Heterogeneity of Glycine Receptors and Their Messenger RNAs in Rat Brain and Spinal Cord

Akagi, Hiroyuki; Miledi, Ricardo

doi:10.1126/science.2845580

Cited by 124 publications

(65 citation statements)

References 15 publications

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“…A switch from neonatal ␣2-to adult ␣1-containing glycine receptors occurs during the first two postnatal weeks in the rat spinal cord (Akagi and Miledi, 1988;Becker et al, 1988;Malosio et al, 1991) and correlates with a decrease in glycine receptor mean open time and PSC decays (Takahashi et al, 1992;Singer et al, 1998). Decay parameters measured at P1-P5 were faster than those reported in neurons with predominant expression of ␣2 glycine receptors and similar to neurons at intermediate developmental stages expressing both ␣1 and ␣2 glycine receptors (Singer et al, 1998;Van Zundert et al, 2004).…”

Section: Maturation Of Postsynaptic Inhibitory Current Time Coursementioning

confidence: 40%

Differential Postnatal Maturation of GABA_A, Glycine Receptor, and Mixed Synaptic Currents in Renshaw Cells and Ventral Spinal Interneurons

González-Forero

Álvarez

2005

J. Neurosci.

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Renshaw cells (RCs) receive excitatory inputs from motoneurons to which then they inhibit. The gain of this spinal recurrent inhibitory circuit is modulated by inhibitory synapses on RCs. Inhibitory synapses on RCs mature postnatally, developing unusually large postsynaptic gephyrin clusters that colocalize glycine and GABA A receptors. We hypothesized that these features potentiate inhibitory currents in RCs. Thus, we analyzed glycinergic and GABAergic "inhibitory" miniature postsynaptic currents (mPSCs) in neonatal [postnatal day 1 (P1) to P5] and mature (P9 -P15) RCs and compared them to other ventral interneurons (non-RCs). Recorded neurons were Neurobiotin filled and identified as RCs or non-RCs using post hoc immunohistochemical criteria. Glycinergic, GABAergic, and mixed glycine/ GABA mPSCs matured differently in RCs and non-RCs. In RCs, glycinergic and GABA A mPSC peak amplitudes increased 230 and 45%, respectively, from P1-P5 to P9 -P15, whereas in non-RCs, glycinergic peak amplitudes changed little and GABA A amplitudes decreased. GABA A mPSCs were slower in RCs (P1-P5, ϭ 58 ms; P9 -P15, ϭ 43 ms) compared with non-RCs (P1-P5, ϭ 27 ms; P9 -P15, ϭ 14 ms). Thus, fast glycinergic currents dominated "mixed" mPSC peak amplitudes in mature RCs, and GABA A currents dominated their long decays. In non-RCs, GABAergic and mixed events had shorter durations, and their frequencies decreased with development. Functional maturation of inhibitory synapses on RCs correlates well with increased glycine receptor recruitment to large gephyrin patches, colocalization with ␣3/␣5-containing GABA A receptors, and maintenance of GABA/glycine corelease. As a result, charge transfer in GABA, glycine, or mixed mPSCs was larger in mature RCs than in non-RCs, suggesting RCs receive potent inhibitory synapses.

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Section: Maturation Of Postsynaptic Inhibitory Current Time Coursementioning

confidence: 40%

Differential Postnatal Maturation of GABA_A, Glycine Receptor, and Mixed Synaptic Currents in Renshaw Cells and Ventral Spinal Interneurons

González-Forero

Álvarez

2005

J. Neurosci.

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“…At low doses of Gly, the membrane current increased approximately as the 2.5th power of the Gly concentration in oocytes injected with midbrain mRNAs, and the 2.9th power in oocytes injected with brainstem mRNA. These values are not significantly different between themselves and are similar to those for GlyRs expressed by fetal human brain and rat spinal cord mRNAs (7,16), all of which suggests that at least three molecules of Gly must bind to a GlyR to gate the ion channel with a high degree of cooperativity.…”

