GABA Is Dispensable for the Formation of Junctional GABA Receptor Clusters in<i>Caenorhabditis elegans</i>

Gally, Christelle; Bessereau, Jean-Louis

doi:10.1523/jneurosci.23-07-02591.2003

Cited by 78 publications

(69 citation statements)

References 62 publications

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“…The results described by Jiang et al (2005) strongly imply that the recycling function is more critical for GABAergic neurotransmission in C. elegans because snf-11 RNAi results in a GABAergic "loss-of-function" phenotype. Alternatively, Jiang et al (2005) suggest that GABA receptors have been down-regulated; however, other studies fail to support this view (Gally and Bessereau, 2003). In contrast, our results clearly indicate that the GABA transporter in C. elegans functions chiefly in the clearance of GABA.…”

Section: Discrepancies With a Previous Study On Snf-11contrasting

confidence: 77%

TheCaenorhabditis elegans snf-11Gene Encodes a Sodium-dependent GABA Transporter Required for Clearance of Synaptic GABA

Mullen

Mathews

Saxena

et al. 2006

MBoC

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Sodium-dependent neurotransmitter transporters participate in the clearance and/or recycling of neurotransmitters from synaptic clefts. The snf-11 gene in Caenorhabditis elegans encodes a protein of high similarity to mammalian GABA transporters (GATs). We show here that snf-11 encodes a functional GABA transporter; SNF-11-mediated GABA transport is Na ؉ and Cl ؊ dependent, has an EC 50 value of 168 M, and is blocked by the GAT1 inhibitor SKF89976A. The SNF-11 protein is expressed in seven GABAergic neurons, several additional neurons in the head and retrovesicular ganglion, and three groups of muscle cells. Therefore, all GABAergic synapses are associated with either presynaptic or postsynaptic (or both) expression of SNF-11. Although a snf-11 null mutation has no obvious effects on GABAergic behaviors, it leads to resistance to inhibitors of acetylcholinesterase. In vivo, a snf-11 null mutation blocks GABA uptake in at least a subset of GABAergic cells; in a cell culture system, all GABA uptake is abolished by the snf-11 mutation. We conclude that GABA transport activity is not essential for normal GABAergic function in C. elegans and that the localization of SNF-11 is consistent with a GABA clearance function rather than recycling.

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Section: Discrepancies With a Previous Study On Snf-11contrasting

confidence: 77%

TheCaenorhabditis elegans snf-11Gene Encodes a Sodium-dependent GABA Transporter Required for Clearance of Synaptic GABA

Mullen

Mathews

Saxena

et al. 2006

MBoC

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“…Altogether, these observations confirm that neurotransmitter-mediated activity is not essential for synapse formation (91)(92)(93)(94) and indicate that differential mechanisms ensure long-term stability of synapses in various cell compartments. While the normal morphology and content of presynaptic vesicles of basket cell terminals suggest that these terminals remain competent for GABA synthesis and release, activation of postsynaptic GABA A receptors is not required for maintenance of this synapse.…”

Section: Requirement Of Gaba a Receptors For Longterm Maintenance Of supporting

confidence: 60%

Molecular and synaptic organization of GABAA receptors in the cerebellum: Effects of targeted subunit gene deletions

Fritschy

Panzanelli

2006

Cerebellum

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GABA A receptors form heteromeric GABA-gated chloride channels assembled from a large family of subunit genes. In cerebellum, distinct GABA A receptor subtypes, differing in subunit composition, are segregated between cell types and synaptic circuits. The cerebellum therefore represents a useful system to investigate the significance of GABA A receptor heterogeneity. For instance, studies of mice carrying targeted deletion of major GABA A receptor subunit genes revealed the role of a subunit variants for receptor assembly, synaptic targeting, and functional properties. In addition, these studies unraveled mandatory association between certain subunits and demonstrated distinct pharmacology of receptors mediating phasic and tonic inhibition. Although some of these mutants have a profound loss of GABA A receptors, they exhibit only minor impairment of motor function, suggesting activation of compensatory mechanisms to preserve inhibitory networks in the cerebellum. These adaptations include an altered balance between phasic and tonic inhibition, activation of voltageindependent K + conductances, and upregulation of GABA A receptors in interneurons that are not affected directly by the mutation. Deletion of the a1 subunit gene leads to complete loss of GABA A receptors in Purkinje cells. A striking alteration occurs in these mice, whereby presynaptic GABAergic terminals are preserved in the molecular layer but make heterologous synapses with spines, characterized by a glutamatergic-like postsynaptic density. During development of a1 0/0 mice, GABAergic synapses are initially formed but are replaced upon spine maturation. These findings suggest that functional GABA A receptors are required for long-term maintenance of GABAergic synapses in Purkinje cells.

