Differential Distribution of Glycine Receptor Subtypes at the Rat Calyx of Held Synapse

Hruskova, Bohdana; Trojanova, Johana; Kulik, Ákos; Králíková, Michaela; Pysanenko, Kateryna; Bureš, Zbyněk; Syka, Josef; Trussell, Laurence O.; Tureček, Rostislav

doi:10.1523/jneurosci.1547-12.2012

Cited by 24 publications

(35 citation statements)

References 103 publications

(153 reference statements)

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“…In line with a previous report (31), we found tonic currents only in a small portion of cells, and these currents were of very small (≤5 pA) amplitudes. In certain areas of the brainstem, homomeric α1GlyRs have been reported to be present in presynaptic terminals where they control transmitter release (47,48). The lack of modulation of glycinergic synaptic currents by 2,6-DTBP suggests that such homomeric presynaptic GlyRs are not present in the superficial dorsal horn.…”

Section: Methodsmentioning

confidence: 99%

Phosphorylation state–dependent modulation of spinal glycine receptors alleviates inflammatory pain

Acuña¹,

Yévenes²,

Ralvenius³

et al. 2016

Journal of Clinical Investigation

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Section: Methodsmentioning

confidence: 99%

Phosphorylation state–dependent modulation of spinal glycine receptors alleviates inflammatory pain

Acuña¹,

Yévenes²,

Ralvenius³

et al. 2016

Journal of Clinical Investigation

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“…Note that these areas of juxtaposed label can be larger or smaller. The two white arrows near the left border of the image mark two large juxtaposed clusters that appear to consist of several smaller GlyT2/gephyrin clusters (Hruskova et al 2012), while the arrowheads near the bottom and the right side of the image mark smaller clusters.…”

Section: Number Of Glycinergic Synapses Observed On Mntb Neuronsmentioning

confidence: 99%

Glycinergic inhibition to the medial nucleus of the trapezoid body shows prominent facilitation and can sustain high levels of ongoing activity

Mayer

Albrecht

Dondzillo

et al. 2014

Journal of Neurophysiology

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tion to the medial nucleus of the trapezoid body shows prominent facilitation and can sustain high levels of ongoing activity. J Neurophysiol 112: 2901-2915. First published September 3, 2014 doi:10.1152/jn.00864.2013.-Neurons in the medial nucleus of the trapezoid body (MNTB) are well known for their prominent excitatory inputs, mediated by the calyx of Held. Less attention has been paid to the prominent inhibitory inputs that MNTB neurons also receive. Because of their auditory nature, both excitatory and inhibitory synapses are highly active in vivo. These high levels of activity are known to reduce excitatory synaptic currents considerably, such that in vivo synaptic currents produced by the calyx are smaller than typically measured in standard brain slice experiments. The goal of this study was to investigate the properties of the inhibitory inputs in the Mongolian gerbil (Meriones unguiculatus) under activity levels that correspond to those in the intact brain to facilitate a direct comparison between the two inputs. Our results suggest that inhibitory inputs to MNTB are largely mediated by a fast and phasic glycinergic component, and to a lesser degree by a GABAergic component. The glycinergic component can sustain prolonged high levels of activity. Even when challenged with stimulus patterns consisting of thousands of stimuli over tens of minutes, glycinergic inputs to MNTB maintain large conductances and fast decays and even facilitate substantially when the stimulation frequency is increased. The inhibition is mediated by a relatively small number of independent input fibers. The data presented here suggest that inhibitory inputs to MNTB sustain high levels of activity and need to be considered for a full understanding of mechanisms underlying processing of auditory information in MNTB. auditory brain stem; inhibition; medial nucleus of the trapezoid body; calyx of Held; short-term plasticity SYNAPTIC TRANSMISSION in the medial nucleus of the trapezoid body (MNTB) has been studied extensively over the last years. Principal neurons in the MNTB receive neural excitation via a giant synapse, the calyx of Held (Borst et al. 1995;Borst and Soria van Hoeve 2012;Forsythe 1994;Held 1892Held , 1893Tolbert et al. 1982). Synaptic currents produced by the calyx are large and fast, and both the calyx and the postsynaptic neuron have a number of adaptations suited to transmit action potentials with very high temporal fidelity (Guinan and Li 1990;Kochubey et al. 2009;Taschenberger and von Gersdorff 2000). Besides temporal precision, it has been argued that one reason for the large excitatory signals is that the calyx of Held/MNTB system is a fail-safe relay station that simply converts glutamatergic excitation into glycinergic inhibition without any significant spike train transformation (Borst and Soria van Hoeve 2012;Crins et al. 2011;McLaughlin et al. 2008;Smith et al. 1998;Taschenberger and von Gersdorff 2000). The sign inversion is needed because neural inhibition is required in the sound localization process i...

