Dynamics of GABAρ2 receptors in retinal bipolar neurons and cerebellar astrocytes

Martínez-Delgado, Gustavo; Reyes‐Haro, Daniel; Espino-Saldaña, Ángeles Edith; Rosas‐Arellano, Abraham; Pétriz, Adriana; Juárez-Mercado, Patricia; Miledi, Ricardo; Martı́nez-Torres, Ataúlfo

doi:10.1097/wnr.0b013e328340d7d6

Cited by 11 publications

(9 citation statements)

References 21 publications

(23 reference statements)

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“…***P < 0.001, one-way ANOVA. proximal processes (27). In the present study, we reexamined the distribution of this receptor subunit in astrocytes with all three morphologies and corroborated those findings.…”

Section: Gaba-a Receptors In Cerebellar Gfapsupporting

confidence: 76%

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GABAρ subunits confer a bicuculline-insensitive component to GFAP ⁺ cells of cerebellum

Pétriz

Reyes‐Haro

González-González

et al. 2014

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

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GABA-A receptors mediating synaptic or extrasynaptic transmission are molecularly and functionally distinct, and glial cells are known to express a plethora of GABA-A subunits. Here we demonstrate that GFAP + cells of the granular layer of cerebellum express GABAρ subunits during early postnatal development, thereby conferring peculiar pharmacologic characteristics to GABA responses. Electron microscopy revealed the presence of GABAρ in the plasma membrane of GFAP + cells. In contrast, expression in the adult was restricted to Purkinje neurons and a subset of ependymal cells. Electrophysiological studies in vitro revealed that astrocytes express functional receptors with an EC 50 of 52.2 ± 11.8 μM for GABA. The evoked currents were inhibited by bicuculline (100 μM) and TPMPA (IC 50 , 5.9 ± 0.6 μM), indicating the presence of a GABAρ component. Coimmunoprecipitation demonstrated protein-protein interactions between GABAρ1 and GABAα1, and double immunofluorescence showed that these subunits colocalize in the plasma membrane. Three populations of GABA-A receptors in astrocytes were identified: classic GABA-A, bicuculline-insensitive GABAρ, and GABA-A-GABAρ hybrids. Clusters of GABA-A receptors were distributed in the perinuclear space and along the processes of GFAP + cells. Time-lapse microscopy showed GABAρ2-GFP accumulation in clusters located in the soma and along the processes. The clusters were relatively immobile, with mean displacement of 9.4 ± 0.9 μm and a net distance traveled of 1-2 μm, owing mainly to directional movement or simple diffusion. Modulation of GABAρ dynamics may be a novel mechanism of extrasynaptic transmission regulating GABAergic control of GFAP + cells during early postnatal development.astrocytes | cerebellum | GABA-A receptor | GABAρ receptor | protein trafficking

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Section: Gaba-a Receptors In Cerebellar Gfapsupporting

confidence: 76%

“…Trafficking of GABAρ2 was assessed using AdGABAρ2-GFP (27), and cell morphology was highlighted using AdmCherry (6.4 × 10 …”

Section: Expression Of Fluorescent Proteins In Gfapmentioning

confidence: 99%

GABAρ subunits confer a bicuculline-insensitive component to GFAP ⁺ cells of cerebellum

Pétriz

Reyes‐Haro

González-González

et al. 2014

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

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“…1992; Müller et al. 1994; Verkhratsky and Steinhäuser 2000), whereas GABAρ2 receptors are known to be expressed in cerebellar astrocytes in culture (Martínez‐Delgado et al. 2011).…”

Section: Discussionmentioning

confidence: 99%

“…Glial cells are known to express GABA A receptors both in culture and in situ, including in Bergmann cells of the cerebellum, astrocytes of the spinal cord, optic nerve, retina, hippocampus and pituitary gland (i.e. Berger et al 1992;Müller et al 1994;Verkhratsky and Steinhäuser 2000), whereas GABAq2 receptors are known to be expressed in cerebellar astrocytes in culture (Martínez-Delgado et al 2011). Here, we report that both the GABAq1 and q2 GABA subunits are expressed in a population of GFAPpositive cells of the neostriatum; immunolabeling for GABAq was identified mainly in processes and in smaller proportion in somas.…”

Section: Discussionmentioning

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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“…We have been characterizing the expression and distribution of GABAρ subunits in the cerebellum (Mejía et al, 2008; Martínez‐Delgado et al, 2011). Because of the distinct biophysical and pharmacological properties of these GABA subunits, they might confer special functional characteristics on the cells that express them.…”

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confidence: 99%

γ‐Aminobutyric acid‐ρ expression in ependymal glial cells of the mouse cerebellum

Reyes‐Haro¹,

González-González²,

Pétriz³

et al. 2013

J of Neuroscience Research

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The ependymal glial cells (EGCs) from the periventricular zone of the cerebellum were studied to determine their distribution and the functional properties of their γ-aminobutyric acid type A (GABA(A) ) receptors. EGCs were identified by the presence of ciliated structures on their ventricular surface and their expression of glial fibrillary acidic protein (GFAP). Interestingly, diverse cell types, including neurons, astrocytes, and other types of glia, were identified in the subventricular zone by their current profiles. Electron microscopy showed ciliated cells and myelinated axons in this zone, but we found no collateral connections to suggest the presence of functional synapses. GABA-mediated currents were recorded from EGCs in cerebellar slices from postnatal days 13 to 35 (PN13-PN35). These currents were blocked by TPMPA (a highly specific GABA(A) ρ subunit antagonist) and bicuculline (a selective antagonist for classic GABA(A) receptors). Pentobarbital failed to modulate GABA(A)-mediated currents despite the expression of GABAα1 and GABAγ2 subunits. In situ hybridization, RT-PCR, and immunofluorescence studies confirmed GABAρ1 expression in EGCs of the cerebellum. We conclude that cerebellar EGCs express GABAρ1, which is functionally involved in GABA(A) receptor-mediated responses that are unique among glial cells of the brain.

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Dynamics of GABAρ2 receptors in retinal bipolar neurons and cerebellar astrocytes

Cited by 11 publications

References 21 publications

GABAρ subunits confer a bicuculline-insensitive component to GFAP ⁺ cells of cerebellum

GABAρ subunits confer a bicuculline-insensitive component to GFAP ⁺ cells of cerebellum

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

γ‐Aminobutyric acid‐ρ expression in ependymal glial cells of the mouse cerebellum

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Dynamics of GABAρ2 receptors in retinal bipolar neurons and cerebellar astrocytes

Cited by 11 publications

References 21 publications

GABAρ subunits confer a bicuculline-insensitive component to GFAP + cells of cerebellum

GABAρ subunits confer a bicuculline-insensitive component to GFAP + cells of cerebellum

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

γ‐Aminobutyric acid‐ρ expression in ependymal glial cells of the mouse cerebellum

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GABAρ subunits confer a bicuculline-insensitive component to GFAP ⁺ cells of cerebellum

GABAρ subunits confer a bicuculline-insensitive component to GFAP ⁺ cells of cerebellum