Developmental expression of the group III metabotropic glutamate receptor mGluR4a in the medial nucleus of the trapezoid body of the rat

Elezgarai, Izaskun; Benı́tez, Rocı́o; Mateos, José Marı́a; Lázaro, Esther; Osorio, Alexandra; Azkue, Jon Jatsu; Bilbao, Aurora; Lingenhoehl, Kurt; Putten, Herman van der; Hampson, David R.; Kühn, Rainer; Knöpfel, Thomas; Grandes, Pedro

doi:10.1002/(sici)1096-9861(19990830)411:3<431::aid-cne6>3.0.co;2-r

Cited by 40 publications

(31 citation statements)

References 52 publications

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“…It has previously been reported that G i (but not G o ) activates the G protein-activated inwardly rectifying potassium current (GIRK) (32 An involvement of a phospholipase C-dependent pathway has been suggested for the inhibition of P͞Q-type Ca 2ϩ currents by mGluR7 in cerebellar granule cell soma (33). The calyx of Held terminal expresses mGluR4 and also mGluR7 at later stages of development (34), and presynaptic inhibition by an mGluR agonist is mediated by inhibition of presynaptic P͞Q-type Ca 2ϩ currents (2). This effect of mGluR agonist can be completely occluded by baclofen (Y.K.…”

Section: Discussionmentioning

confidence: 99%

GTP-binding protein βγ subunits mediate presynaptic calcium current inhibition by GABA _B receptor

Kajikawa

Saitoh

Takahashi

2001

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

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A variety of GTP-binding protein (G protein)-coupled receptors are expressed at the nerve terminals of central synapses and play modulatory roles in transmitter release. At the calyx of Held, a rat auditory brainstem synapse, activation of presynaptic ␥-aminobutyric acid type B receptors (GABAB receptors) or metabotropic glutamate receptors inhibits presynaptic P͞Q-type Ca 2؉ channel currents via activation of G proteins, thereby attenuating transmitter release. To identify the heterotrimeric G protein subunits involved in this presynaptic inhibition, we loaded G protein ␤␥ subunits (G␤␥) directly into the calyceal nerve terminal through whole-cell patch pipettes. G␤␥ slowed the activation of presynaptic Ca 2؉ currents (IpCa) and attenuated its amplitude in a manner similar to the externally applied baclofen, a GABAB receptor agonist. The effects of both G␤␥ and baclofen were relieved after strong depolarization of the nerve terminal. In addition, G␤␥ partially occluded the inhibitory effect of baclofen on IpCa. In contrast, guanosine 5 -O-(3-thiotriphosphate)-bound Go␣ loaded into the calyx had no effect. Immunocytochemical examination revealed that the subtype of G proteins Go, but not the Gi, subtype, is expressed in the calyceal nerve terminal. These results suggest that presynaptic inhibition mediated by G protein-coupled receptors occurs primarily by means of the direct interaction of Go ␤␥ subunits with presynaptic Ca 2؉ channels.I n the central nervous system, synaptic transmission is regulated by presynaptic autoreceptors or heteroreceptors. These receptors are coupled by G proteins to various targets such as Ca 2ϩ channels, K ϩ channels, or the exocytotic machinery downstream of Ca 2ϩ influx (1). At a rat brainstem auditory synapse formed by a giant nerve terminal, the calyx of Held, metabotropic glutamate receptors (mGluRs), or ␥-aminobutyric acid type B receptors (GABA B receptors) primarily inhibit P͞Q-type Ca 2ϩ channels (2-4). The inhibitory effect of the GABA B receptor agonist baclofen on presynaptic Ca 2ϩ currents can be blocked by the GDP analog guanosine 5Ј-O-(2-thiodiphosphate) (GDP [␤S]) and occluded by the nonhydrolyzable GTP analog guanosine 5Ј-O-(3-thiotriphosphate) (GTP[␥S]), both loaded directly into the calyx, indicating that G proteins mediate the presynaptic inhibition (3). At the cell soma, heterotrimeric G proteins attenuate Ca 2ϩ currents acting either directly via a membrane-delimited pathway involving G protein ␤␥ subunits (G␤␥) or indirectly via second messengers (5, 6). At the nerve terminal, however, it is not known which mechanism underlies this presynaptic inhibition. At the calyx of Held, which can be visually identified in slice, it is possible to load various molecules into the nerve terminal through whole-cell recording pipette (3,7,8). Using this technique, we examined the effect of G␤␥ on I pCa . Also, because of its large structure, it was possible to use immunocytochemistry to determine the subtype of G proteins expressed in the calyceal nerve terminal. Our results...