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“…Low concentrations of PTX have been shown to preferentially inhibit homomeric α GlyRs without significantly altering heteromeric αβ GlyRs expressed in HEK-293 cells 21, 22 . Similarly, PTX at low doses is also found to selectively affect presynaptic GlyRs, which are likely homomers, in the spinal cord and brainstem 7, 9, 23 . We first examined the sensitivity of homomeric and heteromeric α1R271Q mutant GlyRs to PTX-induced inhibition when expressed in HEK-293 cells.…”

Section: Resultsmentioning

confidence: 93%

“…The Calyx of Held and its postsynaptic target, medial nucleus of the trapezoid body (MNTB), function as a critical relay in brainstem auditory circuitry. Moreover, these calyceal terminals seem to be an ideal preparation for us to study homomeric α1 subunits because of lacking the β, α2 and α3 GlyR subunits 9 . We next recorded using whole-cell patch-clamp from both I Gly presynaptic and postsynaptic terminals in Calyx of Held neurons from postnatal (P) 12-P18 mice (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Different from postsynaptic heteromeric GlyRs, presynaptic GlyRs are likely formed by homomeric α subunits 7, 8 . A recent study has characterized the anatomical segregation of presynaptic and postsynaptic GlyRs in detail in calyx of held neurons from auditory brainstem 9 . This study has provided strong evidence to show that the GlyRs at presynaptic terminals of calycreal synapses are composed of homomeric α1 subunits.…”

Section: Introductionmentioning

confidence: 99%

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Presynaptic glycine receptors as a potential therapeutic target for hyperekplexia disease

Xiong

Chen

et al. 2014

Nat Neurosci

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While postsynaptic GlyRs as α/β heteromers attract the most research attention, little is known about the role of presynaptic GlyRs, likely α homomers, in diseases. Here, we demonstrate that DH-CBD, a nonpsychoactive cannabinoid, can rescue GlyR functional deficiency and exaggerated acoustic and tactile startle responses in mice bearing the point-mutations in the α1 GlyRs responsible for a hereditary startle/hyperekplexia disease. The GlyRs expressed as α1 homomers either in HEK-293 cells or at presynaptic terminals of the calyceal synapses in auditory brainstem are most vulnerable to hyperekplexia mutation-induced impairment. Homomeric mutants are more sensitive than heteromers to DH-CBD, suggesting presynaptic GlyRs as a primary target. Consistent with this, DH-CBD selectively rescues impaired presynaptic GlyR activity and diminished glycine release in the brainstem and spinal cord of hyperekplexic mutant mice. Thus, presynaptic α GlyRs emerge as a potential therapeutic target for dominant hyperekplexia disease and other diseases with GlyR deficiency.

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Differential Distribution of Glycine Receptor Subtypes at the Rat Calyx of Held Synapse

Cited by 24 publications

References 103 publications

Phosphorylation state–dependent modulation of spinal glycine receptors alleviates inflammatory pain

Phosphorylation state–dependent modulation of spinal glycine receptors alleviates inflammatory pain

Glycinergic inhibition to the medial nucleus of the trapezoid body shows prominent facilitation and can sustain high levels of ongoing activity

Presynaptic glycine receptors as a potential therapeutic target for hyperekplexia disease

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