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

Jimok Kim, Bradley E. Alger

Research output: Contribution to journalArticlepeer-review

124 Scopus citations


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
Issue number5
StatePublished - May 2010
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)


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