Dataset Information

Group I metabotropic glutamate receptors inhibit GABA release at interneuron-Purkinje cell synapses through endocannabinoid production.

ABSTRACT: Actions of endocannabinoids in the cerebellum can be demonstrated following distinct stimulation protocols in Purkinje cells. First, depolarization-induced elevations of intracellular Ca2+ lead to the suppression of neurotransmitter release from both inhibitory and excitatory afferents. In another case, postsynaptic group I metabotropic glutamate receptors (mGluRs) trigger a strong inhibition of the glutamatergic inputs from parallel and climbing fibers. Both pathways involve endocannabinoids retrogradely acting on type 1 cannabinoid receptors (CB1Rs) at presynaptic terminals. Here, we show that group I mGluR activation also depresses GABAergic transmission at the synapses between molecular layer interneurons and Purkinje cells. Using paired recordings, we found that application of the group I mGluR agonist (RS)-3,5-dihydroxyphenylglycine reduced the evoked IPSCs in Purkinje cells. This effect was independent of postsynaptic Ca2+ increases and was completely blocked by a CB1R antagonist. Experiments performed with the GTP-analogues GDP-betaS and GTP-gammaS provided evidence that endocannabinoids released after G-protein activation can also inhibit GABAergic inputs onto nearby, unstimulated Purkinje cells. Block of the enzymes DAG lipase or phospholipase C reduced the group I mGluR-dependent inhibition, suggesting that 2-arachidonyl glycerol could act as retrograde messenger. Finally, group I mGluR activation by brief bursts of activity of the parallel fibers induced a short-lived depression of spontaneous IPSCs via presynaptic CB1Rs. Our results reveal a mechanism with potential physiological importance, by which glutamatergic synapses induce an endocannabinoid-mediated inhibition of the GABAergic inputs onto Purkinje cells.

SUBMITTER: Galante M

PROVIDER: S-EPMC6729473 | biostudies-literature | 2004 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Group I metabotropic glutamate receptors inhibit GABA release at interneuron-Purkinje cell synapses through endocannabinoid production.

Galante Micaela M Diana Marco A MA

The Journal of neuroscience : the official journal of the Society for Neuroscience 20040501 20

Actions of endocannabinoids in the cerebellum can be demonstrated following distinct stimulation protocols in Purkinje cells. First, depolarization-induced elevations of intracellular Ca2+ lead to the suppression of neurotransmitter release from both inhibitory and excitatory afferents. In another case, postsynaptic group I metabotropic glutamate receptors (mGluRs) trigger a strong inhibition of the glutamatergic inputs from parallel and climbing fibers. Both pathways involve endocannabinoids re ...[more]

PMID: 15152047

Similar Datasets

Project description:It is well established that selective activation of group I metabotropic glutamate (mGlu) receptors induces LTD of synaptic transmission at Schaffer collateral-CA1 synapses. In contrast, application of 1S,3R-ACPD, a mixed agonist at group I and group II mGlu receptors, induces LTP. Using whole-cell recordings from CA1 pyramidal cells and field recordings in the hippocampal CA1 region, we investigated the specific contribution of group II mGlu receptors to synaptic plasticity at Schaffer collateral-CA1 synapses in acute slices of adult mice. Pharmacological activation of group II mGlu receptors (mGlu2 and mGlu3 receptors) with the specific agonist LY354740 in conjunction with electrical stimulation induced postsynaptic LTP. This form of plasticity requires coactivation of NMDA receptors (NMDARs). Group II mGlu receptor activation led to PKC-dependent phosphorylation of the GluN1 subunit. We found that both synaptic and extrasynaptic NMDARs, which are differentially modulated by mGlu2 and mGlu3 receptors, contribute to LTP induction. Furthermore, LTP initiated by activation of group II mGlu receptors was not occluded by LTP induced with high-frequency trains of stimuli. However, the phosphorylation of NMDARs mediated by group II mGlu receptor activation led to a priming effect that enhanced subsequent high-frequency stimulation-induced LTP. These findings reveal a novel metaplastic mechanism through which group II mGlu receptors modulate synaptic function at the Schaffer collateral input to CA1 pyramidal cells, thereby lowering the threshold to induce plasticity.Significance statementThe group II metabotropic glutamate (mGlu II) receptors exert a well characterized action on presynaptic neuron terminals to modulate neurotransmitter release. Here, we show that these receptors also have postsynaptic effects in promoting the induction of synaptic plasticity. Using an electrophysiological approach including field and whole-cell patch recording in hippocampi from wild-type and transgenic mice, we show that activation of group II mGlu receptors enhances NMDA receptor (NMDAR)-mediated currents through PKC-dependent phosphorylation. This priming of NMDARs lowers the threshold for the induction of LTP of synaptic transmission. These findings may also provide new insights into the mechanisms through which drugs targeting mGlu II receptors alleviate hypoglutamatergic conditions such as those occurring in certain brain disorders such as schizophrenia.

Dataset Information

Group I metabotropic glutamate receptors inhibit GABA release at interneuron-Purkinje cell synapses through endocannabinoid production.

Publications

Group I metabotropic glutamate receptors inhibit GABA release at interneuron-Purkinje cell synapses through endocannabinoid production.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets