Metabotropic Glutamate Receptors Drive the Endocannabinoid System in Hippocampus

Varma, Namita; Carlson, Gerald M.; Ledent, Catherine; Alger, Bradley E.

doi:10.1523/jneurosci.21-24-j0003.2001

Cited by 364 publications

(325 citation statements)

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“…Interestingly, we found that suspending synaptic activation or pharmacological blockade of mGluR also led to the extension of the cortical-tothalamic cooperation window, suggesting that synaptic activation, presumably through activation of mGluR leads to the release of eCBs that acting on CB1 receptors restricts synaptic cooperation. This is supported by previous studies showing a modulation of eCBs release by mGluR activation (Varma et al, 2001;Azad et al, 2004). Our results do not suggest that CB1 receptor activation regulates the synthesis of PRPs but rather modulates the ability of thalamic synapse to capture PRPs or to express LTP.…”

Section: Discussionsupporting

confidence: 90%

“…We found that inhibition of CB1 receptors extends the time window for cortical-to-thalamic cooperation (Figure 5b), similar to what we observed when synaptic activation was suspended. eCBs can be released in the amygdala through the activation of metabotropic mGluRs (Azad et al, 2004;Varma et al, 2001); hence, one possibility is that synaptic activation triggers eCB release through mGluR activation. To test this, we repeated the experiment described above and inhibited mGluR activation by applying (RS)-a-MCPG (200 mM) during the time interval between weak thalamic stimulation and cortical strong stimulation (30 min).…”

Section: Synaptic Cooperation Between Cortical and Thalamic Inputs Hamentioning

confidence: 99%

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Asymmetrical Synaptic Cooperation between Cortical and Thalamic Inputs to the Amygdale

Fonseca

2013

Neuropsychopharmacol

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Fear conditioning, a form of associative learning is thought to involve the induction of an associative long-term potentiation of cortical and thalamic inputs to the lateral amygdala. Here, we show that stimulation of the thalamic input can reinforce a transient form of plasticity (E-LTP) induced by weak stimulation of the cortical inputs. This synaptic cooperation occurs within a time window of 30 min, suggesting that synaptic integration at amygdala synapses can occur within large time windows. Interestingly, we found that synaptic cooperation is not symmetrical. Reinforcement of a thalamic E-LTP by subsequent cortical stimulation is only observed within a shorter time window. We found that activation of endocannabinoid CB1 receptors is involved in the time restriction of thalamic and cortical synaptic cooperation in an activity-dependent manner. Our results support the hypothesis that synaptic cooperation can underlie associative learning and that synaptic tagging and capture is a general mechanism in synaptic plasticity.

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Section: Discussionsupporting

confidence: 90%

Section: Synaptic Cooperation Between Cortical and Thalamic Inputs Hamentioning

confidence: 99%

Asymmetrical Synaptic Cooperation between Cortical and Thalamic Inputs to the Amygdale

Fonseca

2013

Neuropsychopharmacol

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“…Indeed, Varma et al (2001) (and later Ohno-Shosaku et al, 2002a) confirmed that group I mGluR activation also led to the production of endocannabinoids in hippocampal CA1 cells, and showed that this pathway, although not mediating DSI, had a powerful modulatory effect on the phenomenon. Further work extended these findings by showing that the activation of muscarinic receptors of the m1 and m3 subtypes had effects similar to those of group I mGluR activation (Martin & Alger, 1999;Kim et al, 2002;Ohno-Shosaku et al, 2003).…”

Section: The G-protein Coupled Receptor Pathway Of Retrograde Inhibitionmentioning

confidence: 87%

Endocannabinoid‐mediated short‐term synaptic plasticity: depolarization‐induced suppression of inhibition (DSI) and depolarization‐induced suppression of excitation (DSE)