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“…At the light level, fluorescently tagged synaptic vesicles appeared to cluster normally in GABA neurons [15]. The postsynaptic inhibitory GABA receptor also appeared to have a normal distribution in unc-25 mutants [18]. A reconstruction of the ventral nerve cord from serial electron micrographs demonstrated that the synaptic structure and connectivity were correct [15].…”

Section: Unc-25: Is Gaba Required For Development?mentioning

confidence: 95%

The GABA nervous system in C. elegans

Schuske

Beg

Jørgensen

2004

Trends in Neurosciences

164

151

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GABA neurotransmission requires a specialized set of proteins to synthesize, transport or respond to GABA. This article reviews results from a genetic strategy in the nematode Caenorhabditis elegans designed to identify the genes responsible for these activities. These studies identified mutations in genes encoding five different proteins: the biosynthetic enzyme for GABA, the vesicular GABA transporter, a transcription factor that determines GABA neuron identity, a classic inhibitory GABA receptor and a novel excitatory GABA receptor. This review discusses the strategy employed to identify these genes as well as the conclusions about GABA transmission derived from study of the mutant phenotypes.Activity in the vertebrate brain depends on a yin and yang balance between excitatory and inhibitory neurotransmission. A deficit of excitatory neurotransmission will lead to unconsciousness; a deficit of inhibitory neurotransmission will lead to epileptic seizures. The most abundant inhibitory neurotransmitter in the brain is GABA. Normal GABA function requires specialized proteins such as biosynthetic enzymes, transporters and receptors. Defects in these proteins can lead to a specific imbalance of GABA neurotransmission and lead to diseases. For example, mutations in the a1 and g2 GABA receptor subunits can cause familial forms of epilepsy [1 -3].Over ten years ago, a strategy was devised to identify the proteins specialized for GABA function using a genetic approach in the nematode Caenorhabditis elegans [4,5]. These studies have lead to some important discoveries. Specifically, the vesicular GABA transporter (VGAT) was first discovered in C. elegans and this sequence was used to identify the mammalian homolog [6]. The homeodomain protein UNC-30 identified a class of transcription factors required for multiple aspects of GABA neuron identity [7,8]. These studies also revealed the first cation-selective GABA receptor [9]. This review will discuss first the strategy used to identify proteins required for GABA neurotransmission in C. elegans and then the impact that their discovery has had on our understanding of GABA function. StrategyTo define the proteins required for GABA function, McIntire and colleagues looked for mutations in the nematode C. elegans that specifically disrupted GABAmediated behaviors [4,5]. To identify the GABA-containing cells in C. elegans, animals were stained using antibodies against the neurotransmitter. Antibody staining revealed that 26 of the 302 neurons present in C. elegans express the neurotransmitter GABA (Figure 1a). These 26 GABApositive neurons comprise six DD neurons, 13 VD neurons, four RME neurons, an RIS neuron, an AVL neuron and a DVB neuron (Figure 1b). These neurons fall into different classes based on their synaptic outputs: the D-type neurons -that is, the DD and VD motor neuronsinnervate the dorsal and ventral body muscles, respectively; the RME motor neurons innervate the head muscles; the AVL and DVB motor neurons innervate the enteric muscles; and RIS is an interneuron ...

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GABA Is Dispensable for the Formation of Junctional GABA Receptor Clusters inCaenorhabditis elegans

Cited by 78 publications

References 62 publications

TheCaenorhabditis elegans snf-11Gene Encodes a Sodium-dependent GABA Transporter Required for Clearance of Synaptic GABA

TheCaenorhabditis elegans snf-11Gene Encodes a Sodium-dependent GABA Transporter Required for Clearance of Synaptic GABA

Molecular and synaptic organization of GABAA receptors in the cerebellum: Effects of targeted subunit gene deletions

The GABA nervous system in C. elegans

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