Presynaptic, activity-dependent modulation of cannabinoid type 1 receptor-mediated inhibition of GABA release

TY - JOUR

T1 - Presynaptic, activity-dependent modulation of cannabinoid type 1 receptor-mediated inhibition of GABA release

AU - Földy, Csaba

AU - Neu, Axel

AU - Jones, Mathew V

AU - Soltesz, Ivan

PY - 2006/2/1

Y1 - 2006/2/1

N2 - 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.

AB - 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.

KW - Action Potentials

KW - Animals

KW - Benzoxazines

KW - Calcium Channels, N-Type

KW - Cannabinoids

KW - Cholecystokinin

KW - Evoked Potentials

KW - Hippocampus

KW - Interneurons

KW - Morpholines

KW - Naphthalenes

KW - Neural Inhibition

KW - Neuronal Plasticity

KW - Patch-Clamp Techniques

KW - Presynaptic Terminals

KW - Pyramidal Cells

KW - Rats

KW - Rats, Sprague-Dawley

KW - Receptor, Cannabinoid, CB1

KW - Synaptic Transmission

KW - gamma-Aminobutyric Acid

U2 - 10.1523/JNEUROSCI.4587-05.2006

DO - 10.1523/JNEUROSCI.4587-05.2006

M3 - SCORING: Journal article

C2 - 16452670

VL - 26

SP - 1465

EP - 1469

JO - J NEUROSCI

JF - J NEUROSCI

SN - 0270-6474

IS - 5

ER -