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J Neurophysiol 87: 2624-2628, 2002;
0022-3077/02 $5.00
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The Journal of Neurophysiology Vol. 87 No. 5 May 2002, pp. 2624-2628
Copyright ©2002 by the American Physiological Society

RAPID COMMUNICATION

Selective Modulation of Tonic and Phasic Inhibitions in Dentate Gyrus Granule Cells

Zoltan Nusser1,2 and Istvan Mody1

 1Department of Neurology, UCLA School of Medicine, Los Angeles, California 90095-1769; and  2Laboratory of Cellular Neurophysiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, 1083 Budapest, Hungary

Nusser, Zoltan and Istvan Mody. Selective Modulation of Tonic and Phasic Inhibitions in Dentate Gyrus Granule Cells. J. Neurophysiol. 87: 2624-2628, 2002. In some nerve cells, activation of GABAA receptors by GABA results in phasic and tonic conductances. Transient activation of synaptic receptors generates phasic inhibition, whereas tonic inhibition originates from GABA acting on extrasynaptic receptors, like in cerebellar granule cells, where it is thought to result from the activation of extrasynaptic GABAA receptors with a specific subunit composition (alpha 6beta xdelta ). Here we show that in adult rat hippocampal slices, extracellular GABA levels are sufficiently high to generate a powerful tonic inhibition in delta  subunit-expressing dentate gyrus granule cells. In these cells, the mean tonic current is approximately four times larger than that produced by spontaneous synaptic currents occurring at a frequency of ~10 Hz. Antagonizing the GABA transporter GAT-1 with NO-711 (2.5 µM) selectively enhanced tonic inhibition by 330% without affecting the phasic component. In contrast, by prolonging the decay of inhibitory postsynaptic currents (IPSCs), the benzodiazepine agonist zolpidem (0.5 µM) augmented phasic inhibition by 66%, while leaving the mean tonic conductance unchanged. These results demonstrate that a tonic GABAA receptor-mediated conductance can be recorded from dentate gyrus granule cells of adult rats in in vitro slice preparations. Furthermore, we have identified distinct pharmacological tools to selectively modify tonic and phasic inhibitions, allowing future studies to investigate their specific roles in neuronal function.




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B. M. Stell, S. G. Brickley, C. Y. Tang, M. Farrant, and I. Mody
Neuroactive steroids reduce neuronal excitability by selectively enhancing tonic inhibition mediated by {delta} subunit-containing GABAA receptors
PNAS, November 25, 2003; 100(24): 14439 - 14444.
[Abstract] [Full Text] [PDF]

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 J. Neurosci.Home page
W. Wei, N. Zhang, Z. Peng, C. R. Houser, and I. Mody
Perisynaptic Localization of {delta} Subunit-Containing GABAA Receptors and Their Activation by GABA Spillover in the Mouse Dentate Gyrus
J. Neurosci., November 19, 2003; 23(33): 10650 - 10661.
[Abstract] [Full Text] [PDF]

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 J. Neurosci.Home page
D. Belelli and M. B. Herd
The Contraceptive Agent Provera Enhances GABAA Receptor-Mediated Inhibitory Neurotransmission in the Rat Hippocampus: Evidence for Endogenous Neurosteroids?
J. Neurosci., November 5, 2003; 23(31): 10013 - 10020.
[Abstract] [Full Text] [PDF]

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 J. Neurophysiol.Home page
K. Jensen, C.-S. Chiu, I. Sokolova, H. A. Lester, and I. Mody
GABA Transporter-1 (GAT1)-Deficient Mice: Differential Tonic Activation of GABAA Versus GABAB Receptors in the Hippocampus
J Neurophysiol, October 1, 2003; 90(4): 2690 - 2701.
[Abstract] [Full Text] [PDF]

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 J. Neurophysiol.Home page
G. B. Richerson and Y. Wu
Dynamic Equilibrium of Neurotransmitter Transporters: Not Just for Reuptake Anymore
J Neurophysiol, September 1, 2003; 90(3): 1363 - 1374.
[Abstract] [Full Text] [PDF]

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 J. Neurosci.Home page
Y. Iwai, M. Fagiolini, K. Obata, and T. K. Hensch
Rapid Critical Period Induction by Tonic Inhibition in Visual Cortex
J. Neurosci., July 30, 2003; 23(17): 6695 - 6702.
[Abstract] [Full Text] [PDF]

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 J. Neurophysiol.Home page
Y. Wu, W. Wang, and G. B. Richerson
Vigabatrin Induces Tonic Inhibition Via GABA Transporter Reversal Without Increasing Vesicular GABA Release
J Neurophysiol, April 1, 2003; 89(4): 2021 - 2034.
[Abstract] [Full Text] [PDF]

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 J. Neurosci.Home page
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]

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 J. Neurophysiol.Home page
F.-C. Hsu and S. S. Smith
Progesterone Withdrawal Reduces Paired-Pulse Inhibition in Rat Hippocampus: Dependence on GABAA Receptor alpha 4 Subunit Upregulation
J Neurophysiol, January 1, 2003; 89(1): 186 - 198.
[Abstract] [Full Text] [PDF]

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 Mol. Pharmacol.Home page
J. Y. T. Yeung, K. J. Canning, G. Zhu, P. Pennefather, J. F. MacDonald, and B. A. Orser
Tonically Activated GABAA Receptors in Hippocampal Neurons Are High-Affinity, Low-Conductance Sensors for Extracellular GABA
Mol. Pharmacol., January 1, 2003; 63(1): 2 - 8.
[Abstract] [Full Text] [PDF]


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