Synaptic activation of AMPA receptors inhibits GABA release from cerebellar interneurons

Satake, Shin’Ichiro; Saitow, Fumihito; Yamada, Jun; Konishi, Shiro

doi:10.1038/75718

Cited by 116 publications

(133 citation statements)

References 37 publications

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“…Together with the present results, these findings suggest activating mGluR2/3 receptors could attenuate hypoglutamatergia by increasing the number of active NMDA-R, possibly via the NMDA-R regulating SRC kinase (Trepanier et al, 2013). mGluR2/3 activation has also been shown to increase non-NMDA glutamate receptor levels (Wang et al, 2013), which could contribute to the restoration of GABAA-R binding levels through reduced GABA release (Drew and Vaughan, 2004;Satake et al, 2000). Finally, Gorrie and colleagues have reported that more than 6 h are required for the synthesis of GABAA-R and its integration into the cell membrane (Gorrie et al, 1997), with GABAA-receptors more likely being recycled back into the membrane than replaced with new receptors (Thomas et al, 2005).…”

Section: The Mglur2/3 Agonist Ly379268 Restores Nmda-r and Gabaa-r Exsupporting

confidence: 53%

mGluR2/3 agonist LY379268 rescues NMDA and GABAA receptor level deficits induced in a two-hit mouse model of schizophrenia

et al. 2016

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Rationale An imbalance of excitatory and inhibitory neurotransmission underlies the glutamate hypothesis of schizophrenia. Agonists of group II metabotropic glutamate receptors, mGluR2/3, have been proposed as novel therapeutic agents to correct this imbalance. However, the influence of mGluR2/3 activity on excitatory and inhibitory neurotransmitter receptors has not been explored. Objectives We aimed to investigate the ability of a novel mGluR2/3 agonist, LY379268, to modulate the availability of the excitatory N-methyl-daspartate receptor (NMDA-R) and the inhibitory gamma-aminobutyrate-A receptor (GABAA-R), in a twohit mouse model of schizophrenia. Methods Wild type (WT) and heterozygous neuregulin 1 transmembrane domain mutant mice (NRG1 HET) were treated daily with phencyclidine (10 mg/kg ip) or saline for 14 days. After a 14-day washout, an acute dose of the mGluR2/3 agonist LY379268 (3 mg/kg), olanzapine (antipsychotic drug comparison, 1.5 mg/kg), or saline was administered. NMDA-R and GABAA-R binding densities were examined by receptor autoradiography in several schizophrenia-relevant brain regions. Results In both WT and NRG1 HET mice, phencyclidine treatment significantly reduced NMDA-R and GABAA-R binding density in the prefrontal cortex, hippocampus, and nucleus accumbens. Acute treatment with LY379268 restored NMDA-R and GABAA-R levels in the two-hit mouse model comparable to olanzapine. Conclusions We demonstrate that the mGluR2/3 agonist LY379268 restores excitatory and inhibitory deficits with similar efficiency as olanzapine in our two-hit schizophrenia mouse model. This study significantly contributes to our understanding of the mechanisms underlying the therapeutic effects of LY379268 and supports the use of agents aimed at mGluR2/3. Disciplines Medicine and Health Sciences Publication DetailsEngel, M., Snikeris, P., Matosin, N., Newell, K. Anne., Huang, X. & Frank, E. (2016). mGluR2/3 agonist LY379268 rescues NMDA and GABAA receptor level deficits induced in a two-hit mouse model of schizophrenia. Psychopharmacology, 233 (8) AcknowledgmentsThis work was supported by the Schizophrenia Research Institute, utilising infrastructure funding from the NSW Ministry of Health. LY379268 was kindly gifted by Eli Lilly & Co (Indianapolis, USA). The funding bodies had no role in the study design, data collection and publication decisions. 2 AbstractRationale An imbalance of excitatory and inhibitory neurotransmission underlies the glutamate hypothesis of schizophrenia. Agonists of Group II metabotropic glutamate receptors, mGluR2/3, have been proposed as novel therapeutic agents to correct this imbalance. However, the influence of mGluR2/3 activity on excitatory and inhibitory neurotransmitter receptors has not been explored.Objectives We aimed to investigate the ability of a novel mGluR2/3 agonist, LY379268, to modulate the availability of the excitatory N-methyl-D-aspartate receptor (NMDA-R) and the inhibitory gamma-aminobutyrate-A receptor (GABAA-R), in a two-hit mouse model of schizophrenia.Me...

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Section: The Mglur2/3 Agonist Ly379268 Restores Nmda-r and Gabaa-r Exsupporting

confidence: 53%

mGluR2/3 agonist LY379268 rescues NMDA and GABAA receptor level deficits induced in a two-hit mouse model of schizophrenia

et al. 2016

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“…GluR4 immunogold particles are observed in presynaptic structures at the hair cell ribbon synapse (43) and at the end bulb of Held synapse in the anteroventral cochlear nucleus of auditory brainstem (44). At cerebellar inhibitory synapses (8,45) and spinal cord excitatory synapses (7), presynapticAMPARsinhibittransmitterrelease.Thus,theAMPARmediated presynaptic inhibition may be widespread among central synapses.…”

Section: Discussionmentioning

confidence: 99%

G protein-dependent presynaptic inhibition mediated by AMPA receptors at the calyx of Held

Takago

Nakamura

Takahashi

2005

Proc. Natl. Acad. Sci. U.S.A.

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The ␣-amino-3-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) is an ionotropic receptor mediating excitatory synaptic transmission, but it can also interact with intracellular messengers. Here we report that, at the calyx of Held in the rat auditory brainstem, activation of AMPARs induced inward currents in the nerve terminal and inhibited presynaptic Ca 2؉ currents (IpCa), thereby attenuating glutamatergic synaptic transmission. The AM-PAR-mediated I pCa inhibition was disinhibited by a strong depolarizing pulse and occluded by the nonhydrolyzable GTP analog GTP␥S loaded into the terminal. We conclude that functional AMPARs are expressed at the calyx of Held nerve terminal and that their activation inhibits voltage-gated Ca 2؉ channels by an interaction with heterotrimeric GTP-binding proteins (G proteins). Thus, at a central glutamatergic synapse, presynaptic AMPARs have a metabotropic nature and regulate transmitter release by means of G proteins.calcium channel ͉ excitatory postsynaptic current ͉ synapse ͉ glutamate

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“…Therefore, at the moment little is known on the relation between synaptically induced calcium transients and DSI/DSE in Purkinje cells. Paradoxically, the only report concerning the effects of high-frequency, glutamatergic fiber stimulation on GABAergic transmission has shown an inhibition after climbing fiber activation which is not dependent on CB1Rs, but rather on presynaptic ionotropic glutamate receptors (Satake et al, 2000).…”

Section: Functional Implications Of Dsi In the Cerebellummentioning

confidence: 99%

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

234

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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Synaptic activation of AMPA receptors inhibits GABA release from cerebellar interneurons

Cited by 116 publications

References 37 publications

mGluR2/3 agonist LY379268 rescues NMDA and GABAA receptor level deficits induced in a two-hit mouse model of schizophrenia

mGluR2/3 agonist LY379268 rescues NMDA and GABAA receptor level deficits induced in a two-hit mouse model of schizophrenia

G protein-dependent presynaptic inhibition mediated by AMPA receptors at the calyx of Held

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

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