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Details

Autor(en) / Beteiligte
Titel
Presynaptic, Activity-Dependent Modulation of Cannabinoid Type 1 Receptor-Mediated Inhibition of GABA Release
Ist Teil von
  • The Journal of neuroscience, 2006-02, Vol.26 (5), p.1465-1469
Ort / Verlag
United States: Soc Neuroscience
Erscheinungsjahr
2006
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
  • Endocannabinoid signaling couples activity-dependent rises in postsynaptic Ca2+ levels to decreased presynaptic GABA release. Here, we present evidence from paired recording experiments that cannabinoid-mediated inhibition of GABA release depends on the firing rates of the presynaptic interneurons. Low-frequency action potentials in post hoc identified cholecystokinin-positive CA1 basket cells elicited IPSCs in the postsynaptic pyramidal cells that, as expected, were fully abolished by the exogenous application of the cannabinoid receptor agonist WIN55,212-2 [R-(+)-(2,3-dihydro-5-methyl-3-[(4-morpholinyl)methyl]pyrol[1,2,3-de]-1,4-benzoxazin-6-yl)(1-naphthalenyl) methanone monomethanesulfonate] at 5 microM. However, the presynaptic basket cells recovered from the cannabinoid agonist-induced inhibition of GABA release when the presynaptic firing rate was increased to > or =20 Hz. Pharmacological experiments showed that the recovered transmission was exclusively dependent on presynaptic N-type Ca2+ channels. Furthermore, the increased presynaptic firing could also overcome even complete depolarization-induced suppression of inhibition, indicating that the magnitude of DSI markedly depends on the activity levels of basket cells. These results reveal a new locus of activity-dependent modulation for endocannabinoid signaling and suggest that endocannabinoid-mediated inhibition of GABA release may differ in distinct behavioral states.

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