Diana

Marty

2004

British J Pharmacology

238

177

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Depolarization-induced suppression of inhibition (DSI) and depolarization-induced suppression of excitation (DSE) are two related forms of short-term synaptic plasticity of GABAergic and glutamatergic transmission, respectively. They are induced by calcium concentration increases in postsynaptic cells and are mediated by the release of a retrograde messenger, which reversibly inhibits afferent synapses via presynaptic mechanisms. We review here:(1) The evidence accumulated during the 1990s that has led to the conclusion that DSI/DSE rely on retrograde signaling. (2) The more recent research that has led to the identification of endocannabinoids as the retrograde messengers responsible for DSI/DSE. (3) The possible mechanisms by which presynaptic type 1 cannabinoid receptors reduce synaptic efficacy during DSI/DSE. (4) The possible modes of induction of DSI/DSE by physiological activity patterns, and the partially conflicting evaluations of the calcium concentration increases required for cannabinoid synthesis. (5) Finally, the relation between DSI/DSE and other forms of long-and short-term synaptic inhibition, which were more recently associated with the production of endocannabinoids by postsynaptic cells.We conclude that recent studies on DSI/DSE have uncovered a specific and original mode of action for endocannabinoids in the brain, and that they have opened new avenues to understand the role of retrograde signaling in central synapses.

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“…It has been demonstrated in a number of brain regions that activation of group I mGluRs inhibits GABAergic synaptic transmission indirectly via the endocannabinoid system (Maejima et al, 2001;Varma et al, 2001;Ohno-Shosaku et al, 2002;Galante and Diana, 2004). We therefore examined whether the TBOAinduced inhibition of GABAergic transmission was also mediated via endocannabinoids within the PAG.…”

Section: Tboa and Group I Mglur Activation Reduce Gabaergic Transmissmentioning

confidence: 99%

Glutamate Spillover Modulates GABAergic Synaptic Transmission in the Rat Midbrain Periaqueductal Grey via Metabotropic Glutamate Receptors and Endocannabinoid Signaling

Drew

Mitchell²,

Vaughan³

2008

J. Neurosci.

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Glutamate spillover regulates GABAergic synaptic transmission at several CNS synapses via presynaptic ionotropic and metabotropic glutamate receptors (mGluRs). We have previously demonstrated that activation of group I-III mGluRs inhibits GABAergic transmission in the midbrain periaqueductal gray (PAG), a region involved in organizing behavioral responses to threat, stress, and pain. Here, we examined the role of glutamate spillover in the modulation of GABAergic transmission in the PAG. Using whole-cell recordings from rat PAG slices, we found that evoked IPSCs were reduced by the nonspecific glutamate transport blockers DL-threo-␤-benzyloxyaspartic acid (TBOA) and L-trans-pyrrolidine-2,4-dicarboxylic acid, but not by the glial GLT1-specific blocker dihydrokainate. In contrast, TBOA had no effect on evoked IPSCs when glutamate uptake into the postsynaptic neuron was selectively impaired. TBOA increased the pairedpulse ratio of evoked IPSCs and reduced the rate but not the amplitude of spontaneous miniature IPSCs. The effect of TBOA on evoked IPSCs was abolished by the broad-spectrum mGluR antagonist (2S)-2-amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid (100 M), reduced by the mGluR5-specific antagonist 2-methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP) and mimicked by the mGluR1/5 agonist (RS)-3,5-dihydroxyphenylglycine (DHPG). Furthermore, the effects of both TBOA and DHPG were reduced by the cannabinoid CB1 receptor antagonist 1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-1-piperidinyl-1H-pyrazole-3-carboxamide (AM251). Finally, although MPEP and AM251 had no effect on single evoked IPSCs, they increased evoked IPSCs during repetitive stimulation. These results indicate that neuronal glutamate transporters limit mGluR5 activation and endocannabinoid signaling, but may be overwhelmed during conditions of elevated glutamate release. Thus, neuronal glutamate transporters play a key role in regulating endocannabinoid-mediated cross talk between glutamatergic and GABAergic synapses within the PAG.

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Metabotropic Glutamate Receptors Drive the Endocannabinoid System in Hippocampus

Cited by 364 publications

References 44 publications

Asymmetrical Synaptic Cooperation between Cortical and Thalamic Inputs to the Amygdale

Asymmetrical Synaptic Cooperation between Cortical and Thalamic Inputs to the Amygdale

Endocannabinoid‐mediated short‐term synaptic plasticity: depolarization‐induced suppression of inhibition (DSI) and depolarization‐induced suppression of excitation (DSE)

Glutamate Spillover Modulates GABAergic Synaptic Transmission in the Rat Midbrain Periaqueductal Grey via Metabotropic Glutamate Receptors and Endocannabinoid Signaling

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