ACR-12 Ionotropic Acetylcholine Receptor Complexes Regulate Inhibitory Motor Neuron Activity in<i>Caenorhabditis elegans</i>

Petrash, Hilary A.; Philbrook, Alison; Haburčák, Marián; Barbagallo, Belinda; Francis, Michael M.

doi:10.1523/jneurosci.4384-12.2013

Cited by 54 publications

(62 citation statements)

References 35 publications

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“…2 DD neurons receive cholinergic synaptic inputs, and express acetylcholine receptor subunits, including ACR-12, 16 in their dendrites. In L1 DD neurons, OIG-1 prevents remodeling of ACR-12.…”

Section: Factors That Regulate the Timing Of Dd Remodelingmentioning

confidence: 99%

Neural circuit rewiring: insights from DD synapse remodeling

Kurup

Jin

2015

Worm

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Nervous systems exhibit many forms of neuronal plasticity during growth, learning and memory consolidation, as well as in response to injury. Such plasticity can occur across entire nervous systems as with the case of insect metamorphosis, in individual classes of neurons, or even at the level of a single neuron. A striking example of neuronal plasticity in C. elegans is the synaptic rewiring of the GABAergic Dorsal D-type motor neurons during larval development, termed DD remodeling. DD remodeling entails multi-step coordination to concurrently eliminate pre-existing synapses and form new synapses on different neurites, without changing the overall morphology of the neuron. This mini-review focuses on recent advances in understanding the cellular and molecular mechanisms driving DD remodeling.

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Section: Factors That Regulate the Timing Of Dd Remodelingmentioning

confidence: 99%

Neural circuit rewiring: insights from DD synapse remodeling

Kurup

Jin

2015

Worm

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“…The nicotinic AChR subunit ACR-12 is a constituent of GABA neuron iAChRs. ACR-12::GFP clusters localize opposite ACh release sites and relocate appropriately during developmental remodeling, suggesting that these clusters report mature postsynaptic structures (Petrash et al, 2013;He et al, 2015). We examined the distribution of ACR-12:: GFP in the dorsal nerve cord where the majority of chemical synaptic inputs to VD neurons occur (VD synaptic contacts with muscles are exclusively ventral) (White et al, 1986).…”

Section: Unc-3 Transcriptional Regulation Coordinates Cholinergic Synmentioning

confidence: 99%

Excitatory neurons sculpt GABAergic neuronal connectivity in the C. elegans motor circuit

et al. 2017

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Establishing and maintaining the appropriate number of GABA synapses is key for balancing excitation and inhibition in the nervous system, though we have only a limited understanding of the mechanisms controlling GABA circuit connectivity. Here, we show that disrupting cholinergic innervation of GABAergic neurons in the C. elegans motor circuit alters GABAergic neuron synaptic connectivity. These changes are accompanied by reduced frequency and increased amplitude of GABAergic synaptic events. Acute genetic disruption in early development, during the integration of postembryonic-born GABAergic neurons into the circuit, produces irreversible effects on GABAergic synaptic connectivity that mimic those produced by chronic manipulations. In contrast, acute genetic disruption of cholinergic signaling in the adult circuit does not reproduce these effects. Our findings reveal that GABAergic signaling is regulated by cholinergic neuronal activity, probably through distinct mechanisms in the developing and mature nervous system.

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“…Our finding that other subunits required for the levamisolesensitive nAChR (Fleming et al 1997;Culetto et al 2004) are not required for EHC suggests that UNC-63 is acting in a different receptor to mediate EHC. We tested the only additional receptor currently known to include the UNC-63 subunit, the neuronal ACR-2 receptor (Jospin et al 2009;Petrash et al 2013), and found that loss of that receptor, through loss of function in the acr-2 gene, did not alter sensitivity to EHC. These results suggest that UNC-63 is likely to act in an as yet unidentified receptor(s) to mediate EHC.…”

Section: Cholinergic Signalingmentioning

confidence: 99%

“…We tested the only additional receptor currently known to include the UNC-63 subunit, the neuronal ACR-2 receptor (Jospin et al 2009;Petrash et al 2013), and found that loss of that receptor, through loss of function in the acr-2 gene, did not alter sensitivity to EHC. These results suggest that UNC-63 is likely to act in an as yet unidentified receptor(s) to mediate EHC.…”

