Multiple modes of GABAergic inhibition of rat cerebellar granule cells

David J. Rossi, Martine Hamann, David Attwell

Research output: Contribution to journalArticle

187 Citations (Scopus)

Abstract

Cerebellar granule cells are inhibited phasically by GABA released synaptically from Golgi cells, but are inhibited more powerfully by tonic activity of high affinity α6 subunit-containing GABAA receptors. During development the tonic activity is generated by the accumulation of GABA released by action potentials, but in the adult the tonic activity is independent of action potentials. Here we show that in adult rats the tonic activation of GABAA receptors is produced by non-vesicular transmitter release and is reduced by the activity of GAT-1 and GAT-3 GABA transporters, demonstrating that alterations of GABA uptake will modulate information flow through granule cells. Acetylcholine (ACh) evokes a large Ca2+-dependent but action potential-independent release of GABA, which activates α6 subunit-containing GABAA receptors. These data show that three separate modes of transmitter release can activate GABAA receptors in adult cerebellar granule cells: action potential-evoked exocytotic GABA release, non-vesicular release, and ACh-evoked Ca2+-dependent release independent of action potentials. The relative magnitudes of the inhibitory charge transfers generated by action potential-evoked release (during high frequency stimulation of the mossy fibres), tonic inhibition and superfused ACh are 1:3:12, indicating that tonic and ACh-mediated inhibition may play a major role in regulating granule cell firing.

Original languageEnglish (US)
Pages (from-to)97-110
Number of pages14
JournalJournal of Physiology
Volume548
Issue number1
DOIs
StatePublished - Apr 1 2003

Fingerprint

gamma-Aminobutyric Acid
Action Potentials
GABA-A Receptors
Acetylcholine
GABA Plasma Membrane Transport Proteins

ASJC Scopus subject areas

  • Physiology

Cite this

Multiple modes of GABAergic inhibition of rat cerebellar granule cells. / Rossi, David J.; Hamann, Martine; Attwell, David.

In: Journal of Physiology, Vol. 548, No. 1, 01.04.2003, p. 97-110.

Research output: Contribution to journalArticle

Rossi, David J. ; Hamann, Martine ; Attwell, David. / Multiple modes of GABAergic inhibition of rat cerebellar granule cells. In: Journal of Physiology. 2003 ; Vol. 548, No. 1. pp. 97-110.
@article{3302765bc8424006847764918a3ba46b,
title = "Multiple modes of GABAergic inhibition of rat cerebellar granule cells",
abstract = "Cerebellar granule cells are inhibited phasically by GABA released synaptically from Golgi cells, but are inhibited more powerfully by tonic activity of high affinity α6 subunit-containing GABAA receptors. During development the tonic activity is generated by the accumulation of GABA released by action potentials, but in the adult the tonic activity is independent of action potentials. Here we show that in adult rats the tonic activation of GABAA receptors is produced by non-vesicular transmitter release and is reduced by the activity of GAT-1 and GAT-3 GABA transporters, demonstrating that alterations of GABA uptake will modulate information flow through granule cells. Acetylcholine (ACh) evokes a large Ca2+-dependent but action potential-independent release of GABA, which activates α6 subunit-containing GABAA receptors. These data show that three separate modes of transmitter release can activate GABAA receptors in adult cerebellar granule cells: action potential-evoked exocytotic GABA release, non-vesicular release, and ACh-evoked Ca2+-dependent release independent of action potentials. The relative magnitudes of the inhibitory charge transfers generated by action potential-evoked release (during high frequency stimulation of the mossy fibres), tonic inhibition and superfused ACh are 1:3:12, indicating that tonic and ACh-mediated inhibition may play a major role in regulating granule cell firing.",
author = "Rossi, {David J.} and Martine Hamann and David Attwell",
year = "2003",
month = "4",
day = "1",
doi = "10.1113/jphysiol.2002.036459",
language = "English (US)",
volume = "548",
pages = "97--110",
journal = "Journal of Physiology",
issn = "0022-3751",
publisher = "Wiley-Blackwell",
number = "1",

}

TY - JOUR

T1 - Multiple modes of GABAergic inhibition of rat cerebellar granule cells

AU - Rossi, David J.

AU - Hamann, Martine

AU - Attwell, David

PY - 2003/4/1

Y1 - 2003/4/1

N2 - Cerebellar granule cells are inhibited phasically by GABA released synaptically from Golgi cells, but are inhibited more powerfully by tonic activity of high affinity α6 subunit-containing GABAA receptors. During development the tonic activity is generated by the accumulation of GABA released by action potentials, but in the adult the tonic activity is independent of action potentials. Here we show that in adult rats the tonic activation of GABAA receptors is produced by non-vesicular transmitter release and is reduced by the activity of GAT-1 and GAT-3 GABA transporters, demonstrating that alterations of GABA uptake will modulate information flow through granule cells. Acetylcholine (ACh) evokes a large Ca2+-dependent but action potential-independent release of GABA, which activates α6 subunit-containing GABAA receptors. These data show that three separate modes of transmitter release can activate GABAA receptors in adult cerebellar granule cells: action potential-evoked exocytotic GABA release, non-vesicular release, and ACh-evoked Ca2+-dependent release independent of action potentials. The relative magnitudes of the inhibitory charge transfers generated by action potential-evoked release (during high frequency stimulation of the mossy fibres), tonic inhibition and superfused ACh are 1:3:12, indicating that tonic and ACh-mediated inhibition may play a major role in regulating granule cell firing.

AB - Cerebellar granule cells are inhibited phasically by GABA released synaptically from Golgi cells, but are inhibited more powerfully by tonic activity of high affinity α6 subunit-containing GABAA receptors. During development the tonic activity is generated by the accumulation of GABA released by action potentials, but in the adult the tonic activity is independent of action potentials. Here we show that in adult rats the tonic activation of GABAA receptors is produced by non-vesicular transmitter release and is reduced by the activity of GAT-1 and GAT-3 GABA transporters, demonstrating that alterations of GABA uptake will modulate information flow through granule cells. Acetylcholine (ACh) evokes a large Ca2+-dependent but action potential-independent release of GABA, which activates α6 subunit-containing GABAA receptors. These data show that three separate modes of transmitter release can activate GABAA receptors in adult cerebellar granule cells: action potential-evoked exocytotic GABA release, non-vesicular release, and ACh-evoked Ca2+-dependent release independent of action potentials. The relative magnitudes of the inhibitory charge transfers generated by action potential-evoked release (during high frequency stimulation of the mossy fibres), tonic inhibition and superfused ACh are 1:3:12, indicating that tonic and ACh-mediated inhibition may play a major role in regulating granule cell firing.

UR - http://www.scopus.com/inward/record.url?scp=0037384996&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037384996&partnerID=8YFLogxK

U2 - 10.1113/jphysiol.2002.036459

DO - 10.1113/jphysiol.2002.036459

M3 - Article

C2 - 12588900

AN - SCOPUS:0037384996

VL - 548

SP - 97

EP - 110

JO - Journal of Physiology

JF - Journal of Physiology

SN - 0022-3751

IS - 1

ER -