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PMID: 10662825 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Modulation of transmission during trains at a cerebellar synapse.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 20 ·No. 4 ·2000-02-15 ·Pages 1348-57

Kreitzer AC, Regehr WG

Abstract

Activity-dependent processes dynamically regulate synapses on the time scale of milliseconds to seconds. Here, we examine the factors governing synaptic strength during repetitive stimulation, both in control conditions and during presynaptic inhibition. Field recordings of presynaptic volleys, optical measurements of presynaptic calcium, and voltage-clamp recordings of postsynaptic currents were used to examine parallel fiber to Purkinje cell synapses in cerebellar brain slices at 34 degrees C. In control conditions, regular stimulus trains (1-50 Hz) evoked up to a 250% peak synaptic enhancement, whereas during irregular stimulation, a threefold variability in EPSC amplitude was observed. When initial EPSC amplitudes were reduced by 50%, either by lowering external calcium or by activating adenosine A(1) or GABA(B) receptors, the peak enhancement during regular trains was 500%, and synaptic variability during irregular trains was nearly sixfold. By contrast, changes in fiber excitability and calcium influx per pulse were small during trains. Presynaptic calcium measurements indicated that by pulse 10, stimulus-evoked calcium influx had increased by approximately 15%, which on the basis of the measured relationship between calcium influx and release corresponds to an EPSC enhancement of 50%. This enhancement was the same in all experimental conditions, even in the presence of N(6)-cyclopentyladenosine or baclofen, suggesting that repetitive stimulation does not relieve the G-protein inhibition of calcium channels by these modulators. Therefore, for our experimental conditions, changes in synaptic strength during trains are primarily attributable to residual calcium (Ca(res))-dependent short-term plasticities, and the actions of neuromodulators during repetitive stimulation result from their inhibition of initial calcium influx and the resulting effects on Ca(res) and calcium-driven processes.

MeSH Terms
Animals Baclofen/pharmacology Calcium/metabolism,pharmacology Cerebellum/physiology Electric Stimulation Excitatory Amino Acid Antagonists/pharmacology Excitatory Postsynaptic Potentials/drug effects,physiology GABA Antagonists/pharmacology GTP-Binding Proteins/physiology Glycine/analogs & derivatives,pharmacology In Vitro Techniques Nerve Fibers/drug effects,physiology Phosphinic Acids/pharmacology Presynaptic Terminals/physiology Propanolamines/pharmacology Purinergic P1 Receptor Antagonists Purkinje Cells/physiology Rats Rats, Sprague-Dawley Receptors, GABA-B/physiology Receptors, Purinergic P1/physiology Synapses/drug effects,physiology Xanthines/pharmacology
Chemicals
Excitatory Amino Acid Antagonists GABA Antagonists Phosphinic Acids Propanolamines Purinergic P1 Receptor Antagonists Receptors, GABA-B Receptors, Purinergic P1 Xanthines cyclopropyl-4-phosphonophenylglycine CGP 55845A 1,3-dipropyl-8-cyclopentylxanthine GTP-Binding Proteins Baclofen Calcium Glycine
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Kreitzer A C
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Regehr W G
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
0270-6474
Published
2000-02-15
Pages
1348-57
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6772360
Subset
IM
Grants
NINDS NIH HHS · R01 NS032405 · United States
NIMH NIH HHS · MH20017-02 · United States
NINDS NIH HHS · NS20017-02 · United States
NINDS NIH HHS · R01-NS32405-01 · United States
External Links
PubMed source PMC Full Text View journal details
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