Section: Expression Of Gly and Gaba Receptors By Embryonic Brain Mrnassupporting

confidence: 56%

“…Similarly, the amount of GlyR gene translation, assessed by the injection of developing rat cerebral cortex mRNA into Xenopus oocytes, decreases with age, whereas that of GABARs increases (6). Moreover, the type and location of mRNAs coding for GlyR changes ontogenetically (7), and the subunit composition is also changed, because the ␣2-subunit seen by in situ hybridization in embryonic day 14 (E14) midbrain is not found after E19 (8). Additionally, during development, the ␣2-subunit is replaced by the ␣1-subunit in GlyRs; and the GABA receptor ␣2͞␣3␣5␤ changes into ␣1␣4␤2␦ (9,10).…”

mentioning

confidence: 99%

Characteristics of glycine receptors expressed by embryonic rat brain mRNAs

Garcı́a-Alcocer¹,

Garcı́a-Colunga²,

Martı́nez-Torres³

et al. 2001

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

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A study was made of glycine (Gly) and ␥-aminobutyric acid (GABA) receptors expressed in Xenopus oocytes injected with rat mRNAs isolated from the encephalon, midbrain, and brainstem of 18-dayold rat embryos. In oocytes injected with encephalon, midbrain, or brainstem mRNAs, the Gly-current amplitudes (membrane current elicited by Gly; 1 mM Gly) were respectively 115 ؎ 35, 346 ؎ 28, and 389 ؎ 22 nA, whereas the GABA-currents (1 mM GABA) were all <40 nA. Moreover, the Gly-currents desensitized faster in oocytes injected with encephalon or brainstem mRNAs. The EC 50 for Gly was 611 ؎ 77 M for encephalon, 661 ؎ 28 M for midbrain, and 506 ؎ 18 M for brainstem mRNA-injected oocytes, and the corresponding Hill coefficients were all Ϸ2. Strychnine inhibited all of the Gly-currents, with an IC50 of 56 ؎ 3 nM for encephalon, 97 ؎ 4 nM for midbrain, and 72 ؎ 4 nM for brainstem mRNAs. During repetitive Gly applications, the Gly-currents were potentiated by 1.6-fold for encephalon, 2.1-fold for midbrain, and 1.3-fold for brainstem RNA-injected oocytes. Raising the extracellular Ca 2؉ concentration significantly increased the Gly-currents in oocytes injected with midbrain and brainstem mRNAs. Reverse transcription-PCR studies showed differences in the Gly receptor (GlyR) ␣-subunits expressed, whereas the ␤-subunit was present in all three types of mRNA. These results indicate differential expression of GlyR mRNAs in the brain areas examined, and these mRNAs lead to the expression of GlyRs that have different properties. The modulation of GlyRs by Ca 2؉ could play important functions during brain development.I n all vertebrates the main neurotransmitters responsible for fast inhibitory synaptic transmission are the amino acids glycine (Gly) and ␥-aminobutyric acid (GABA), which act on their specific receptors (1, 2). Molecular cloning indicates that both Gly receptors (GlyR) and GABA receptors (GABAR) have a pentameric subunit structure, arranged around a chloride-selective ion channel. The GlyR is composed of two types of glycosylated integral membrane proteins (␣1-␣4 and ␤) and an associated peripheral membrane protein (1). On the other hand, the GABAR are made up of combinations of ␣-, ␤-, ␥-, ␦-, -, -, or -subunits (3). The density, location, and subunit composition of some neurotransmitter receptors change during development. For example, mammalian fetal skeletal muscle fibers have acetylcholine receptors along their entire surface and the receptors disappear from the nonjunctional areas during development (4), and their subunit composition is also changed (5). Similarly, the amount of GlyR gene translation, assessed by the injection of developing rat cerebral cortex mRNA into Xenopus oocytes, decreases with age, whereas that of GABARs increases (6). Moreover, the type and location of mRNAs coding for GlyR changes ontogenetically (7), and the subunit composition is also changed, because the ␣2-subunit seen by in situ hybridization in embryonic day 14 (E14) midbrain is not found after E19 (8). Additionally, during developm...