Section: Cholinergic Signalingmentioning

confidence: 99%

“…Instead, these data suggest the involvement of the UNC-63 subunit in a different receptor(s). One likely candidate was the neuronal ACR-2 receptor (ACR-2R), which has been shown to require UNC-63 and UNC-38 subunits (Jospin et al 2009) and is expressed in cholinergic motorneurons (Petrash et al 2013). Loss of function of the acr-2 gene eliminates the ACR-2R, so we tested acr-2(ok1887) for EHC, with the idea that if UNC-63 were acting in the ACR-2R to mediate EHC, then loss of ACR-2R should mimic the unc-63(lf) for this phenotype.…”

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confidence: 99%

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A Novel Cholinergic Action of Alcohol and the Development of Tolerance to That Effect inCaenorhabditis elegans

et al. 2014

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Understanding the genes and mechanisms involved in acute alcohol responses has the potential to allow us to predict an individual's predisposition to developing an alcohol use disorder. To better understand the molecular pathways involved in the activating effects of alcohol and the acute functional tolerance that can develop to such effects, we characterized a novel ethanolinduced hypercontraction response displayed by Caenorhabditis elegans. We compared body size of animals prior to and during ethanol treatment and showed that acute exposure to ethanol produced a concentration-dependent decrease in size followed by recovery to their untreated size by 40 min despite continuous treatment. An increase in cholinergic signaling, leading to muscle hypercontraction, is implicated in this effect because pretreatment with mecamylamine, a nicotinic acetylcholine receptor (nAChR) antagonist, blocked ethanol-induced hypercontraction, as did mutations causing defects in cholinergic signaling (cha-1 and unc-17). Analysis of mutations affecting specific subunits of nAChRs excluded a role for the ACR-2R, the ACR-16R, and the levamisole-sensitive AChR and indicated that this excitation effect is dependent on an uncharacterized nAChR that contains the UNC-63 a-subunit. We performed a forward genetic screen and identified eg200, a mutation that affects a conserved glycine in EAT-6, the a-subunit of the Na + /K + ATPase. The eat-6(eg200) mutant fails to develop tolerance to ethanol-induced hypercontraction and remains contracted for at least 3 hr of continuous ethanol exposure. These data suggest that cholinergic signaling through a specific a-subunit-containing nAChR is involved in ethanol-induced excitation and that tolerance to this ethanol effect is modulated by Na + /K + ATPase function.T HE abuse of alcohol is a cause of significant societal and health-related problems. Despite the common usage of this drug, the molecular underpinnings of alcohol's acute actions on the brain are poorly understood. Alcohol (ethanol) has biphasic behavioral effects in humans and other animals, acting as a stimulant at lower concentrations and as a depressant at higher concentrations. Understanding the molecular nature of these biphasic effects is made difficult by the fact that ethanol interacts with, and alters the function of, many proteins, including neurotransmitter receptors and ion channels (Harris et al. 2008;Spanagel 2009). A commonly suggested class of ethanol targets is ligand-gated ion channels (LGICs), which include NMDA glutamate receptors, and members of a subclass of LGICs, the Cys-loop superfamily, including GABA A , glycine, and nicotinic acetylcholine receptors (nAChRs) (Olsen et al. 2014). Effects on the GABA A and glutamate receptors are hypothesized to play a significant role in the depressant effects of ethanol (Harris et al. 2008). Locomotor activation by low to moderate concentrations of ethanol in rodents is thought to model the euphoric effects of ethanol in humans (Phillips and Shen 1996). Locomotor activat...

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ACR-12 Ionotropic Acetylcholine Receptor Complexes Regulate Inhibitory Motor Neuron Activity inCaenorhabditis elegans

Cited by 54 publications

References 35 publications

Neural circuit rewiring: insights from DD synapse remodeling

Neural circuit rewiring: insights from DD synapse remodeling

Excitatory neurons sculpt GABAergic neuronal connectivity in the C. elegans motor circuit

A Novel Cholinergic Action of Alcohol and the Development of Tolerance to That Effect inCaenorhabditis elegans

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