GABAC receptors are expressed in GABAergic and non-GABAergic neurons of the rat superior colliculus and visual cortex

Grabert, Jochen; Jost, B.; Möllmann, Michael; Patz, Silke; Schmidt, Matthias; Wahle, Petra

doi:10.1007/s00221-009-1710-z

Cited by 6 publications

(7 citation statements)

References 37 publications

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“…The superfical layers of the mammalian superior colliculus (SC) are involved in processing the visual information, and it is precisely in this area that GABAρ receptors are expressed [ 14 , 120 , 121 ]. GABAergic interneurons in the striatum gray superficiale (SGS) and pretectal nuclear complex (PNC) have been found to express the receptor and GABA transporter 1 (GAT 1) [ 102 , 122 - 124 ].…”

Section: Distribution In the Cns And Beyondmentioning

confidence: 99%

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An Update on GABAρ Receptors

Martínez-Delgado¹,

Estrada-Mondragón²,

Miledi³

et al. 2010

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The present review discusses the functional and molecular diversity of GABAρ receptors. These receptors were originally described in the mammalian retina, and their functional role in the visual pathway has been recently elucidated; however new studies on their distribution in the brain and spinal cord have revealed that they are more spread than originally thought, and thus it will be important to determine their physiological contribution to the GABAergic transmission in other areas of the central nervous system. In addition, molecular modeling has revealed peculiar traits of these receptors that have impacted on the interpretations of the latest pharmacolgical and biophysical findings. Finally, sequencing of several vertebrate genomes has permitted a comparative analysis of the organization of the GABAρ genes.

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Section: Distribution In the Cns And Beyondmentioning

confidence: 99%

“…In the visual cortex, only the GABAρ2 subunit mRNA is expressed [ 102 ]. Finally, it has also been shown by in situ hybridization that GABAρ1 and GABAρ2 are expressed in the Stratum opticum [ 121 ], optic nerve tract [ 99 ], and superficial gray layer [ 130 ].…”

Section: Distribution In the Cns And Beyondmentioning

confidence: 99%

An Update on GABAρ Receptors

Martínez-Delgado¹,

Estrada-Mondragón²,

Miledi³

et al. 2010

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“…GABA A receptors containing the ρ subunit are predominantly expressed in the retina where knockout of the ρ1 subunit eliminates GABA-evoked responses in rod bipolar cells (McCall et al 2002). Additionally, ρ subunits are expressed in the hippocampus (Alakuijala et al 2005; Didelon et al 2002), superior colliculus (Schlicker et al 2009; Wahle and Schmidt 2009), visual cortex (Wahle and Schmidt 2009), cerebellum (Rozzo et al 2002; Wegelius et al 1998), and dorsal root ganglia (Wegelius et al 1998). The physiological and pharmacological properties of ρ receptors differ in some aspects from the more common αβγ and αβδ subtypes of the GABA A receptor.…”

Section: Introductionmentioning

confidence: 99%

Modulation of the human ρ1 GABAA receptor by inhibitory steroids

2013

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Rationale Modulators of the ρ1 GABAA receptor may be useful in the treatment of visual, sleep, and cognitive disorders. Neuroactive steroids and analogues have been shown to modulate ρ1 receptor function but the molecular mechanisms are poorly understood. Objectives We employed electrophysiology and voltage-clamp fluorometry to compare the actions of several neuroactive steroids and analogues on the human ρ1 GABAA receptor. Results Results confirmed that P294S and T298F mutations affect modulation by steroids. The P294S mutation abolished inhibition by (3α,5β)-3-hydroxypregnan-20-one (3α5βP) while the T298F mutation eliminated inhibition by 17β-estradiol. Voltage-clamp fluorometry demonstrated that steroids differing in the presence of a charged group on C3 or nature of substituent on C17 uniquely modified fluorescence changes elicited by GABA in the extracellular domain. The I307Q mutation reversed the inhibitory effect of 3α5βP but was without effect on modulation by (3α,5β)-3-hydroxypregnan-20-one sulfate or 17β-estradiol. The effect of 3α5βP on the fluorescence change generated at Y241C was dependent on whether the steroid acted as an inhibitor or a potentiator. Further, the effect was limited to uncharged 5β-reduced steroids containing an acetyl group on C17. Conclusions The data demonstrate that steroids and analogues differ with respect to conformational changes elicited by these drugs as well as sensitivity to the effects of mutations. Steroids and analogues could be provisionally divided into three major groups based on their actions on the ρ1 GABAA receptor: 5β-reduced uncharged steroids, sulfated and carboxylated steroids, and 17β-estradiol. Further division among 5β-reduced uncharged steroids was based on substituent at position C17.

