D2Dopamine Receptor Activation Facilitates Endocannabinoid-Mediated Long-Term Synaptic Depression of GABAergic Synaptic Transmission in Midbrain Dopamine Neurons via cAMP-Protein Kinase A Signaling
Open Access
- 24 December 2008
- journal article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 28 (52), 14018-14030
- https://doi.org/10.1523/jneurosci.4035-08.2008
Abstract
Endocannabinoid (eCB) signaling mediates short-term and long-term synaptic depression (LTD) in many brain areas. In the ventral tegmental area (VTA) and striatum, D2dopamine receptors cooperate with group I metabotropic glutamate receptors (mGluRs) to induce eCB-mediated LTD of glutamatergic excitatory and GABAergic inhibitory (I-LTD) synaptic transmission. Because D2receptors and group I mGluR agonists are capable of inducing the release of eCBs, the predominant hypothesis is that the cooperation between these receptors to induce eCB-mediated synaptic depression results from the combined activation of type I cannabinoid (CB1) receptors by the eCBs. By determining the downstream effectors for D2receptor and group I mGluR activation in VTA dopamine neurons, we show that group I mGluR activation contributes to I-LTD induction by enhancing eCB release and CB1receptor activation. However, D2receptor activation does not enhance CB1receptor activation, but facilitates I-LTD induction via direct inhibition of cAMP-dependent protein kinase A (PKA) signaling. We further demonstrate that cAMP/PKA signaling pathway is the downstream effector for CB1receptors and is required for eCB-mediated I-LTD induction. Our results suggest that D2receptors and CB1receptors target the same downstream effector cAMP/PKA signaling pathway to induce I-LTD and D2receptor activation facilitates eCB-mediated I-LTD in dopamine neurons not by enhancing CB1receptor activation, but by enhancing its downstream effects.Keywords
This publication has 73 references indexed in Scilit:
- Interneuron activity controls endocannabinoid-mediated presynaptic plasticity through calcineurinProceedings of the National Academy of Sciences of the United States of America, 2008
- Localization of N‐acyl phosphatidylethanolamine phospholipase D (NAPE‐PLD) expression in mouse brain: A new perspective on N‐acylethanolamines as neural signaling moleculesJournal of Comparative Neurology, 2007
- Striatal Medium Spiny Neurons Terminate in a Distinct Region in the Lateral Hypothalamic Area and Do Not Directly Innervate Orexin/Hypocretin- or Melanin-Concentrating Hormone-Containing NeuronsJournal of Neuroscience, 2007
- Endocannabinoid-Mediated Long-Term Plasticity Requires cAMP/PKA Signaling and RIM1αNeuron, 2007
- The ventral tegmental area revisited: is there an electrophysiological marker for dopaminergic neurons?The Journal of Physiology, 2006
- Frequency-specific and D 2 receptor-mediated inhibition of glutamate release by retrograde endocannabinoid signalingProceedings of the National Academy of Sciences of the United States of America, 2006
- Presynaptic Mechanism Underlying cAMP-Dependent Synaptic PotentiationJournal of Neuroscience, 2004
- SHORT COMMUNICATION Inhibition of GABAergic neurotransmission in the ventral tegmental area by cannabinoidsEuropean Journal of Neuroscience, 2002
- Cocaine and Amphetamine Depress Striatal GABAergic Synaptic Transmission through D2 Dopamine ReceptorsNeuropsychopharmacology, 2002
- Dopamine D2 Receptors in Signal Transduction and BehaviorCritical Reviews™ in Neurobiology, 1997