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“…We next examined whether the AMPAR subunits might switch during development like other ionotropic receptors (Mishina et al, 1986;Akagi and Miledi, 1988;Becker et al, 1988;Watanabe et al, 1992;Okada et al, 2000). After recording qEPSCs from MNTB neurons, intracellular contents were harvested into the patch pipette and submitted for the quantitative RT-PCR analysis (Lambolez et al, 1992).…”

Section: Developmental Change In the Ampar Subunit Transcriptsmentioning

confidence: 99%

Mechanisms Underlying Developmental Speeding in AMPA-EPSC Decay Time at the Calyx of Held

Koike-Tani

Saitoh²,

Takahashi³

2005

J. Neurosci.

116

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The time course of synaptic conductance is important in temporal precision of information processing in the neuronal network. The AMPA receptor (AMPAR)-mediated EPSCs at the calyx of Held become faster in decay time as animals mature. To clarify how desensitization and deactivation of AMPARs contribute to developmental speeding of EPSCs, we compared the decay time of quantal EPSCs (qEPSCs) with the deactivation and desensitization times of AMPAR currents induced in excised patches by fast glutamate application (AMPA patch currents). Both the deactivation and desensitization times of AMPA patch currents became markedly faster from postnatal day 7 (P7) to P14 and changed little thereafter. In individual neurons, throughout development (P7-P21), the time constants of deactivation and fast desensitization in AMPA patch currents were similar to each other and close to the qEPSC decay time constant. Cyclothiazide (CTZ) abolished the fast desensitization, prolonged deactivation of AMPA patch currents, and slowed the decay time of EPSCs. The effects of CTZ on AMPA patch currents were unchanged throughout development, whereas its effect on EPSCs became weaker as animals matured. In single-cell reverse transcription-PCR analysis, glutamate receptor subunit 4 (GluR4) flop increased from P7 to P14 and changed little thereafter. At P7, the GluR4 flop abundance had an inverse correlation with the qEPSC decay time. These results together suggest that both desensitization and deactivation of AMPARs are involved in the EPSC decay time, but the contribution of desensitization decreases during postnatal development at the calyx of Held.

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Heterogeneity of Glycine Receptors and Their Messenger RNAs in Rat Brain and Spinal Cord

Cited by 124 publications

References 15 publications

Differential Postnatal Maturation of GABA_A, Glycine Receptor, and Mixed Synaptic Currents in Renshaw Cells and Ventral Spinal Interneurons

Differential Postnatal Maturation of GABA_A, Glycine Receptor, and Mixed Synaptic Currents in Renshaw Cells and Ventral Spinal Interneurons

Characteristics of glycine receptors expressed by embryonic rat brain mRNAs

Mechanisms Underlying Developmental Speeding in AMPA-EPSC Decay Time at the Calyx of Held

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Heterogeneity of Glycine Receptors and Their Messenger RNAs in Rat Brain and Spinal Cord

Cited by 124 publications

References 15 publications

Differential Postnatal Maturation of GABAA, Glycine Receptor, and Mixed Synaptic Currents in Renshaw Cells and Ventral Spinal Interneurons

Differential Postnatal Maturation of GABAA, Glycine Receptor, and Mixed Synaptic Currents in Renshaw Cells and Ventral Spinal Interneurons

Characteristics of glycine receptors expressed by embryonic rat brain mRNAs

Mechanisms Underlying Developmental Speeding in AMPA-EPSC Decay Time at the Calyx of Held

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Differential Postnatal Maturation of GABA_A, Glycine Receptor, and Mixed Synaptic Currents in Renshaw Cells and Ventral Spinal Interneurons

Differential Postnatal Maturation of GABA_A, Glycine Receptor, and Mixed Synaptic Currents in Renshaw Cells and Ventral Spinal Interneurons