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Section: Discussionmentioning

confidence: 99%

GTP-binding protein βγ subunits mediate presynaptic calcium current inhibition by GABA _B receptor

Kajikawa

Saitoh

Takahashi

2001

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

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“…1D) (Takahashi et al, 1996;Kushmerick et al, 2004). Metabotropic GluRs have been localized synaptically and extrasynaptically in the calyx terminal (Elezgarai et al, 1999(Elezgarai et al, , 2001. To test whether released glutamate is able to escape the synaptic cleft and activate extrasynaptic GluRs, we recorded from pairs of calyx terminals and neighboring principal MNTB neurons ( Fig.…”

Section: Inactivation Of Presynaptic Voltage-gated Camentioning

confidence: 99%

Similar Intracellular Ca²⁺Requirements for Inactivation and Facilitation of Voltage-Gated Ca²⁺Channels in a Glutamatergic Mammalian Nerve Terminal

Lin

Erazo-Fischer²,

Taschenberger

2012

J. Neurosci.

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“…At this age, the calyx of Held has acquired an adult-like morphology and rat pups respond to sound stimuli. Thus, unlike some group III mGluR subtypes that disappear during early development (Elezgarai et al, 1999), the mGluR1a-CB1R signaling pathway may be relevant for hearing animals and not only during early development. Group I mGluRs may also have a neuroprotective role in setting physiological [Ca 2ϩ ] i levels (Zirpel and Rubel, 1996;Zirpel et al, 2000).…”

Section: Group I Mglur Modulation Of the Mntb Outputmentioning

confidence: 99%

“…The calyx of Held, a glutamatergic nerve terminal located in the medial nucleus of the trapezoid body (MNTB), permits direct recording of presynaptic APs and Ca 2ϩ currents (Forsythe, 1994;Borst and Sakmann, 1998). This synapse expresses presynaptic group II and III mGluRs that are negatively coupled to neurotransmitter release (Barnes-Davies and Forsythe, 1995;von Gersdorff et al, 1997;Elezgarai et al, 1999Elezgarai et al, , 2001. In contrast, the expression and function of group I mGluRs and CB1Rs at the calyx of Held have not been explored.…”

Section: Introductionmentioning

confidence: 99%

Retroinhibition of Presynaptic Ca²⁺Currents by Endocannabinoids Released via Postsynaptic mGluR Activation at a Calyx Synapse

Kushmerick¹,

Price²,

et al. 2004

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Developmental expression of the group III metabotropic glutamate receptor mGluR4a in the medial nucleus of the trapezoid body of the rat

Cited by 40 publications

References 52 publications

GTP-binding protein βγ subunits mediate presynaptic calcium current inhibition by GABA _B receptor

GTP-binding protein βγ subunits mediate presynaptic calcium current inhibition by GABA _B receptor

Similar Intracellular Ca²⁺Requirements for Inactivation and Facilitation of Voltage-Gated Ca²⁺Channels in a Glutamatergic Mammalian Nerve Terminal

Retroinhibition of Presynaptic Ca²⁺Currents by Endocannabinoids Released via Postsynaptic mGluR Activation at a Calyx Synapse

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Developmental expression of the group III metabotropic glutamate receptor mGluR4a in the medial nucleus of the trapezoid body of the rat

Cited by 40 publications

References 52 publications

GTP-binding protein βγ subunits mediate presynaptic calcium current inhibition by GABA B receptor

GTP-binding protein βγ subunits mediate presynaptic calcium current inhibition by GABA B receptor

Similar Intracellular Ca2+Requirements for Inactivation and Facilitation of Voltage-Gated Ca2+Channels in a Glutamatergic Mammalian Nerve Terminal

Retroinhibition of Presynaptic Ca2+Currents by Endocannabinoids Released via Postsynaptic mGluR Activation at a Calyx Synapse

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Product

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GTP-binding protein βγ subunits mediate presynaptic calcium current inhibition by GABA _B receptor

GTP-binding protein βγ subunits mediate presynaptic calcium current inhibition by GABA _B receptor

Similar Intracellular Ca²⁺Requirements for Inactivation and Facilitation of Voltage-Gated Ca²⁺Channels in a Glutamatergic Mammalian Nerve Terminal

Retroinhibition of Presynaptic Ca²⁺Currents by Endocannabinoids Released via Postsynaptic mGluR Activation at a Calyx Synapse