GABAA receptor-mediated presynaptic inhibition on glutamatergic transmission

Yamamoto, Sokatsu; Yoshimura, Michihiro; Shin, Min Chul; Wakita, Masahito; Nonaka, Kiku; Akaike, Norio

doi:10.1016/j.brainresbull.2010.10.007

Cited by 29 publications

(40 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Likewise, glutamatergic eEPSCs were isolated from GABAergic eIPSCs by recording them at a V H of Ϫ65 mV, close to the Cl Ϫ equilibrium potential (E Cl ) (Yamamoto et al, 2011).…”

Section: Methodsmentioning

confidence: 99%

“…This preparation involves mechanically dissociated neurons with adherent functional presynaptic terminals (Akaike and Moorhouse, 2003) and offers advantages for determining the locus of action of a neuromodulator such as EtOH because surrounding tissues, such as adjacent neurons and glia cells, are absent. We have identified presynaptic GABA A receptors on both GABAergic and glutamatergic nerve terminals projecting to hippocampal CA1 and CA3 neurons and spinal sacral dorsal commissural nucleus neurons that can modulate GABA and glutamate release evoked by focal electrical stimulation (Matsuura et al, 2011;Yamamoto et al, 2011). To clarify more precisely EtOH's actions on excitatory and inhibitory transmission, we report here the effects of EtOH on presynaptic GABA A receptors at single GABAergic and glutamatergic synapses in rat hippocampal CA1 and CA3 pyramidal neurons, using this synaptic bouton preparation.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of Ethanol on GABA_A Receptors in GABAergic and Glutamatergic Presynaptic Nerve Terminals

Wakita¹,

Shin²,

Iwata³

et al. 2012

J Pharmacol Exp Ther

Self Cite

View full text Add to dashboard Cite

Ethanol (EtOH) has a number of behavioral effects, including intoxication, amnesia, and/or sedation, that are thought to relate to the activation of GABA A receptors. However, GABA A receptors at different cellular locations have different sensitivities to EtOH. The present study used the "synaptic bouton" preparation where we could stimulate nerve endings on mechanically dissociated single rat hippocampal CA1 and CA3 pyramidal neurons and investigate the effects of EtOH on presynaptic and postsynaptic GABA A receptors. Low concentrations of EtOH (10 mM) had no effect on postsynaptic GABA A and glutamate receptors or voltage-dependent Na ϩ and Ca 2ϩ channels. Higher concentrations (Ն100 mM) could significantly inhibit these current responses. EtOH at 10 mM had no direct effect on inhibitory postsynaptic currents (IPSCs) and excitatory postsynaptic currents (EPSCs) evoked by focal stimulation of single boutons [evoked IPSCs (eIPSCs) and evoked EPSCs (eEPSCs)]. However, coapplication of 10 mM EtOH with muscimol decreased the amplitude of eIPSCs and eEPSCs and increased their paired-pulse ratio. The effects on eEPSCs were reversed by bicuculline. Coapplication of muscimol and EtOH significantly increased the frequency of spontaneous IPSCs and EPSCs. The EtOH effects on the postsynaptic responses and eEPSCs were similar in neurons from neonatal and mature rats. These results revealed that low concentrations of EtOH can potentiate the activation of presynaptic GABA A receptors to inhibit evoked GABA and glutamate release. These results indicate a high sensitivity of presynaptic GABA A receptor to EtOH, which needs to be accounted for when considering the cellular mechanisms of EtOH's physiological responses.

show abstract

“…Likewise, glutamatergic eEPSCs were isolated from GABAergic eIPSCs by recording them at a V H of Ϫ65 mV, close to the Cl Ϫ equilibrium potential (E Cl ) (Yamamoto et al, 2011).…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of Ethanol on GABA_A Receptors in GABAergic and Glutamatergic Presynaptic Nerve Terminals

Wakita¹,

Shin²,

Iwata³

et al. 2012

J Pharmacol Exp Ther

Self Cite

View full text Add to dashboard Cite

show abstract

“…For dissociation, slices were transferred into a 35-mm culture dish (Primaria 3801; Becton Dickinson, Rutherford, NJ, USA) containing the standard external solution (see below), and the region of the SDCN was identified under a binocular microscope (SMZ645; Nikon, Tokyo). Similarly, the brain slice preparation containing the region of hippocampal CA3 neurons was prepared (7). Full details of the mechanical dissociation procedure have been described previously (4,5,7,13).…”

Section: Preparation Of 'Synaptic Bouton Preparations'mentioning

confidence: 99%

“…Similarly, the brain slice preparation containing the region of hippocampal CA3 neurons was prepared (7). Full details of the mechanical dissociation procedure have been described previously (4,5,7,13). Mechanically dissociated SDCN or CA3 neurons were allowed to settle and adhere to the bottom of the dish for at least 15 min before recordings.…”

