Increased startle responses in mice carrying mutations of glycine receptor subunit genes

Koch, Michael; Kling, Claudia; Becker, Cord‐Michael

doi:10.1097/00001756-199602290-00030

Cited by 24 publications

(11 citation statements)

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“…The chr 11 QTL for ASR in our study (56.00-58.00 cM) is distal to the mouse gene for the glycine receptor ␣ 1 subunit (chr 11, 30.00 cM). However, a QTL for ASR on chr 3 (D3Mit199, 33.7 cM) maps closely to the mouse glycine receptor ␤ subunit gene (chr 3, 36.00 cM), mutations in which have been reported to enhance startle in mouse mutants, suggesting a role in human hyperekplexia (Koch et al 1996;Becker et al 2000).…”

Section: Discussionmentioning

confidence: 99%

Provisional Mapping of Quantitative Trait Loci Modulating the Acoustic Startle Response and Prepulse Inhibition of Acoustic Startle

Joober¹,

Zarate

Rouleau³

et al. 2002

Neuropsychopharmacology

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Prepulse inhibition (PPI) of the acoustic startle response (ASR) is a form of sensorimotor gating, defined as an inhibition of the startle response when a low intensityThere is strong evidence that several genes with additive or interactive effects, together with environmental factors, contribute to confer susceptibility to schizophrenia (Carlson and Willott 1996). Given this complexity, one approach to uncover genetic susceptibility factors in schizophrenia has been to search for genes regulating specific endophenotypes within schizophrenia. Prepulse inhibition (PPI) of the startle response is a candidate phenotype which may be relevant to such a strategy.

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Section: Discussionmentioning

confidence: 99%

Provisional Mapping of Quantitative Trait Loci Modulating the Acoustic Startle Response and Prepulse Inhibition of Acoustic Startle

Joober¹,

Zarate

Rouleau³

et al. 2002

Neuropsychopharmacology

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“…These mice not only display increased muscle tone, but also a strong hyperekplexia phenotype, very similar to epileptogenic conditions [193]. Indeed, mutations in the α1 GlyR coding gene has been found in patients with hyperekplexia/seizure disease [194].…”

Section: Mechanisms Of Ethanol Modulation On Glyrsmentioning

confidence: 99%

Ethanol effects on glycinergic transmission: From molecular pharmacology to behavior responses

Burgos

Muñoz

Guzmán

et al. 2015

Pharmacological Research

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It is well accepted that ethanol is able to produce major health and economic problems associated to its abuse. Because of its intoxicating and addictive properties, it is necessary to analyze its effect in the central nervous system. However, we are only now learning about the mechanisms controlling the modification of important membrane proteins such as ligand-activated ion channels by ethanol. Furthermore, only recently are these effects being correlated to behavioral changes. Current studies show that the glycine receptor (GlyR) is a susceptible target for low concentrations of ethanol (5 to 100 mM). GlyRs are relevant for the effects of ethanol because they are found in the spinal cord and brain stem where they primarily express the α1 subunit. More recently, the presence of GlyRs was described in higher regions, such as the hippocampus and nucleus accumbens, with a prevalence of α2/α3 subunits. Here, we review data on the following aspects of ethanol effects on GlyRs: 1) direct interaction of ethanol with amino acids in the extracellular or transmembrane domains, and indirect mechanisms through the activation of signal transduction pathways; 2) analysis of α2 and α3 subunits having different sensitivities to ethanol which allows the identification of structural requirements for ethanol modulation present in the intracellular domain and C-terminal region; 3) Genetically modified knock-in mice for α1 GlyRs that have an impaired interaction with G protein and demonstrate reduced ethanol sensitivity without changes in glycinergic transmission; and 4) GlyRs as potential therapeutic targets.

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“…Both approaches clearly indicate important roles for glycine not only in spinal motor control but also in sensory processing. Mice with inborn deficits in inhibitory glycine receptors show increased auditory startle responses (Koch et al, 1996) and are extremely sensitive to even light touch (White and Heller, 1982). Two recent studies now point to a key role of glycine in the spinal pain-controlling circuits.…”

Section: Functional Significancementioning

confidence: 99%

Glycinergic neurons expressing enhanced green fluorescent protein in bacterial artificial chromosome transgenic mice

Zeilhofer

Studler

Arabadzisz

et al. 2004

J of Comparative Neurology

324

409

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Although glycine is a major inhibitory transmitter in the mammalian CNS, the role of glycinergic neurons in defined neuronal circuits remains ill defined. This is due in part to difficulties in identifying these cells in living slice preparations for electrophysiological recordings and visualizing their axonal projections. To facilitate the morphological and functional analysis of glycinergic neurons, we generated bacterial artificial chromosome (BAC) transgenic mice, which specifically express enhanced green fluorescent protein (EGFP) under the control of the promotor of the glycine transporter (GlyT) 2 gene, which is a reliable marker for glycinergic neurons. Neurons expressing GlyT2-EGFP were intensely fluorescent, and their dendrites and axons could be visualized in great detail. Numerous positive neurons were detected in the spinal cord, brainstem, and cerebellum. The hypothalamus, intralaminar nuclei of the thalamus, and basal forebrain also received a dense GlyT2-EGFP innervation, whereas in the olfactory bulb, striatum, neocortex, hippocampus, and amygdala positive fibers were much less abundant. No GlyT2-EGFP-positive cell bodies were seen in the forebrain. On the subcellular level, GlyT2-EGFP fluorescence was colocalized extensively with glycine immunoreactivity in somata and dendrites and with both glycine and GlyT2 immunoreactivity in axon terminals, as shown by triple staining at all levels of the neuraxis, confirming the selective expression of the transgene in glycinergic neurons. In slice preparations of the spinal cord, no difference between the functional properties of EGFP-positive and negative neurons could be detected, confirming the utility of visually identifying glycinergic neurons to investigate their functional role in electrophysiological studies.

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Increased startle responses in mice carrying mutations of glycine receptor subunit genes

Cited by 24 publications

References 0 publications

Provisional Mapping of Quantitative Trait Loci Modulating the Acoustic Startle Response and Prepulse Inhibition of Acoustic Startle

Provisional Mapping of Quantitative Trait Loci Modulating the Acoustic Startle Response and Prepulse Inhibition of Acoustic Startle

Ethanol effects on glycinergic transmission: From molecular pharmacology to behavior responses

Glycinergic neurons expressing enhanced green fluorescent protein in bacterial artificial chromosome transgenic mice

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