Reduction in endocannabinoid tone is a homeostatic mechanism for specific inhibitory synapses

Jimok Kim, Bradley E. Alger

Research output: Contribution to journalArticle

106 Citations (Scopus)

Abstract

When chronic alterations in neuronal activity occur, network gain is maintained by global homeostatic scaling of synaptic strength, but the stability of microcircuits can be controlled by unique adaptations that differ from the global changes. It is not understood how specificity of synaptic tuning is achieved. We found that, although a large population of inhibitory synapses was homeostatically scaled down after chronic inactivity, decreased endocannabinoid tone specifically strengthened a subset of GABAergic synapses that express cannabinoid receptors. In rat hippocampal slice cultures, a 3-5-d blockade of neuronal firing facilitated uptake and degradation of anandamide. The consequent reduction in basal stimulation of cannabinoid receptors augmented GABA release probability, fostering rapid depression of synaptic inhibition and on-demand disinhibition. This regulatory mechanism, mediated by activity-dependent changes in tonic endocannabinoid level, permits selective local tuning of inhibitory synapses in hippocampal networks.

Original languageEnglish (US)
Pages (from-to)592-600
Number of pages9
JournalNature Neuroscience
Volume13
Issue number5
DOIs
StatePublished - May 1 2010

Fingerprint

Endocannabinoids
Synapses
Cannabinoid Receptors
Foster Home Care
gamma-Aminobutyric Acid
Population

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Reduction in endocannabinoid tone is a homeostatic mechanism for specific inhibitory synapses. / Kim, Jimok; Alger, Bradley E.

In: Nature Neuroscience, Vol. 13, No. 5, 01.05.2010, p. 592-600.

Research output: Contribution to journalArticle

Kim, Jimok ; Alger, Bradley E. / Reduction in endocannabinoid tone is a homeostatic mechanism for specific inhibitory synapses. In: Nature Neuroscience. 2010 ; Vol. 13, No. 5. pp. 592-600.
@article{67e3b098dc71416a94e3aa6253e558b7,
title = "Reduction in endocannabinoid tone is a homeostatic mechanism for specific inhibitory synapses",
abstract = "When chronic alterations in neuronal activity occur, network gain is maintained by global homeostatic scaling of synaptic strength, but the stability of microcircuits can be controlled by unique adaptations that differ from the global changes. It is not understood how specificity of synaptic tuning is achieved. We found that, although a large population of inhibitory synapses was homeostatically scaled down after chronic inactivity, decreased endocannabinoid tone specifically strengthened a subset of GABAergic synapses that express cannabinoid receptors. In rat hippocampal slice cultures, a 3-5-d blockade of neuronal firing facilitated uptake and degradation of anandamide. The consequent reduction in basal stimulation of cannabinoid receptors augmented GABA release probability, fostering rapid depression of synaptic inhibition and on-demand disinhibition. This regulatory mechanism, mediated by activity-dependent changes in tonic endocannabinoid level, permits selective local tuning of inhibitory synapses in hippocampal networks.",
author = "Jimok Kim and Alger, {Bradley E.}",
year = "2010",
month = "5",
day = "1",
doi = "10.1038/nn.2517",
language = "English (US)",
volume = "13",
pages = "592--600",
journal = "Nature Neuroscience",
issn = "1097-6256",
publisher = "Nature Publishing Group",
number = "5",

}

TY - JOUR

T1 - Reduction in endocannabinoid tone is a homeostatic mechanism for specific inhibitory synapses

AU - Kim, Jimok

AU - Alger, Bradley E.

PY - 2010/5/1

Y1 - 2010/5/1

N2 - When chronic alterations in neuronal activity occur, network gain is maintained by global homeostatic scaling of synaptic strength, but the stability of microcircuits can be controlled by unique adaptations that differ from the global changes. It is not understood how specificity of synaptic tuning is achieved. We found that, although a large population of inhibitory synapses was homeostatically scaled down after chronic inactivity, decreased endocannabinoid tone specifically strengthened a subset of GABAergic synapses that express cannabinoid receptors. In rat hippocampal slice cultures, a 3-5-d blockade of neuronal firing facilitated uptake and degradation of anandamide. The consequent reduction in basal stimulation of cannabinoid receptors augmented GABA release probability, fostering rapid depression of synaptic inhibition and on-demand disinhibition. This regulatory mechanism, mediated by activity-dependent changes in tonic endocannabinoid level, permits selective local tuning of inhibitory synapses in hippocampal networks.

AB - When chronic alterations in neuronal activity occur, network gain is maintained by global homeostatic scaling of synaptic strength, but the stability of microcircuits can be controlled by unique adaptations that differ from the global changes. It is not understood how specificity of synaptic tuning is achieved. We found that, although a large population of inhibitory synapses was homeostatically scaled down after chronic inactivity, decreased endocannabinoid tone specifically strengthened a subset of GABAergic synapses that express cannabinoid receptors. In rat hippocampal slice cultures, a 3-5-d blockade of neuronal firing facilitated uptake and degradation of anandamide. The consequent reduction in basal stimulation of cannabinoid receptors augmented GABA release probability, fostering rapid depression of synaptic inhibition and on-demand disinhibition. This regulatory mechanism, mediated by activity-dependent changes in tonic endocannabinoid level, permits selective local tuning of inhibitory synapses in hippocampal networks.

UR - http://www.scopus.com/inward/record.url?scp=77951665718&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77951665718&partnerID=8YFLogxK

U2 - 10.1038/nn.2517

DO - 10.1038/nn.2517

M3 - Article

C2 - 20348918

AN - SCOPUS:77951665718

VL - 13

SP - 592

EP - 600

JO - Nature Neuroscience

JF - Nature Neuroscience

SN - 1097-6256

IS - 5

ER -