Section: Preparation Of 'Synaptic Bouton Preparations'mentioning

confidence: 99%

See 1 more Smart Citation

Neurotoxin A2NTX Blocks Fast Inhibitory and Excitatory Transmitter Release From Presynaptic Terminals

et al. 2012

Self Cite

View full text Add to dashboard Cite

Abstract. Our recent study showed a possibility that newly developed A2 type botulinum toxin (A2NTX) inhibits both spontaneous and evoked transmitter release from inhibitory (glycinergic or GABAergic) and excitatory (glutamatergic) nerve terminals using rat spinal sacral dorsal commissural nucleus neurons. In the present study, to determine the modulatory effect of A2NTX on glycinergic and glutamatergic release probabilities, we tested the effects of A2NTX on a single inhibitory or excitatory nerve ending adherent to a dissociated neuron that was activated by pairedpulse stimuli by using the focal electrical stimulation technique. The results of the present pairedpulse experiments showed clearly that A2NTX enhanced paired-pulse facilitation of evoked glycinergic inhibitory postsynaptic currents and glutamatergic excitatory postsynaptic currents and increased the failure rate (Rf) of the first postsynaptic currents (P 1 ) and both the responses. These effects of A2NTX on the amplitude and Rf of the P 1 and the second postsynaptic currents (P 2 ) and paired-pulse ratio were rescued by application of 4-aminophthalimide. In summary, the present results showed that A2NTX acts purely presynaptically and inhibits the release machinery of transmitters such as glycine and glutamate, and the transmitter release machinery became less sensitive to intracellular free-Ca 2+ in A2NTX poisoned nerve terminals.

show abstract

Neurosteroid allopregnanolone inhibits glutamate release from rat cerebrocortical nerve terminals

Chang

Hsieh

Huang

et al. 2018

Synapse

View full text Add to dashboard Cite

Allopregnanolone, an active metabolite of progesterone, has been reported to exhibit neuroprotective activity in several preclinical models. Considering that the excitotoxicity caused by excessive glutamate is implicated in many brain disorders, the effect of allopregnanolone on glutamate release in rat cerebrocortical nerve terminals and possible underlying mechanism were investigated. We observed that allopregnanolone inhibited 4‐aminopyridine (4‐AP)‐evoked glutamate release, and this inhibition was prevented by chelating the extracellular Ca2+ ions and the vesicular transporter inhibitor. Allopregnanolone reduced the elevation of 4‐AP‐evoked intrasynaptosomal Ca2+ levels, but did not affect the synaptosomal membrane potential. In the presence of N‐, P/Q‐, and R‐type channel blockers, allopregnanolone‐mediated inhibition of 4‐AP‐evoked glutamate release was markedly reduced; however, the intracellular Ca2+‐release inhibitors did not affect the allopregnanolone effect. Furthermore, allopregnanolone‐mediated inhibition of 4‐AP‐evoked glutamate release was completely abolished in the synaptosomes pretreated with inhibitors of Ca2+/calmodulin, adenylate cyclase, and protein kinase A (PKA), namely calmidazolium, MDL12330A, and H89, respectively. Additionally, the allopregnanolone effect on evoked glutamate release was antagonized by the GABAA receptor antagonist SR95531. Our data are the first to suggest that allopregnanolone reduce the Ca2+ influx through N‐, P/Q‐, and R‐type Ca2+ channels, through the activation of GABAA receptors present on cerebrocortical nerve terminals, subsequently suppressing the Ca2+‐calmodulin/PKA cascade and decreasing 4‐AP‐evoked glutamate release.

show abstract

GABAA receptor-mediated presynaptic inhibition on glutamatergic transmission

Cited by 29 publications

References 40 publications

Effects of Ethanol on GABA_A Receptors in GABAergic and Glutamatergic Presynaptic Nerve Terminals

Effects of Ethanol on GABA_A Receptors in GABAergic and Glutamatergic Presynaptic Nerve Terminals

Neurotoxin A2NTX Blocks Fast Inhibitory and Excitatory Transmitter Release From Presynaptic Terminals

Neurosteroid allopregnanolone inhibits glutamate release from rat cerebrocortical nerve terminals

Contact Info

Product

Resources

About

GABAA receptor-mediated presynaptic inhibition on glutamatergic transmission

Cited by 29 publications

References 40 publications

Effects of Ethanol on GABAA Receptors in GABAergic and Glutamatergic Presynaptic Nerve Terminals

Effects of Ethanol on GABAA Receptors in GABAergic and Glutamatergic Presynaptic Nerve Terminals

Neurotoxin A2NTX Blocks Fast Inhibitory and Excitatory Transmitter Release From Presynaptic Terminals

Neurosteroid allopregnanolone inhibits glutamate release from rat cerebrocortical nerve terminals

Contact Info

Product

Resources

About

Effects of Ethanol on GABA_A Receptors in GABAergic and Glutamatergic Presynaptic Nerve Terminals

Effects of Ethanol on GABA_A Receptors in GABAergic and Glutamatergic Presynaptic Nerve Terminals