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“…2001; Frazao et al. 2007; Born and Schmidt 2008; Wahle and Schmidt 2009), in the oval and pyramidal neurons of layers II‐VI of the visual cortex (Wegelius et al. 1998; Wahle and Schmidt 2009; Rosas‐Arellano et al.…”

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confidence: 99%

“…Despite the accumulated knowledge about GABAq receptors their specific function in the central nervous system remains largely unknown. These receptors have been located in the amygdala (Delaney and Sah 1999;Fujimura et al 2005;Flores-Gracia et al 2010;Rosas-Arellano et al 2011), in the mitral layer of the olfactory bulb (Chen et al 2007), Purkinje neurons of cerebellum (Drew and Johnston 1992;Albrecht et al 1997;Boue-Grabot et al 1998;Rozzo et al 2002;Harvey et al 2006;Mejía et al 2008;); in the gray layer of the superior colliculus (Wegelius et al 1998;Pasternack et al 1999;Schmidt et al 2001;Frazao et al 2007;Born and Schmidt 2008;Wahle and Schmidt 2009), in the oval and pyramidal neurons of layers II-VI of the visual cortex (Wegelius et al 1998;Wahle and Schmidt 2009;Rosas-Arellano et al 2011); in the corpus callosum (López-Chávez et al 2005); in brainstem and spinal cord (Johnston et al 1975;Wegelius et al 1998;Rozzo et al 2002;Zheng et al 2003;Milligan et al 2004;López-Chávez et al 2005;Frazao et al 2007;Rosas-Arellano et al 2007). In addition, several reports indicate that the pyramidal neurons of CA1-CA3 areas, dentate gyrus, and subiculum of the hippocampus express GABAq receptors (Strata and Cherubini 1994;Cherubini et al 1998;Wegelius et al 1998;Didelon et al 2002;…”

mentioning

confidence: 99%

Expression of GABAρ receptors in the neostriatum: localization in aspiny, medium spiny neurons and GFAP‐positive cells

Rosas‐Arellano

Machuca-Parra

Reyes‐Haro

et al. 2012

Journal of Neurochemistry

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J. Neurochem. (2012) 122, 900–910. Abstract GABAergic transmission in the neostriatum plays a central role in motor coordination, in which a plethora of GABA‐A receptor subunits combine to modulate neural inhibition. GABAρ receptors were originally described in the mammalian retina. These receptors possess special electrophysiological and pharmacological properties, forming a characteristic class of ionotropic receptors. In previous studies, we suggested that GABAρ receptors are expressed in the neostriatum, and in this report we show that they are indeed present in all the calretinin‐positive interneurons of the neostriatum. In addition, they are located in calbindin‐positive interneurons and projection neurons that express the dopamine D2 receptor. GABAρ receptors were also located in 30% of the glial fibrillary acidic protein‐positive cells, and may therefore also contribute to gliotransmission. Quantitative reverse transcription‐PCR suggested that the mRNAs of this receptor do not express as much as in the retina, and that GABAρ2 is more abundant than GABAρ1. Electrophysiological recordings in brain slices provided evidence of neurons expressing a cis‐4‐aminocrotonic acid‐activated, 1,2,5,6‐tetrahydropyridine‐4‐yl methylphosphinic acid‐sensitive ionotropic GABA receptor, indicating the presence of functional GABAρ receptors in the neostriatum. Finally, electron‐microscopy and immunogold located the receptors mainly in perisynaptic as well as in extrasynaptic sites. All these observations reinforce the importance of GABAρ receptors in the neostriatum and contribute to the diversity of inhibitory regulation in this area.

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GABAC receptors are expressed in GABAergic and non-GABAergic neurons of the rat superior colliculus and visual cortex

Cited by 6 publications

References 37 publications

An Update on GABAρ Receptors

An Update on GABAρ Receptors

Modulation of the human ρ1 GABAA receptor by inhibitory steroids

Expression of GABAρ receptors in the neostriatum: localization in aspiny, medium spiny neurons and GFAP‐positive cells

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GABAC receptors are expressed in GABAergic and non-GABAergic neurons of the rat superior colliculus and visual cortex

Cited by 6 publications

References 37 publications

An Update on GABA&#x3c1; Receptors

An Update on GABA&#x3c1; Receptors

Modulation of the human ρ1 GABAA receptor by inhibitory steroids

Expression of GABAρ receptors in the neostriatum: localization in aspiny, medium spiny neurons and GFAP‐positive cells

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An Update on GABAρ Receptors

An Update on GABAρ Receptors