, K. Watase, K. Wada, D. Yanagihara, T. Miyazaki, O. Komine, M. Watanabe, et al.
Differential Roles of Glial and Neuronal Glutamate Transporters in Purkinje Cell Synapses
J. Neurosci., September 21, 2005; 25(38): 8788 - 8793.
[Abstract] [Full Text] [PDF]
M. R. Sullivan, A. Nimmerjahn, D. V. Sarkisov, F. Helmchen, and S. S.-H. Wang
In Vivo Calcium Imaging of Circuit Activity in Cerebellar Cortex
J Neurophysiol, August 1, 2005; 94(2): 1636 - 1644.
[Abstract] [Full Text] [PDF]
D. A. Rusakov, F. Saitow, K. P. Lehre, and S. Konishi
Modulation of Presynaptic Ca2+ Entry by AMPA Receptors at Individual GABAergic Synapses in the Cerebellum
J. Neurosci., May 18, 2005; 25(20): 4930 - 4940.
[Abstract] [Full Text] [PDF]
J. R. Pugh and I. M. Raman
GABAA Receptor Kinetics in the Cerebellar Nuclei: Evidence for Detection of Transmitter from Distant Release Sites
Biophys. J., March 1, 2005; 88(3): 1740 - 1754.
[Abstract] [Full Text] [PDF]
J.-i. Tanaka, M. Matsuzaki, E. Tarusawa, A. Momiyama, E. Molnar, H. Kasai, and R. Shigemoto
Number and Density of AMPA Receptors in Single Synapses in Immature Cerebellum
J. Neurosci., January 26, 2005; 25(4): 799 - 807.
[Abstract] [Full Text] [PDF]
R. Lim, P. Hoang, and A. J. Berger
Blockade of Glycine Transporter-1 (GLYT-1) Potentiates NMDA Receptor-Mediated Synaptic Transmission in Hypoglossal Motorneurons
J Neurophysiol, October 1, 2004; 92(4): 2530 - 2537.
[Abstract] [Full Text] [PDF]
M. H. Karakossian and T. S. Otis
Excitation of Cerebellar Interneurons by Group I Metabotropic Glutamate Receptors
J Neurophysiol, September 1, 2004; 92(3): 1558 - 1565.
[Abstract] [Full Text] [PDF]
A. Scimemi, A. Fine, D. M. Kullmann, and D. A. Rusakov
NR2B-Containing Receptors Mediate Cross Talk among Hippocampal Synapses
J. Neurosci., May 19, 2004; 24(20): 4767 - 4777.
[Abstract] [Full Text] [PDF]
Y. H. Huang, S. R. Sinha, K. Tanaka, J. D. Rothstein, and D. E. Bergles
Astrocyte Glutamate Transporters Regulate Metabotropic Glutamate Receptor-Mediated Excitation of Hippocampal Interneurons
J. Neurosci., May 12, 2004; 24(19): 4551 - 4559.
[Abstract] [Full Text] [PDF]
A. Rancillac and F. Crepel
Synapses between parallel fibres and stellate cells express long-term changes in synaptic efficacy in rat cerebellum
J. Physiol., February 1, 2004; 554(3): 707 - 720.
[Abstract] [Full Text] [PDF]
L. Cathala, S. Brickley, S. Cull-Candy, and M. Farrant
Maturation of EPSCs and Intrinsic Membrane Properties Enhances Precision at a Cerebellar Synapse
J. Neurosci., July 9, 2003; 23(14): 6074 - 6085.
[Abstract] [Full Text] [PDF]
L. S. Overstreet and G. L. Westbrook
Synapse Density Regulates Independence at Unitary Inhibitory Synapses
J. Neurosci., April 1, 2003; 23(7): 2618 - 2626.
[Abstract] [Full Text] [PDF]
G. C. Mathews and J. S. Diamond
Neuronal Glutamate Uptake Contributes to GABA Synthesis and Inhibitory Synaptic Strength
J. Neurosci., March 15, 2003; 23(6): 2040 - 2048.
[Abstract] [Full Text] [PDF]
K. P. Lehre and D. A. Rusakov
Asymmetry of Glia near Central Synapses Favors Presynaptically Directed Glutamate Escape
Biophys. J., July 1, 2002; 83(1): 125 - 134.
[Abstract] [Full Text] [PDF]
B. A. Clark and S. G. Cull-Candy
Activity-Dependent Recruitment of Extrasynaptic NMDA Receptor Activation at an AMPA Receptor-Only Synapse
J. Neurosci., June 1, 2002; 22(11): 4428 - 4436.
[Abstract] [Full Text] [PDF]
W. Reichelt and T. Knopfel
Glutamate Uptake Controls Expression of a Slow Postsynaptic Current Mediated by mGluRs in Cerebellar Purkinje Cells
J Neurophysiol, April 1, 2002; 87(4): 1974 - 1980.
[Abstract] [Full Text] [PDF]
S. Chen and J. S. Diamond
Synaptically Released Glutamate Activates Extrasynaptic NMDA Receptors on Cells in the Ganglion Cell Layer of Rat Retina
J. Neurosci., March 15, 2002; 22(6): 2165 - 2173.
[Abstract] [Full Text] [PDF]
E. Neher and T. Sakaba
Estimating Transmitter Release Rates from Postsynaptic Current Fluctuations
J. Neurosci., December 15, 2001; 21(24): 9638 - 9654.
[Abstract] [Full Text] [PDF]
J. S. Diamond
Neuronal Glutamate Transporters Limit Activation of NMDA Receptors by Neurotransmitter Spillover on CA1 Pyramidal Cells
J. Neurosci., November 1, 2001; 21(21): 8328 - 8338.
[Abstract] [Full Text] [PDF]
B. Barbour
An Evaluation of Synapse Independence
J. Neurosci., October 15, 2001; 21(20): 7969 - 7984.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|